Dr. Mintz' Blog

I'm Your Cook, Not Your Doctor

2012-01-17T19:03:00.000-08:00

Today on NBC's today show, celebrity chef Paula Deen confirmed she had Type 2 diabetes. She was diagnosed 3 years ago, but only decided to come out today. She also mentioned that she is a paid spokesperson for drug company Novo Nordisk, maker of several diabetes drugs. (Click here to view Al Roker's interview).

When the news started breaking earlier this week, I had mixed emotions about Deen as a spokesperson for diabetes. Blogger and health care marketer Richard Meyer at worldofdtcmarketing.com posted This is a spokesperson for Novo? Deen is of course known for her southern style of cooking, which typically involves very fattening ingredients. At one her restaurants she famously serves a hamburger with bacon and egg on a donut instead of a bun.

Rich correctly asks, "What message does this send to people ? That it’s OK to eat really bad food because diabetes can be treated with Rx drugs ?"

I commented on his blog that if Dean actually changes her ways, and focuses on healthier cooking, providing healthier recipes to her fans and other diabetics, she might actually make the perfect spokesperson. Americans have not been paying attention to what we eat and obesity has now become an epidemic, leading to increasing numbers of patients with type 2 diabetes.

After seeing the Today show video, I remain on the fence. Her interview was not the redemption story I was hoping for. Give journalistic kudos to Al Roker who pressed Deen on whether she had changed her ways or changed her cooking. She responded essentially stating that she has always eaten (and suggested others eat) in moderation, claiming that her weekly cooking show is only 30 days out of a full year and that no one should eat that kind of food every day. According to Deen, when asked a similar line of questions from Oprah, she responded, "I'm your cook, not your doctor."

Deen did state that she and her sons would work to come up with lighter recipes (available on Novo's web site) and recommended people go to their doctor, get tested and "get on a program." On the website diabetes in a new light, Deen does say that she had to give up sweet tea. In fact, rigid diet and exercise programs do not work all that well in reducing weight or improving diabetes, since patients have a hard time sticking to them, so her mantra "I wasn't about to change my life, but I have made simple changes in my life" may have some merit.

However, I believe there is still a difference between promotion of healthy lifestyle and realistic changes in diet and exercise and "everything in moderation" and "it's OK to have that little piece of pie." Paula doesn't have to become the next Richard Simmons or Jillian Michaels, but I would have liked to seen a little more "mea culpa."
I am interested to see how this plays out in the media and in public opinion. This is a terrible disease and the prevalence is getting worse. Ms. Deen has the potential to make a major impact. I hope she takes her spokesperson role seriously.

Nicotine Patches Do Work!

2012-01-11T18:50:00.000-08:00

Here is another example of less than responsible journalism. Both the Wall Street Journal and Fox News report "Quit smoking: A new case for going cold turkey." Even NPR asked Do Nicotine Patches And Gum Help Smokers Quit? Other reports similarly headline with questions regarding the effectiveness of the nicotine patch, which has been a tried and true treatment to help smokers quit. All these reports stem from a study done by researchers at the Harvard School of Public Health and the University of Massachusetts in Boston and published online in the journal Tobacco Control, that found that over a 5-year period, former smokers who used nicotine-replacement products were just as likely to relapse as those who quit on their own.

This is indeed an important study because it shows that relapse rates are high, and nicotine patches may be insufficient to prevent quitters from relapsing. Indeed, other methods should be sought for recent quitters to prevent them from relapsing.

The problem with the way the media is reporting the study is that it is confusing quitting and relapse. Countless studies show that nicotine replacement about doubles the chance that you will successful quit, which is usually defined as not one cigarette for 12 weeks (though better studies use 52 weeks to define quitting). In this study, all the people studied had recently quit.
This study was not measuring whether or not the patch helped these folks quit, but whether people who had quit using the patch were any different than people who had quit without the patch in terms of relapse several years down the road.

People interested in quitting smoking should not be confused by the reports in the media. Nicotine replacement will help you quit. The evidence for using medication (nicotine, bupropion, varenicline) is so strong that the US Surgeon General's guidelines recommends that all smokers (even those at risk to medication side effects such as heart patients and pregnant women) be offered some form of medication, since it is so effective.
Again, the study is an important one because it shows we need to look beyond nicotine replacement to prevent long term relapse. However, the journalists who reported on this study shouldn't have suggested that smokers consider going cold turkey.

Retainer, Concierge and Boutique Medicine are Not the Same Thing

2012-01-05T19:42:00.000-08:00

Health care is in crisis. Reimbursements from insurance companies continue to dwindle, while the expenses of running an office continue to rise. Looming cuts in Medicare are only weeks away, and many physicians may stop taking Medicare. If these cuts go into affect, it is possible that primary care physicians could lose up to 50% of their salary. Just recently CNN reported that some doctors are going bankrupt.

How to fix our health care system is an ongoing debate, but not surprisingly, many physicians have decided not to wait for the government to solve this problem and have taken matters into their own hands. One solution is to simply stop taking insurance altogether. “Cash only” doctors are now commonplace in many major metropolitan areas. Another solution is charging a regular, out of pocket fee (usually) in addition to what insurance will pay for treatment. A version of this model that is becoming popular is called retainer medicine. Sometimes, retainer medicine is referred to a “boutique” or “concierge” even by physicians and others involved in health care (as evidenced by this article in the AMA News, which prompted me to post on this topic).

However, “retainer”, “concierge” and “boutique” are not the same thing. Names are important, and the terms “concierge” and “boutique” tend to have negative connotations. Thus, it is important to describe the differences.

In a retainer model, patients pay a fee (not covered by insurance) to be part of a physician’s practice. This is similar to clients paying a retainer fee to hire a specific lawyer. With reimbursements from insurance companies being so low, the only way an insurance based physician can increase revenues is to increase the volume of patients they see. Unfortunately, when physicians increase the number of patients they see, it leads to rushed patient visits, long waits in the waiting room, and decreased access to physicians including difficulty in getting appointments or responses phone call messages. By accepting a retainer fee, the physician no longer needs to rely on insurance revenue alone, and in fact can decrease the amount of patients he or she sees on a regular basis. This allows for increased access (usually same day or next day appointments and 24/7 phone access) and longer appointment times (usually 30-60 minutes) for patients willing to pay a retainer fee. The typical insurance based primary care physician has about 2500-3000 patients in their practice, and sees about 25 patients a day. The typical retainer physician has about 500 patients and sees only a handful of patients each day. Retainer fees and the amount of access patients get for what they pay vary widely, but the average retainer fee is about $1500 per year.

Some have argued that retainer medicine is unethical because not everyone can afford $1500 a year. First, the typical retainer fee amounts to about $4 a day, which is what many Americans pay (or more) for a Starbucks coffee. Secondly, one could also argue that it is also unethical for insurance based physicians to see complex patients in brief visits and/or not being able to see them in a timely fashion due to lack of access.

Concierge medicine is somewhat different, and in my opinion, should not be used synonymously with retainer medicine.

According to Wikipedia;

“A concierge is an employee who either works in shifts within, or lives on the premises of an apartment building or a hotel and serves guests with duties similar to those of a butler. The term "concierge" evolved from the French Comte Des Cierges, The Keeper of the Candles, who tended to visiting nobles in castles of the medieval era.”

Just like the concierge at a hotel, who can get you good seats at a ticketed event, a reservation at a popular restaurant, or even run an errand; a concierge physician can get you timely appointments with the best specialists, usually doing the scheduling themselves. Many concierge physicians will even accompany patients to procedures or diagnostics tests, and some will even make house calls. Though some retainer practice physicians may perform concierge services (usually the ones charging well over the usual $1500 fee), the terms are not the same. Many retainer physicians will assist in coordinating specialist appointments, but this is as far as they go. In fact, some “cash only” physicians perform concierge services to attract more patients, and some doctors (even insurances based physicians) will charge an extra-fee for some concierge services, such as a house call.

Boutique medicine is also completely different. Again, from Wikipedia:

“A boutique is a small shopping outlet, especially one that specializes in elite and fashionable items such as clothing and jewelry. It can also refer to a specialised firm such as a boutique investment bank or boutique law firm. In the strictest sense of the word, boutiques would be one-of-a-kind but more generally speaking, some chains can be referred to as boutiques if they specialize in particularly stylish offerings.”

I think the key words in this definition are “specilalized” “stylish” and “elite.” The first word is something commonplace in medicine, but the later two words are something usually not associated with medical practice. “Luxury” is also implied in the word “botique.” Thus, in my opinion, a boutique doctor is one that specializes in unique, often luxurious services, that are not offered by others and which will therefore cost a little extra. These services include, but are not limited to, cosmetic procedures (botox, laser hair removal), medical spa services, comprehensive screenings (i.e. body scans), and herbs or supplements. Though both retainer and concierge physicians may provide boutique services, this is generally not the norm. In fact, many insurance based primary care physicians have started to add these services as a way of keeping their practice running. (Ethics could be questioned here as well).

I am not arguing that retainer medicine is the solution for all of our nation’s health care woes. It certainly is not. However, given that it solves some of the issues with 3^rd party payors, is a model that continues to grow, and patients and providers enrolled seem to be very satisfied; it is something that deserves attention. Another model that is garnering some attention is direct access primary care. In this model, patients pay a monthly fee (usually about $70/month) and receive enhanced access and communication as well as primary care and urgent care services. Though the cost is slightly less ($1500/yr vs. $840/yr) and access to your personal may not be 24/7, this is a similar model to the retainer concept. (Proponents have called this retainer medicine for the masses).

Thus, using terms “concierge” and “boutique” that have connotations of elitism, luxury and unnecessary care synonymously with retainer medicine discredits a potentially viable health care model for many Americans. I would request that physicians, policy makers and journalists no longer use these terms as if they were the same.

Statins and Prostate Cancer

2011-12-30T07:31:00.000-08:00

The Wall Street Journal is reporting on a study published in the journal Cancer, and described by Reuters that links statins to reducing the risk of prostate cancer. According to the report:

The researchers found that men who died of prostate cancer were half as likely to have taken a statin at any time, and for any duration, than men in the "control" group. Those with fatal cancers were 63 percent less likely to have ever taken a statin, according to findings published in Cancer.

I would love for statins to reduce the risk of prostate cancer. Readers of this blog know I am relatively pro-statin, in the right patient population. However, this study is too limited to make an actual connection, and I would not recommend taking statins solely for prostate cancer prevention.

What did the researchers do? The looked at the medical records of 380 men who died of prostate cancer and matched them with the records of another 380 men who did not have prostate cancer. They use statistical techniques to adjust for difference such as age, weight and other medications.

What's the problem with the study? First, if the study findings are correct, such a study that uses medical records and then looks back in time can not prove causation. It only proves association. This means that the study doesn't prove that taking a statin will ward off prostate cancer. Rather, the results mean that men who had died of prostate cancer were less likely to take a statin. This is a big difference. There are multiple examples where a confirmed association did not result into a confirmed causation (Vitamin E/C and Folic Acid for preventing heart attacks). In addition, there are many reasons that the association is in fact not correct. Perhaps men who had been diagnosed with prostate cancer chose not to take statins, even if their doctors recommended it, because they were more concerned about the prostate cancer? Perhaps men who did not have prostate cancer were extremely health conscious and were more aggressive about both doing things to prevent cancer (exercise, diet, etc.) as well as being more aggressive about taking statin medications for high cholesterol?

Why this might be true? The only way to truly determine causation is to perform a randomized clinical trial (RCT). Only a RCT can both eliminate some of the confounding variables (i.e. were the men without prostate cancer more aggressive about their overall health) and demonstrate the primary ingredient for causation: that exposure always precedes the outcome. If factor "A" is believed to cause a disease, then it is clear that factor "A" must necessarily always precede the occurrence of the disease.

However, there are two findings from this study that support causation. First, is dose-response relationship. Only the newer, more potent statins showed benefit. Taking a lower potency statin was not protective. The second is biologic plausibility. According to the Reuters report, Dr. Stephen Freedland, who studies prostate cancer at the Duke University Medical Center in Durham, but wasn't involved in the new study was quoted as stating that statins may protect against fatal prostate cancer through their known cholesterol-lowering effects, mentioning that cholesterol is a "key nutrient" for cancer cells, so lower cholesterol levels in the body could prevent more aggressive forms of cancer from developing.

Bottom Line: This study is exciting and will hopefully lead to randomized trials which can prove whether or not taking a statin will prevent prostate cancer. For now, there is very limited evidence to suggest this would actually work, and men should not start taking a statin just to lower their risk of prostate cancer.

More Evidence that Lantus Causes Cancer

2011-12-07T05:42:00.000-08:00

There is a new study reported in Bloomberg this morning that Sanofi’s Lantus Doubled Cancer Risk in Study of Diabetics. The study, which was presented yesterday at the San Antonio Breast Cancer Symposium retrospecitvely evaluated medical records of 23,266 patients in southern Sweden and determined that diabetics who used Lantus had a 2.9-fold greater chance of cancer, while those who took the generic drug metformin had an 8 percent lower risk.

I have previously blogged about this back in 2009 when the first reports surfaced about the link between Lantus and cancer. (See A New Problem With Insulin: Cancer , Lantus Causes Cancer! Why Doesn't Anyone Seem Care? and Lantus and Cancer- A Closer Look Is Not Reassuring )

Back in 2009, when the story broke, the FDA acknowledged the potential link but stated that the data was insufficient and recommended that patients not stop taking Lantus, at least without discussing this with their physicians. They stated that they were "currently reviewing many sources of safety data for Lantus, including these newly published observational studies, data from all completed controlled clinical trials, and information about ongoing controlled clinical trials, to better understand the risk, if any, for cancer associated with use of Lantus." However, we didn't hear much until January, 2011 when they released an update declaring that they had reviewed the four 2009 studies and has "determined that the evidence presented in the studies is inconclusive", and in addition had reviewed results from a 5 year study (sponsored by the makers of Lantus) which did not show an increased risk but was "not specifically designed to evaluate cancer outcomes," concluding, "at this time, FDA has not concluded that Lantus increases the risk of cancer. Our review is ongoing, including review of information from a current clinical trial." With the new study reported today, it will be interesting to see whether the FDA chooses to give and update or reveals and additional information, such as a VA data set they are supposed to be evaluating.

According to the Bloomberg article, a Sanofi study from Sweden, Norway, Finland, Denmark and Scotland is complete and will be submitted to health authorities this month. In addition, U.S. study will be finished in early 2012, while a final report from Europe will come later. All of these studies combined will involve more than a million patients, which will hopefully be enough to give a more conclusive answer.

To be clear, I am not 100% convinced that Lantus causes cancer. However, there is another long acting insulin (Levemir) which has similar efficacy to Lantus, has not been associated with cancer, and has a substantially different affinity for the insulin like growth factor (IGF) receptors that are implicated in the possible connection. Given the mounting evidence of a cancer link with an equally effective product that appears to be safer, I can't see any reason to prescribe Lantus when Levemir is available.

No Medicare "Doc Fix" Could Result in Over 50% Salary Cut to Primary Care Physicians

2011-11-30T19:25:00.000-08:00

Fortunately, the 27% reduction in Medicare payments to physicians that is set to take place in a matter of weeks unless congress acts is getting some press. Fox News published this piece yesterday, as did the Washington Post. Writer Merrill Goozner breaks things down nicely in his article, "Is There a Doctor Fix in the House...and Senate?"

However, one thing that seems to be getting confused in all the media reports is the difference between physician payments and physician salary. A doctor's income is what he takes in (payments) minus expenses or overhead. Physician overhead (staff, office space, electricity, malpractice, equipment,etc.) is very expensive. One of the reasons, but not the only reason, a doctor's overhead is so high is because we need to hire extra staff just to deal with the insurance bureaucracy. (See "Your 10 minute office visit needs 8 people and 45 minutes of work" via KevinMD.) While payments from Medicare to physicians have not really increased over time, overhead has gone up dramatically.

Physicians, patients, and policy makers need to understand that a 27% cut in physician payment will have a far greater impact on physician salary because of this overhead.

An article from the AMA News discussing the issue of the "doc fix" has an interesting table with current payments and proposed payments. Let's say a family physician sees 25 Medicare patients a day, 5 days a week for 50 weeks out of the year. At the current rate of $68.97 per visit, this generates $431,062 in revenue. At 60% overhead of $258,637, this family physician's income would be $172,425 per year. Now any doctor reading this will tell you that 1) no physician would see exclusively Medicare patients because they just don't pay enough (at current rates) to sustain a practice and 2) you can't see 25 Medicare patients in a day because patients 65 and up have multiple medical problems and you simple couldn't see them all in 15-20 minute visits. However, the income is very close to$168,550 which is the average salary for a family physician. Thus, the numbers are good for the purpose of discussing the impact of Medicare cuts on not just payments but salary.

Now, if the 27% Medicare costs go into effect, Medicare will only pay $51.07 for that same visit. Using the same numbers, the revenue generated is only $319,187 (26% decrease in Medicare payments), but the $258,687 in overhead stays the same. This leaves the primary care physicians with a $60,550 annual income. That's a 65% cut in physician salary. Even if my numbers are off, its clearly more than a 27% cut to salary, and much greater than 50%. The bottom line is that if these cuts take place, primary care physicians will certainly stop seeing new Medicare patients, and many will stop taking Medicare patients altogether.Many already have!!!

Now, most pundits seem to think that since seniors vote, and Medicare is a big issue for them, and that the election is less than a year away; Congress will find a way (like they have for the past few years) to find the money to cover the cuts for at least another year. However, I wouldn't be so sure. I would advise anyone who is on Medicare, has a loved on on Medicare, or who plans on having Medicare in the future to call their representatives and ask them to ensure that these payment cuts not go into affect.

Industry Funded Studies

2011-10-24T06:43:00.000-07:00

One of the advantages of being a blogger is the comments, feedback and communications I receive from readers. Though not all of it is positive, many of these interactions with people from across the globe that I do not know has been quite enjoyable for me personally.

One email I received from a reader had to do with industry funded studies. This is not an uncommon concern, and one that frequently shows up on this blog and others. The email encapsulates many people's concerns with industry funded studies.

Dear Dr. Mintz,

I am staring at my computer unable to formulate the words to express my opinion on a very important subject. I do not want to come across as rude, condemning or complaining, yet I am compelled to share with the medical community my honest patient perspective.

I view the medical profession as one of the most respected on earth. But it isn't perfect. As a patient I become very discouraged when I see a medical professional look towards industry funded drug studies to make medical decisions.

Now for the painfully honest part. When I see a Doctor subscribe to "results" from an industry funded drug study, my image of that physician goes to pot in a heartbeat. "How can he/she be so gullible" and "Incompetent" are thoughts that pass through my mind. I quickly lose trust in that physician's ability to make smart decisions in my health care, and the doctor loses my business.

On on the contrary, I asked a physician what he thought about industry funded drug studies, he answered "I ignore them." This doctor won me over in three words.

Obviously it takes excellent academic ability to become a physician, but I look for more than that. I look for wisdom and integrity when choosing a physician.

There is no question that industry studies are biased by nature. The drug company is beholden to its stockholders to increase sales. Therefore, they have a fiduciary obligation to make sure that their research puts their products in the best light. This is not unlike any product in the US where a manufacturer does research stating that people prefer it or it works better than a competitor. Unlike these products, medications are heavily regulated in the United States. Thus, for a medication to get approval or to make any claims, all studies, including ones funded by the industry have to go through the FDA.

Here's the real problem:

Almost all research done on medications is funded by the industry. I would love it if instead of relying on industry sponsored studies, I could rely on non-biased information. However, when it comes to medications, these studies are few and far between. In 2005, the industry spent close to $40 billion dollars on research. Compare this to the entire NIH budget that same year of less than $30 billion. Also, understand that the NIH spends very little money on actual drug studies. They focus more on finding a cure to cancer, not whether expensive medicine X is just as good as the older generic medication.

When I want to know whether to buy product X vs. product Y, I can go to an independent source such as Consumer Reports, which does their own, independent research. There is really no such independent source for drug information. In fact, prescription drugs is one of the only areas that Consumer Reports does not do their own research. All their recommendations on which medicine is "right for you" come from drug company sponsored studies.
If we ignored all industry funded studies, we be ignoring most of the data. In addition, since these studies are heavily regulated, we would be ignoring mainly good, helpful data, even if biased. The simple alternative is to fund the NIH or similar organization equally to the drug companies in order to do independent research. Of course this would likely require significant government spending, which is likely a non-starter.

The good news is that independent comparisons of treatment, called comparative effective research, are starting to be done, and (whether you like health care reform or not), there is funding for this research in the Affordable Care Act. Unfortunately, this funding is not nearly enough to compete with the drug companies. Thus, unless you are willing to pay considerably more in taxes or drop some needed services, physicians and patients still need to rely on industry funded research. Many studies from the industry are actually quite good and useful, though, because of inherent bias, should always be looked at with a skeptical eye.

PSA: To Screen or Not to Screen

2011-10-09T09:51:00.000-07:00

There has been much confusion/concern/media attention since the recent announcement (see the NY Times article US Panel Says No to Prostate Screening for Healthy Men) that PSA tesing was no longer recommended by the US Preventative Services Task Force. (Here's the full version of their draft recommendation.) There are many responses out there (Tara Parker Pope's Answering Questions about the PSA test is a good one), but I believe there is still more to say on the issue.

Before answering the question regarding whether we should follow the USPSTF's new recommendation, please consider...

1. The USPSTF is the same group that says

-Women shouldn't get mammograms before 50

- Recommends against teaching self-breast examination

-States that screening for testicular cancer is harmful

-Only recommends screening for diabetes in patients with high blood pressure

-Recommends against screening for depression for most primary care doctors

(I am not stating that I necessarily disagree with these recommendations. However, it is important to understand where USPSTF is coming from when considering their PSA recommendation).

2. Prostate cancer is still a leading cancer killer for men in the US.

From NY Times:

One in six men in the United States will eventually be found to have prostate cancer, making it the second most common form of cancer in men after skin cancer. An estimated 32,050 men died of prostate cancer last year and 217,730 men received the diagnosis.

The new recommendations come from findings of two large studies. One in the US that showed no benefit in saving lives, and one in Europe that showed only some benefit. The US study have some major limitations, including that many of the men in the placebo/no-screening group actually got screened, so I will focus on the European study.

The European Randomized Study of Screening for Prostate Cancer looked at close to 200,000 men between 50-74 for about 9 years. Not surprisingly they found almost double the rate of prostate cancer in the screened group compared to the non-screened group (8.2% vs. 4.8%). More importantly, they reduced the rate of death by about 20%. Unfortunately, most of the men treated for prostate cancer did not benefit. They found that for every 1410 screened, there were 48 additional cases of prostate cancer found, that if treated would only prevent one death from prostate cancer. In other words, if you are treated for prostate cancer, there's only about 1/50 chance it will save your life. Now, if the treatment were without side effects, then besides costs, there would be no reason not to screen. (My friend Dr. Stewart Segal in his post PSA Confusion suggests covert rationing is one motivation behind the USPSTF's recommendation). The problem is that there are side effects with treatment, and not inconsequential ones. There is about a 20-30% chance of impotence, incontinence or both.

However, there seems to be two things not discussed in any of the reports:

1. Though the writers of the guideline seem to give value/risk of the harms of treatment, they do not address the potential benefits of the piece of mind from a negative screen. In the European study, over 90% of men had a negative screening over the course of almost a decade. In other words, the vast majority of men screened had the piece of mind knowing that probably didn't have to worry about prostate cancer. (There is also additional evidence that men 65 and older with a very low PSA will likely never get prostate cancer, and screening should be stopped).

2. Just because you are diagnosed with prostate cancer, doesn't mean you need to treat it. Given the complications as a result of prostate cancer treatment, and the fact that prostate cancer tends to progress slowly, especially after the first year, watchful waiting is a reasonable approach. If in fact, if the cancer remains stable, treatment can be deferred potentially indefinitely. However, without the diagnosis, watchful waiting can not occur.

Bottom Line: There is no right answer for everyone. Patients, in consultation with their doctor, need to make a decision that's right for them. If you are a healthy person, with no cancer risks, worry about side effects and complications of medical treatment, and realize that there's a 98% chance that screening for prostate cancer will not save your life, you should not get a PSA test or prostate exam. However, if you are someone that is very fearful of cancer, would have substantial piece of mind if you were one of the 90% of men that tested negative, and if you did get diagnosed with prostate cancer are willing risk treatment knowing there is only a 1/50 chance it will save your life, but about a 20-30% chance you will get side effects from treatment, then you should get tested.

Is meaningful use the right incentive to get physician's to use EMR's?

2011-09-14T17:56:00.000-07:00

Before I took over one of the classes that now teach at the medical school, I asked students why the value of that class was so low. One of the reasons they gave was that it was so hard to do well in the class, and there were so many other things to study, students only put in enough effort to pass. In other words, incentives are only good if they are both valued and attainable.

As this related to Electronic Medical Records (EMR's), achieving meaningful use is not easy. The technology for clinical decision support (a requirement) is not quite ready for prime time. Nor is there an easy way to share parts of the EMR with patients. In a study of almost 600 docs who had been using EMR's, most were confident that they would qualify for meaningful use and get bonuses for doing so. However, the survey also found that the majority of these physicians would not meet some of the criteria. Thus, though the financial incentive seems nice, the path to getting these incentive may be so unattainable that physicians won't waste the effort or expense.

More importantly, some of the "stuff" that's meaningful in meaningful use, may not have value for physicians. Policy makers that developed these criteria were understandably thinking on a population level (lowering blood sugar in a population of diabetics). However, physicians are used to dealing with patients one on one.

A recent survey of EMR using physicians was done over at Software Advice regarding the advantages of using EMR's. Granted 50 respondents may not accurately generalize to most physicians; however, some of the results are telling. What do doctors like about EMR's? Greater accessibility of charts, easier to read notes, more accurate patient information, and improved coordination of care by having the ability to share data. As a user of EMR's for well over a decade, I would concur with these findings. EMR's are far from perfect, but based on these advantages, I could never go back to paper. What "benefits" of EMR's did doctors not see as readily? Improving preventative care, opportunity to participate in pay for performance, improving clinical decision making, and reducing errors/improving patient safety.

Thus, under the current plan to increase EMR use by physicians, the financial incentives may be too hard to achieve and the purported benefits may not be easily perceived. This combination does not bode well for the adoption of EMR's by most physicians. Instead, policy makers might want to consider a different approach. First, rather than create a financial carrot that will be too difficult to achieve for most, use that money to reduce barriers to adopting EMR's in the first place. Second, instead of focusing on the benefits important to policy makers, focus on benefits that are important to physicians, such as making our work easier and more productive. This is important because EMR vendors design their products on what they believe will meet their customer's needs. The first EMR platforms focused on improvements in billing and coding to capture more revenue. Now, vendors are focused on helping physicians achieve meaningful use. If vendors focused on making a physicians work easier and more productive (and policy maker made it easier to adopt these tools), EMR adoption would be much greater than it is now.

Disappointing Results for Crestor

2011-09-02T05:53:00.000-07:00

In my recent post All in for Crestor, I discussed how the SATURN study comparing Crestor to Lipitor was likely a make or break study for AstraZenca's cholesterol pill. As mentioned, because Lipitor will soon go generic in November, AZ needed to give insurance companies a reason to pay for the more expensive branded pill, then the soon to be generic and cheaper version of Lipitor, which has been the number one selling drug in the country.

As reported in Pharmalot's post Disappointing Crestor Results For AstraZeneca (see the official AstraZeneca statement here ), the just released results of SATURN show that the 40mg dose of Crestor was numerically but not statistically significantly better and reducing plaque build up (as measured by % change) as the 80mg dose of Lipitor. As secondary measure, plaque buildup as measured by volume was statistically significant, but since this was not the primary outcome of the study, it is likely enough for insurers to give Crestor a favorable status on their formulary lists.

Bottom Line: Crestor is a great drug. It reduces LDL better than Lipitor. We know that from outcome studies of all statins, that the lower the LDL with a statin, the more you decrease heart attacks and strokes. In addition, despite it's potency, it has very good tolerability. Certain patients that might need 80mg of Lipitor, might not be able to tolerate side effects at that high of a dose, and might end up doing better on 20mg or 40mg of Crestor. That said, starting in 2012, unless AZ cuts the price on Crestor drastically, it may be a challenge to get the prescription approved for patients.

All In For Crestor

2011-08-16T08:26:00.000-07:00

The American Heart Association will be holding its annual meeting this November. Cardiobrief.org just posted the announced "late-breaking" clinical trials. These are the big name trials that usually grab a lot of headlines. One of the trials is the AIM-HIGH trial which showed that Niacian didn't really do much in patients whose bad cholesterol or LDL was controlled with a statin (see my post What to do about Niacin? )
Another very important study will also be presented that same November 15th, 2011: Comparison of the Progression of Coronary Atherosclerosis for Two High Efficacy Statin Regimens with Different HDL Effects: SATURN Study Results. The SATURN study is the Astra Zeneca (makers of Crestor) study comparing high dose Crestor (40mg) with high dose Lipitor (80mg).

Patients in the SATURN study will have known cardiac disease as indicated by a need for coronary angiography (angiogram) and angiographic evidence of coronary disease. The main end point is is IVUS-assessed change in the percent atheroma volume in a >40-mm segment of a single coronary artery; which is a "doctor" way of saying they are going to look for plaque build up in the artery. This is the same end point used in the famous (or infamous) ENHANCE trial which showed that adding Zetia to simvastatin (zetia + simvastatin = Vytorin) did absolutely nothing to plaque build up ( Vytorin and Zetia: What to do now? )

What's interesting about SATURN is that the LDL lowering properties of the highest doses of Crestor and Lipitor are about the same. However, at those doses Crestor raises the HDL or good cholesterol by about 8% where Lipitor only raises HDL by 3%. Other studies have shown that plaque build up in the arteries (atherosclerosis) that causes heart attacks and strokes, is not just about LDL, but also about HDL. Other studies looking at high doses of Crestor when compared to placebo show that it can prevent plaque build up and possibly even lead to regression. The Lipitor data on this is less robust.

The timing of the results at the AHA is particularly interesting, since it will coincide with Lipitor going generic. Zocor or simvastatin has been generic for a while, and works well in many patients. However, patients requiring more aggressive reduction in their cholesterol will not meet their goals on simvastatin and high dose simvastatin is associated with side effects, which prompted a recent FDA warning. (See Don't Take High Dose Simvastatin). Thus, the need for a generic potent statin like Lipitor is huge. However, this could mean that insurers will make it very, very difficult for patients to get Crestor. UNLESS......... SATURN proves that high dose Crestor compared to high dose Lipitor significant reduces plaque build up in high risk patients.
Therefore, the SATURN trial is really a huge gamble for Astra Zeneca. When Merck's ENHANCE trial showed that Vytorin didn't really do more than the generic statin, prescribing rates dropped precipitously. Crestor likely faces the same fate is SATURN turns out to be a negative study.

Why OTC Lipitor is a Bad Idea

2011-08-04T06:11:00.000-07:00

As reported by the Wall Street Journal, Pfizer, the maker of one the best selling drugs ever, is trying to get the FDA to approve an Over the Counter (OTC) version of their blockbuster Lipitor, not coincidentally on the eve of Lipitor going generic.
Readers of this blog know that I am a big proponent of cholesterol lowering medications like Lipitor (statins) for patients at moderate to high risk of cardiovascular disease. In particular, I am a fan of the more potent statins like Lipitor and Crestor, because of their increased efficacy with fewer side effects (see Don't Take High Dose Simvastatin). Finally having a generic version available of Lipitor will be a great thing for many patients.

That said, making Lipitor OTC is a bad move. First, there is a difference between medications like Prilosec and Claritin that have gone over the counter and Lipitor. Diagnosis for GERD and allergic rhinitis for which those medications respectively treat are made mostly on symptoms alone. Patients don't need to go to medical school to suspect that they may suffer from heart burn or allergies. Starting treatment without seeing a physician is actually medically sound because more often then not the medications will relieve symptoms avoiding a physician office visit. In contrast, starting a patient on a statin is much more tricky. Patients need to know their individual risk for cardiovascular disease. Though there are tools available online to determine this (I use the NIH's risk calculator daily in my clinic), determining individual risk of disease, benefit of taking a medication and weighing this against potential side effects is best decided by a discussion between a doctor and patient. Secondly, before starting a statin medication, one needs to know their cholesterol levels. Though there are other methods (health fairs, work screenings) of determining cholesterol levels, getting a blood test usually requires a visit to the doctor's office. In addition, follow up blood work (checking for medication efficacy, liver side effects) is warranted after starting treatment. Thus, the benefit of having a medication OTC is negated. Finally, Claritin and Prilosec are very safe. They are as safe or safer then other OTC medications. Lipitor is also very safe, but is associated with rare, but serious side effects. Taking Lipitor OTC without consultation with a physician creates the risks of patients developing these side effects without proper warnings and therefore potentially worse outcomes if attention is not sought.

The second main reason that OTC Lipitor is a bad idea is that it will hurt more patients than it will help. The reason for this is that when a medication goes OTC, insurance companies usually will not pay for them. Now that Allegra is over the counter, it is virtually impossible for any of my patients to get a prescription version antihistamine. Though they can easily get this OTC, not having a prescription means they need to pay for it out of pocket. The cost of an OTC medication, even if the generic OTC version is used, is generally more than the co-pay for a generic prescription. It is unlikely that generic Lipitor will make the $4 Walmart or Target list, but after six month, the co-pay for generic Lipitor would still likely cost a lot less for most patients then paying for OTC Lipitor out-of-pocket.

Bottom Line: The reason why Pfizer wants Lipitor OTC is for one reason: to make more money. They can argue that cardiovascular disease is the number one killer in the US, and by having Lipitor OTC, it will be available to more patients. However, because statins require blood work and medical consultations, the risk of harm to patients outweighs the potential benefits of greater availability. In addition, this will result in cost-shifting to patients in order to boost Pfizer's profits. Hopefully, the FDA will say what they said when Merk tried to pull this off: "No."

Chantix should not be withdrawn.

2011-07-05T09:13:00.000-07:00

Despite the rising rates of obesity, smoking is still the single leading cause of preventable death in the US. Quitting smoking is very difficult because one needs to address both the behavioral and pharmacologic aspects of nicotine addiction Though other agents are available, Chantix or varenicline is the most effective agent to assist in smoking cessation. This has been proven in several large, randomized clinical controlled trials (RCT's). RCT's are the gold standard when it comes to scientific proof. (More on that in a minute).

Chantix is not without issues. The main side effect is nausea, which about 30% of users will get. It is usually mild and usually goes away, though a small percent of people will not tolerate this. The more recent concern with Chantix was exacerbations of neuropsychiatric symptoms: depression, anxiety, and suicidal ideation. These side effects were not seen in many of the initial studies, but in later on via reports by doctors and patients after the drug was on the market. This method is called post-market surveillance. Post-market surveillance is critical in determining drug safety, because rare but serious side effects may not be seen when you only study thousands not millions of patients. However, unlike RCT's , proving cause and effect can not be determined. In regards to psychiatric symptoms, in the original studies that the Pfizer submitted to the FDA, Chantix had few interactions and did not show any. However, because Pfizer compared Chantix to bupropion (the only other pill indicated for smoking cessation, but also used for depression), patients with mental illness were purposely excluded from the study. (See more about this in Where's the Good News about Chantix? and More FDA warnings should not be cause for worry.) In fact, since these warnings first appeared, further studies seem to indicate that just stopping smoking, not necessarily Chantix, can cause these problems. Furthermore, warnings were not just added to Chantix but also to bupropion. Regardless or whether symptoms like depression or even suicidal thoughts is linked to Chantix or stopping smoking, doctors and patients should be aware of this concern for any patient quitting tobacco.

Now we have a new concern regarding Chantix causing cardiovascular events. The initial concern was raised by the FDA in their review of a study of 700 patients with known cardiovascular disease randomized to Chantix or placebo. Though Chantix was far more effective in helping these patients with known heart disease quit tobacco, there was a small number of increased cardiovascular events, more in the Chantix group than placebo. The total number of events was 28 in the Chantix group vs. 17 in the placebo. The study was not designed to show whether or not this number was statistically significant (was really true), but the FDA added a warning to Chantix' label.

However, a new study raises questions about Chantix and people without heart disease. This is being blasted all over the media. The Wall Street Journal reports "Drug Tied to Heart Risks." The New York Times reports "Study Links Smoking Drug to Cardiovascular Problems." ABC News states "Chantix: Quit Smoking, But Risk Your Heart?" All of them have similar language to the ABC news site stating:

Study authors looked at 14 past studies of Chantix and found that overall, people on the drug had a 72 percent increased risk of being hospitalized with a heart attack or other serious heart problems when compared with those taking a placebo.

That seems pretty bad! Unless, of course, you look at the actual data. The new study is a meta-analysis of studies looking at patients on Chantix without cardiovascular disease. The study is from the Canadian Medical Association Journal. They looked at data from 14 RCT's 8216 participants. They found that Chantix was associated with a significantly increased risk of serious adverse cardiovascular events compared with placebo on 1.06% [52/4908] in varenicline group compared to 0.82% [27/3308] in placebo group. In other words, the absolute difference between Chantix and placebo is 0.24% or 24/10,000. This sounds a lot less scary than 72% increase (relative increase) being reported in the media. It is also very, very important to note that the technique used to derive these numbers is a statistical technique, a meta-analysis, which is not nearly as rigorous as an RCT. Meta-analysis are designed to ask questions, not to answer them. ( I have blogged previously about the pros and cons of meta-analysis). Furthermore, even patients without a history of cardiovascular disease who smoke, have a risk for cardiovascular disease, which is why they need to stop in the first place.

Bottom Line: One must always question 1) the results of a meta-analysis because it has many limitations and 2) any non-RCT, especially a meta-analysis, with a very small absolute risk (i.e. 0.24%) especially if the authors/journalists are trumpeting a large relative risk (i.e. 72%) and also 3) take into account the context of the situation, i.e. the single best agent we have available for the leading preventable cause of death in the United States, might possibly have an associated very small increase in heart disease in smokers that will likely have a much greater risk of heart disease if they don't stop smoking. While I agree more research is needed, and warnings about a possibly increased cardiovascular risk are not inappropriate, pulling Chantix from the market would be a huge mistake.

Paying For Your Time

2011-07-01T18:28:00.000-07:00

There has been a lot of Internet/Twitter buzz regarding a recent CNN article "Would your doctor pay for wasted time?" by Elizabeth Cohen. The premise of the article is that a patient's time is valuable, and if the doctor keeps a patient waiting for longer than anticipated, it should be the doctor that pays the patient, since the patient's time is valuable too. She describes the story of patient Elaine Farstad waited over two hours to see her physician.

"I decided to bill the doctor," she says. "If you waste my time, you've bought my time."

Farstad mailed an invoice to her doctor based on her own hourly wage, and eventually received a $100 check in the mail.

As mentioned, this story has received considerable attention. Over at the blog Survivor: Pediatrics , Brandon Betancourt humorously counters "Why not bill everybody that wastes our time?" including the movie theaters that make us sit through commercials and previews before the movie we came to see, or even Disney for waiting in those long lines.

However, the issue of why patients have to wait is an important one. Most patients recognize that emergencies do come up in medicine, which often causes doctors to run behind schedule. However, medical emergencies are not the main reason why patients spend long waits in doctor's waiting rooms. The answer can be found in a study published last year and discussed in the New York Times "Study Shows ‘Invisible’ Burden of Family Doctors." Primary care physicians do a lot more during their day than just see patients. However, they only get paid for seeing patients. The actual study, published in the New England Journal of Medicine measured exactly what a group of family physicians did in a given day.

Family doctors are paid mainly for each visit by patients to their offices, typically about $70 a visit. In the practice in Philadelphia covered by the study, each full-time doctor had an average of 18 patient visits a day.

But each doctor also made 24 telephone calls a day to patients, specialists and others. And every day, each doctor wrote 12 drug prescriptions, read 20 laboratory reports, examined 14 consultation reports from specialists, reviewed 11 X-ray and other imaging reports, and wrote and sent 17 e-mail messages interpreting test results, consulting with other doctors or advising patients.

All of this unpaid work takes an incredible amount of time. Also, assuming that the doctors were collecting 100% of their $70 per visit, at 18 visits a day, with 60% overhead (often more for doctors), the doctor only takes home about $120,000 a year in salary. Now that seems like a pretty good salary, and is certainly much more than most Americans make. However, it is far lower than many other professionals with equal or less training (lawyers, accountants, dentists, college professors, etc.) and also doesn't take into account the enormous debt that medical students accumulate (in some cases close to $200,000 at graduation, adding up to well over $1 million if paid over the course of a typical loan). This is why our medical students are not going into primary care.

All this work can't be done in a given day, and the doctor can't see fewer patients to squeeze in this work because it will lower her salary even further. Another way to put this is that the doctor's time is valuable too, but she isn't get paid for her time. The doctor is getting less than what's it worth from the insurance companies for actually seeing patients and getting nothing from insurance for anything that's not face to face.

Thus, the doctor who is trying to see too many patients in too little time while simultaneously trying to get all the phone calls, lab results, etc. is going to run late. In my practice, with the exception of the first patient of a morning or afternoon session, I start each patient conversation with, "I am so sorry to keep you waiting." There is only so much that can be accomplished in 15 minutes. Primary care physicians who need to manage multiple complex medical issues have a choice: be good or be on time. I choose to do the best job I can, which causes most of my patients to wait much longer than any of them should.

One solution to the problem is to have insurers properly reimburse primary care physicians for all the work that they do. Unfortunately, regardless of who gets elected in 2012, this seems unlikely to happen. Another solution is to get the insurance companies out of the mix all together. This alternative solution is already starting to happen. Retainer or concierge practices, which charge an annual fee (on average $1500/year) allowing doctors to have a very small number of patients who have instant access and no wait times, are gaining in popularity. Some have suggested that this is one solution for the primary care crisis.

However, many patients can not afford high retainer fees nor necessarily need this level or service. For these patients, another solution is direct access primary care. Direct access primary care works more like a gym membership, where you pay a monthly fee for all of your basic primary care needs. You can use your direct access primary care provider as little or as much as needed. Qliance in Seattle, charges about $75/month.

There are a variety of other models that improve patient and physician satisfaction, and likely the actual quality of care. However, the key ingredient in all of these models is cutting out the insurance companies to save money, hassle and overhead costs; and collecting money directly from patients to enhance revenue. This combination allows primary care physicians to spend more time with patients, have increased access, and subsequently low to no waiting for patients.

Bottom Line: The current insurance based system keeps primary care physicians on a treadmill, usually forcing them to choose quality of care over patient convenience. Though all patients deserve high quality, patient centered care that is convenient as well, the solution of higher reimbursements and decreased hassles for primary care physicians does not appear to be happening any time soon. Thus, as a patient, you have a choice. If your time is valuable, then you are going to have to pay extra for primary care services. If you choose to (or are only able to) rely on health insurance premiums and co-pays to cover the cost of your care, you should expect to wait. Expect to wait to get a timely appointment with your doctor. Expect to wait for the phone call with results of your recent tests. And, of course, expect to wait in your doctor's waiting room.

Actos Causes Bladder Cancer. Maybe We Should Have Kept Avandia?

2011-06-11T08:52:00.000-07:00

Both Germany and France have now suspended the marketing of Actos (pioglitazone) due to concerns of a link between Actos and bladder cancer. Though we have known about bladder cancer concerns for some time, these recent concerns about the bladder cancer link stem from a recent report analyzing the FDA's Adverse Event Reporting System (AERS), which found that 93 cases of cancer were recorded between 2004 and 2009 in patients treated with antidiabetic drugs of which 31 patients were treated with pioglitazone, representing a statistically significant increased risk of bladder cancer (ROR 4.30, 95% CI 2.82-6.52; p<0.0001). Interestingly, the FDA announced that it was going to look into the link between Actos and bladder cancer only a few days before it made it's final decision on what to do with Avandia (as if they didn't know about the Actos cancer risk before the July 2010 advisory board).

Despite the many things you have heard about Avandia, back in July 2010, the FDA decided to severely restrict the use of Avandia for three reasons:
1. Despite limited and conflicting data, there seemed to be a signal of myocardial infarction for patients taking Avandia.
2. The one study proving Avandia's safety, RECORD (see here for more details) was discredited by FDA scientists due to potential reporting errors.
3. The advisers on the panel felt strongly that despite limited and conflicting evidence, the signal was enough to be concerned AND because Actos (similar drug in same class) did not seem to show this signal, why would doctors ever want to prescribe Avandia?

I have blogged extensively about Nissen's meta-analysis that triggered the whole Avandia scare. Meta-analysis have major limitations. Another group of researchers using the same data as Nissen's with different statistical techniques concluded that Avandia did not cause heart attacks. Large, randomized trials are the only way to determine certainty, and all available large trials (DREAM, ADOPT, ACCORD, etc.) with rosiglitazone showed no heart attack risk. As mentioned above, the one study designed to definitively show whether or not Avandia led to cardiovascular risk (RECORD, which showed that Avandia did not cause cardiovascular risk, and in fact surpasses the FDA's standard for cardiovascular safety) was harshly criticized by those within the FDA that wanted to see Avandia pulled from the market. Specifically, the FDA found that GSK had some errors in reporting the results of RECORD. Though these types of errors are not uncommon in very large trials, and likely won't affect the overall results of the study, nonetheless, the deserve looking into. However, the FDA promised to do a complete independent analysis of the RECORD results; a promise it has yet to deliver on.

The main issue here is #3: Actos appears to be safe, so let's dump Avandia. (Interestingly, independent cardiologists analyzed all the data and did not find a conclusive difference in cardiovascular risk between Actos and Avandia). Here is the full transcript of the advisory board. Since it is a very difficult document to read through, I have pasted some of the direct quotes below from some of the advisers who voted to either remove Avandia from the market or severely restrict its use. Based on these quotes, I feel pretty strongly that had the advisers known about Actos' bladder cancer risk, that they may have voted very, very differently. However, the FDA did know about the association between Actos and bladder cancer. They just chose not to mention it! In fact, when one adviser brought up the question at the July advisory board, the FDA only briefly mentioned this and discussed it more as a class effect also seen with dual PPAR agonists.

Avandia and Actos help diabetics use their own insulin better by hitting a receptor called PPAR. There are three main PPAR receptors: Alpha, Gamma and Delta. We don't know a whole lot about delta, but PPAR Gamma works on glucose, and PPAR alpha affects cholesterol. Fibrates like gemfibrozil, which lower triglycerides and raise HDL or good cholesterol are PPAR alpha agonists. Dual PPAR agonists were drugs that pharma were trying to develop that hit both alpha and gamma in order to help both with lipids and glucose. They have not been able to make it to market due to safety concerns (raised by, guess who??? Dr. Nissen). One of the differences between Actos and Avandia, is that Actos has a higher affinity for the PPAR alpha receptor, which is why it likely does a better job on raising HDL and lowering triglycerides than Avandia. Some have hypothesized that this might be the reason why Actos might not have the same cardiovascular issues as Avandia (though this has yet to be shown). If in fact, as stated during the FDA meeting (I am not aware that this data is published) that the bladder cancer risk was seen in both Actos and the dual PPAR agonists. Bladder cancer has not been seen with Avandia. In other words, the evidence (both available and suggested by FDA quotes that are public record) suggest that Actos may have more of a bladder cancer risk than Avandia.

Why the FDA in discussing to keep Avandia on the market would not extensively discuss the concerns of bladder cancer with Actos, paired with the weak and controversial data showing Avandia's cardiovascular risk and effort to discredit GSK's study proving Avandia's safety leads me to believe that the FDA's attack on Avandia was very much politically motivated. Scientists look at all the available data and weigh the risks and benefits of all options before making a conclusion. It is clear to me that the FDA's decision on severely restricting Avandia was more political then science. Based on the currently available data which now include bladder cancer risk, Avandia may actually be a better choice than Actos, but the FDA's restriction will essentially prevent any doctor from being able to prescribe Avandia after November.

Select quotes from advisers who voted to voted to either remove Avandia from the market or severely restrict its use:
DR. SCHAMBELAN: This is Morrie Schambelan. I voted E. (remove Avandia from the market) . I was one of the brain-dead kangaroos last time (meeting in 2007) who was on the fence, largely because I did see a signal for harm. I was led at that time by the comparison to active comparators, which I think is much more relevant to me than placebo. I wasn't swayed by the pioglitazone data that were presented at that time because they were pretty preliminary. I was much more persuaded this time, including Dr. Graham's analysis. I feel that pioglitazone is a perfectly acceptable alternative.

DR. SAVAGE: Peter Savage. I voted D (keep on the market with restrictions) I was also oscillating between D and E because I think that the evidence of potential harm associated with rosiglitazone is stronger now than it was in 2007. And very importantly, the evidence about pioglitazone is substantially greater than what we saw treat in 2007.

DR. FLEMING: Fleming. I voted E. My main sense about this is really explained in my answer to question number 7. There's very concerning data about safety with rosiglitazone. It's not definitive, but if TIDE is to provide that, we have many years before we're going to get that insight. We do have an alternative, pioglitazone, for which there is considerably strong safety experience. So I come down to, then, what is the continued role for rosiglitazone?

DR. THOMAS: Abraham Thomas. I voted E. The scientist in me says we should always seek the truth. But this isn't an NIH study section. This isn't the review of a journal for publication. Really, what this is is an intersection, as someone mentioned at lunch, between public policy and science. And when we look at it that way, we can't always have the absolute truth to make a decision. We have other classes that are available that we never had before for the treatment of diabetes. And if rosiglitazone was removed from the market, we still have another TZD, what has had a trial that does demonstrate no increased cardiovascular mortality, no increased cardiovascular events, in PROactive.

Don't Take High Dose Simvastatin!

2011-06-08T14:00:00.000-07:00

Today the FDA just announced a new warning on the highest dose of simvastatin, the most popular cholesterol medication prescription in the country. They have issued this warning because "the highest approved dose--80 milligram (mg)--has been associated with an elevated risk of muscle injury or myopathy, particularly during the first 12 months of use."
The current recommendation is not to start simvastatin at 80mg and only to continue taking the 80mg if you "have been taking this dose for 12 months or more and have not experienced any muscle toxicity. It should not be prescribed to new patients.

First, why is this announcement so important.

As Forbes' Matthew Herper points out in A Snapshot Of The Cholesterol Drug Market, though Lipitor is the biggest selling drug in terms of dollars, generic simvastatin is actually the most commonly prescribed cholesterol lowering medication. As you can see from the graph below (viewed much better on the Forbes site), once Zocor became available as generic simvastatin, it became the most popular statin written (blue line) whereas Lipitor (red line) prescriptions continue to tumble. Over time, insurance companies have made it more and more difficult to write for any branded statin by increasing co-pays for patients or increasing hurdles to get prescriptions approved.

In fact, simvastatin makes sense for many patients. Most data suggest that benefit is derived from statins when they reach about a 30% reduction in bad cholesterol, or LDL. The folks at the NIH's NHLBI have evaluated the efficacy of all the available statins (see below) and you can see that most statins will achieve that goal at various doses. For example 10mg of atorvastatin (Lipitor), 20-40mg of simvastatin, and 5mg of rosuvastatin (Crestor) all lower LDL cholesterol by about the same amount. Thus, if you just need a 30% reduction in LDL, you should be fine with the generic. Problem is that many patients need more than that amount of reduction. Thus, if you want to stick to a generic, you would have to go to 80mg of simvastatin.

Now one might thing that the stronger, more potent the statin, the more likely it is to cause side effects. Turns out the opposite is true. The graph below shows that when plotting LDL reduction against number of patients developing myopathy (what the FDA is concerned about), it seems like the more potent statins (Crestor, Lipitor) not only lower cholesterol better, but have a lower risk of myopathy. Myopathy is pretty uncommon, usually only about 1/10,000 or 0.01%. Looking at both Lipitor and Crestor, you can see as the dose goes up (10, 20, 40, 80) the percent of reduction of LDL continues to improve, but rate of myopathy is pretty much the same except for a slight bump at the 80mg dose of Lipitor. (Though not on the graph, you can see why the 80 mg dose of Crestor wasn't approved, because at that dose there was significant myopathy). However, when you jump from 40-80 mg of simvastatin, the LDL only goes up a few points, but the rate of myopathy skyrockets to over 1% (that's 1/100 instead of 1/10,000). Finally, you can why cerivastatin or Baycol was pulled from the market. It was pretty weak at lowering LDL, but had up to 2% incidence of myopathy at the higher doses.

The good news is that Lipitor will go generic in only a few months. When that happens, I am sure that the graph above will change drastically. All Lipitor scripts will likely go to the generic medication and probably many of the simvastatin prescriptions will also switch to generic atorvastin, since it is a better statin (more potent, fewer side effects). Crestor is another option (most effective, fewest side effects), but will not go generic for a while. The other thing to note is that Pfizer, who is about to lose Lipitor, is trying to get as much business as it can by offering patient coupons, so that (as long as you are not on Medicare part D or Medicaid) a prescription of Lipitor will only cost you $4 until it goes generic.

Bottom Line: All statins are not created equal and generic is not always best. If you are on Simvastatin 80mg, you should seriously discuss with your doctor about switching. In fact, if you are on simvastatin at any dose and not on Medicare part D or Medicaid, but have commercial insurance, you should consider asking your doctor about switching to Lipitor with the $4 coupon (you may actually save money by NOT taking the generic) until it too goes generic.

What to do about Niacin?

2011-06-04T07:13:00.000-07:00

I have been getting a lot of questions regarding the use of Niacin since the media recently reported that the NIH had stopped their AIM-HIGH study. AIM-HIGH was designed to see if adding Niacin to patients on a statin who still had low HDL and high triglycerides would improve cardiovascular outcomes (heart attacks, strokes). Though we know that high triglycerides and low HDL are both strongly associated with heart disease, that Niacin will raise HDL and lower triglycerides and even few early studies did show raising the HDL with Niacin did work; this large, randomized NIH sponsored showed no evidence of improvement. Though the actual data from the study has not been released, we do know that the NIH stopped the study a year early because there was no benefit seen and possibly some harm in the form of excess stroke. One possibility is that patients were taking statins at doses that lowered their LDL to very aggressive levels (target range of 40-80). Some have postulated that with an LDL that low, you will never get a heart attack or stroke. So, Niacin may indeed work, but not with super reductions of LDL's with statins.

One of the main points of from these findings is that we have to be careful when it comes to using surrogate endpoints (like LDL and HDL) for treatment. For example, lowering the LDL with a statin reduces heart attacks and strokes. However, lowering the LDL with ezetimibe (Zetia) doesn't seem to do this (see here for more details) This might be the case for Niacin and HDL as well.

I have never been a big fan of Niacin because it causes pretty bad flushing, increases uric acid/gout, and most importantly raises blood glucose. Most of my patients are diabetic/prediabetic, so raising their blood sugar is not something I am too fond of. The other drugs that can raise HDL and lower triglycerides are fibrates. Gemfibrozil has clearly demonstrated this in a large VA study (VA-HIT). The problem with gemfibrozil is that it can interact with statins, causing some serious side effects. Statins are the one med that clearly works in just about everyone with increased cardiac risk. Fenofibrate works the same way, but can be used safely with a statin. However, when they tried to demonstrate cardiovascular improvements with fenofibrate (FIELD study), the primary outcome was not statistically significant. One of the differences between VA-HIT and FIELD is that more patients were on statins in FIELD, since FIELD was a more recent study and regular use of statins had become standard of care. However, in the diabetic patients with low HDL and high triglycerides, the FIELD study did show that fenofibrate reduced heart attacks and strokes. The ACCORD lipid study (another large, randomized, NIH sponsored trial), attempted to prove benefit by adding fenofibrate to all diabetics on a statin, but failed. However, similar to FIELD, in those diabetics with low HDL and high triglycerides, fenofibrate added to a statin did reduce heart attacks and strokes. The consistency of these findings therefore have some merit.

Bottom Line: Statins remain the first choice for patients at increased cardiovascular risk and should be used at doses that meet individual LDL goals and/or lower LDL by 30-40%. After that, the rationale for treating low HDL/high trigs is now less clear. Before we see the actual data from the AIM-HIGH study, it would be premature to pull all patients off of Niacin. That being said, in my opinion, Niacin's days are likely numbered. Evidence for raising HDL and lowering triglycerides seems to be much stronger for fenofibrate, at least in diabetics, and fenofibrate does not seem to have the negative effects, specifically hyperglycemia, seen with Niacin.

Metformin is first, but what diabetes medicine is #2?

2011-05-29T07:53:00.000-07:00

Most experts seem to agree that for type 2 diabetes, metformin should be the first line therapy for most patients, but there is significant disagreement for which agent holds the #2 spot. Recently, the NY Times wrote a piece "For Those With Diabetes, Older Drugs Are Often Best." claiming that docs should stick with the older, cheaper drugs. This may be true for metformin, but likely not for sulfonylureas which cause hypoglycemia, weight gain and do not sustain glycemic control. This means the next agent will need to be a branded drug. DPP4's likely Januvia and Onglyza and TZD's like Actos are but possibilities, and each has advantages and disadvantages over the other. The DPP4's are the newest agents and therefore have the shortest track record. We don't know whether they can sustain glycemic control, but 2 year data looks promising. However, they are very clean with essentially no side effects. The TZD's have been the best studied, and really the only drugs that have shown sustained glycemic control. However, they have more side effects including edema, weight gain, a very small risk of non-vertebral fractures, a very small risk of heart failure in those at risk, and of course the FDA's concern about myocardial ischemia with Avandia (though not a concern with Actos per the FDA). Both classes also come in combination with metformin.

For a more complete discussion, see my Medscape blog post "Metformin is first, but what diabetes medicine should be your second choice?" (You will need to create a log in and password for Medscape in order to see this).

Time to Get Together on Reducing Health Care Costs

2011-05-15T06:55:00.000-07:00

As reported in the Wall Street Journal Reports Show Strain of Health Costs, two reports just came out showing that out of control health care spending are about the crush the entire system and our country along with it. The first report is from the Medicare Board of Trustees which stated that unless something radically changes, Medicare will go bankrupt in 2024. The second report regards what we pay for health care. Per the WSJ Health Blog:

"The latest Milliman Medical Index, which measures the total cost of health care for a typical family of four covered by a preferred provider plan (PPO), rose 7.3% to $19,393 in 2011. The per-employee cost more than doubled between 2002 and 2011. And the employee’s share of that cost now stands at 39.7%."

In other words, escalating health care costs are destroying business in America making an economic recovery almost impossible and the health safety net for our senior citizens (which working non-seniors currently pay for) will shortly disappear.

We can argue whether or not heath care in America should be entirely government run or completely private. We can argue whether health care is a right for our citizens or an entitlement we can't afford. However, reducing the escalating cost of health care should be something both sides can come together on.

An editorial in today's Washington Post looks to where President Obama and Mr. Ryan could possibly come together:

"The current debate has an ideological incoherence on both sides. Republicans endorse a premium support model for Medicare even as they work to undo the new insurance exchanges in the health-care law. Democrats distrust premium support when it comes to Medicare but support the exchanges, with sliding scale subsidies that amount to premium support, in the health-care plan. The problem of getting health-care costs under control is complicated enough without knee-jerk opposition being the default reaction to any proposal from the other side."

Given that the 2012 elections are not far away, it is unlikely that there will be any common ground seeking in the near future. However, our country can not wait much longer for politicians to put away their partisanship and come together on the one thing that both sides can and should agree on: we are spending too much money on health care and it is bankrupting the country.

May is National Women's Health Week

2011-05-09T13:08:00.000-07:00

Happy Mother's Day! Hopefully, you sent your mom flowers, cards, etc. (or at least gave a phone call). In thinking about mom (and all the women in our lives), it's important to remember their health. And, what better way to honor and celebrate the women in our lives than to support their health during National Women’s Health Week. Last week, the Kaiser Family Foundation issued a new report on Women’s Health and it’s clear that many women put their family obligations and friends ahead of their health. Here are five suggestions for women (or the women in your lives) to take control of their health:
5 Ways to Take Control of Your Health During May Women’s Health Week

1. There’s a Doctor in the House. This month, schedule an appointment with your health care professional to receive your regular checkups and preventive screenings. The new health care reform legislation requires new health plans to cover recommended preventive services, including mammograms, colonoscopies, immunizations, and well-baby and well-child screenings without charging deductibles, co-payments, or co-insurance. It also assures women the right to see an OB/GYN without having to obtain a referral first. To learn more about the new benefits and cost savings available, please visit http://www.healthcare.gov/.

2. Move! Exercise is critical to staying healthy and managing chronic diseases such as diabetes, hypertension and arthritis pain. And, exercise can help prevent more serious complications, such as diabetic peripheral neuropathy (DPN) in diabetics. With the responsibilities of work and family, it’s understandable that it might seem impossible to find the time and motivation to get moving. But physical activity can be as simple as taking the stairs, taking a walk at lunch with coworkers, setting a good example for your family by playing with your children outside, or going dancing with friends or family.

3. "Winning" by unwinding. Many women feel heavy stress from health, economic, and family issues, including health problems of their family members, financial concerns, and career challenges. Mental health is an often overlooked but critical aspect of women’s health care. Pay attention to your mental health, including getting enough sleep and managing stress to help prevent chronic disease. Take some “me time” to relax and meditate. Give yourself a pat on the back for taking steps to better health.

4. Food for Thought. An important factor in preventing chronic diseases is to maintain a healthy weight. Eating a balanced diet high in fruits and vegetables, whole grains, lean protein and dairy, and “good fat” is easier than think. Eating right for you also sets a good example for your family.

5. No Smoking! Avoid risky behaviors, such as smoking. Speak with your health care provider and your employer about benefits and resources available to help you quit like the one available to Federal Employees and retirees

Using Actos to Prevent Diabetes

2011-04-01T08:32:00.001-07:00

Recently, the New England Journal of Medicine published a study showing that Actos prevented the development of diabetes in patients at risk for developing diabetes (Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance). Though this has not generated significant mainstream media buzz, bloggers Matthew Herper from Forbes (Why You Don’t Want A Pill To Prevent Diabetes) and Amy Tenderich from Diabetes Mine (10 Reasons Why The Actos Pre-Diabetes Study is Dumb) strongly disagree. Since many patients follow these popular blogs (far more popular than mine), I thought it would be important to throw a clinician's point of view into the ring.

The NEJM study randomized over 600 patient who were at high risk for developing diabetes to pioglitazone (Actos) or placebo and found that after about 2.5 years, 2.1% in the pioglitazone group and 7.6% in the placebo group progressed to diabetes (which is a relative 72% risk reduction). On the down side, patients on pioglitazone gained about 7 pounds more and about 7% more had edema.

To assess the value of using TZD's like Actos to prevent diabetes, it is important to understand what diabetes really is, how it is defined, and why TZD's might be a very important option despite the associated risks. Unlike type 1 diabetes which is mostly about the destruction of the beta cells in the pancreas and subsequent lack of insulin, type 2 diabetes is a long process that is about much more than blood sugar. Type 2 diabetes is a result of genetic factors that control how individuals utilize glucose, about age, and about obesity. These factors combine to cause much more than just the body's impaired ability to utilize sugar. There is increased inflammation, worsening of cholesterol, increased blood pressure and increased blood clotting, just to name a few. All of these factors, including elevated sugar, combine over years and years to increase the risk of microvascular complications (eye, kidney, nerves) and macrovascular complications (heart attack and stroke). The process occurs for many years, and it is estimated that at the time of diagnosis of diabetes, the process (let's call it metabolic syndrome) has been going on for about a decade and that about half of the pancreas' function is lost despite having relatively high levels of insulin. Men who meet the diagnostic criteria for metabolic syndrome have three times the risk of heart attack and stroke and women who meet this criteria have six times the risk.

When we call a diabetic a diabetic is quite arbitrary. The guidelines used to classify diabetes as a fasting glucose of 140. This was lowered several years ago to 126 recognizing that complications were occurring at sugar levels lower than 140, and the cut off of 140 was too high because it was delaying treatment. More recently, in 2010 the ADA recommended that diabetes be diagnosed at a hemoglobin A1c of 6.5% or greater, recognizing a fasting glucose of 126 missed many of the diabetics with impaired post-prandial glucose, thus leading to possible delays in therapy. In fact, based on this new criteria, some of the patients in the Actos study who were not classified as having diabetes, would now be called diabetics. It is not inconceivable in the near future, that the threshold for diagnosis and treatment of diabetes occurs at an even lower fasting glucose number, A1c, or some constellation of markers. In other words, whether or not we are really preventing diabetes or just delaying the time to reach an arbitrary threshold is more of semantics. The bottom line is that in patients with impaired fasting glucose, there is an underlying disease process leading to complications that ought to be addressed.

To make an informed decision, one has to review the three main studies that looked at drugs for the "prevention" of diabetes. The study above for Actos, was very similar in design and findings to the other TZD rosiglitazone or Avandia called the DREAM study. The other major study, called the Diabetes Prevention Program (or DPP) looked at metformin vs. diet and exercise vs. placebo. Interestingly, diet and exercise beat metformin for preventing diabetes. Why would this be? It has to do with the fact that diet and exercise reverses the process of insulin resistance whereas metformin merely lowers blood sugar. Metformin was not included in the rosi or pioglitazone studies, nor was there a diet and exercise arm, so it is hard to compare all three interventions (diet/exercise, metformin, TZD) in preventing diabetes complared to placebo. However, troglitazone, an early TZD which was pulled from the market for liver complications (Actos and Avandia have not shown these problems) was initially used in the Diabetes Prevention Program (DPP), but was stopped after less than a year. Interestingly, in that short time, troglitazone did better than both metformin and diet and exercise. In other words, when you address insulin resistance and metabolic syndrome either by diet and exercise or with a TZD, you prevent diabetes much better than with a drug like metformin that only addresses blood sugar or placebo. This is important because the Actos study not only showed decreased rates of diabetes, but also showed statistically significant decreases in blood pressure, plaque build up, and increases in HDL or good cholesterol.

This begs the question, if you can prevent diabetes (or treat the underlying process that has not yet met the arbitrary criteria to be called diabetes) with Actos or lifestyle modications, why would you choose a drug? The answer is that lifestyle modifications is always preferred, but often not practical or easy to do. For the lifestyle intervention group in the DPP, participants were instructed to limit their calories to 1200-1800, get 150 minutes of exercise a week, had 16 sessions of counselling, and access to nutritionists, personal trainers, and behavioral counsellors. Another way to look at this is that anyone can go on "The Biggest Loser" and lose weight if they are given that amount of support (and time to take off from work), but this is not always practical. Interestingly, much of this support is not covered by traditional health insurance (where medication is), and once could argue that this is where we ought to devote our precious health care dollars (topic for another post).

As a physician, I need to help my patient the best way I can. I need to be practical. For all patients, diet and exercise is clearly the first step and always encouraged at every step. However, practically speaking, this just doesn't work all the time. It takes a highly motivated patient with a lot of resources and support to do this. Thus, if I can use a medication that will help reverse the underlying disease process of insulin resistance and delay the diagnosis of overt diabetes (along with diet and exercise), then I believe I am ethically obligated to do so.

Finally, the big issue that has been brought up is side effects. Mainly weight gain and heart failure. First, the TZD's do not "cause" heart failure. What I mean by this is that Actos has no direct effect on the heart. What is does do is increase fluid retention. For patients whose hearts are not working that great (pre-heart failure), a little extra fluid can push them into heart failure. Though this is a serious risk, it is not that common and can be addressed by carefully monitoring patients before and after treatment. Secondly, weight gain is a real issue. There are two components of weight gain caused by TZD's. The first is the aforementioned fluid retention. The second has to do with reversing the underlying disease process. Patients with diabetes and metabolic syndrome do not utilize glucose correctly. This causes subsequent increases in insulin and eventual pancreas failure leading to the need (over years) of supplemental insulin. By not using sugar, weight is not gained. By correcting the process, the sugar goes to where it is supposed to, which leads to weight gain. However, it is not clear that this weight gain is necessarily "bad." Studies show that TZD treated patients shift their fat from the dangerous visceral abdominal fat (associated with high cardiovascular risk) to more centralized fat stores. In other words, though not proven by a randomized control trial, reversing the disease process (glucose, cholesterol, blood pressure, weight gain) is likely to prevent more adverse events (heart attack and stroke) then events caused by additional weight.

Bottom line: Obesity is an epidemic in our country and will soon be the single leading cause of preventable death in the US. Along with obesity comes diabetes, which takes years to develop and is defined by arbitrary criteria. This diease process (metabolic syndrome) is associated with it's own consequences. Diet and exercise leading to subsequent weight loss and improved cardiovascular health is clearly the best choice. However, for most patients for very practical reasons, this method is not successful. Until there are changes to our health care system and/or public health initiatives that make intense lifestyle modifications more reasonable, pharmacotherapy to prevent diabetes has an important role. Pioglitazone has demonstrated that it can effectively prevent diabetes in most patients with known but manageable side effects, and therefore should be considered a useful tool.

Good Bye Primatene Mist

2011-03-18T11:10:00.000-07:00

As reported today by the Washington Post, Primatene Mist’s days are numbered. The FDA announced today that "the only over-the-counter asthma inhaler sold in the United States will no longer be available next year as part of an international agreement to stop the use of substances that damage the environment."

This is because, similar to the old albuterol meter dose inhalers, Primatene Mist uses a CFC as a propellant which is harmful to the environment. I blogged about this previously (see FDA Announces End for CFC-Propelled Inhalers Asthma inhalers and More on Asthma Inhalers ).

However, the loss of Primatene Mist is a good thing in my opinion. Primatene Mist is epinephrine. It is a bronchodilator, which is why it relieves the symptoms of asthma. However, it is quite dangerous, especially without a prescription. First, it is not just a beta 2 agonist like albuterol which works almost exclusively on beta receptors in the lungs. It also aftects beta 1 receptors in the heart and alpha receptors in the blood vessels. The primary use of epinephrine is medicine today is to give it to patients who are a risk of immediate death in order to restart their hearts. In addition, having any bronchodilator, even albuterol, over the counter, is a bad thing. We know that increased albuterol use is associated with increased ER visits, hospitalizations and even death. But at least we can monitor albuterol use, because it must be prescribed by a physician. We have no way of knowing if a patient is taking too much Primatene mist until they are dead.

Under a physician's supervision, with a proper asthma plan and additional chronic maintenance medications for asthma, such as inhaled corticosteroids, bronchodilators can be used safely and effectively. However, over-use of these medications especially in the absence of inhaled corticosteroids is dangerous. This is why I never write an albuterol prescription with any refills. If your asthma is well controlled, one albuterol inhaler should last you a year and you shouldn't need refills. If you are refilling the albuterol more than one time in a year, by the NIH's criteria, your asthma is not under control and you may need to change to a stronger daily medication (for example, switch from Singulair to an inhaled corticosteroid or ICS, or switch from an ICS to an ICS/LABA combination).

For those patients without prescription insurance who relied on the relatively low cost of OTC Primatene mist, be advised the GSK makes a sample size of Ventolin HFA (60 inhalations) that is only $9 out of pocket (regardless of insurance) at most major retail pharmacies. This will of course require a doctor's prescrition, but I believe that is a good thing for the reasons stated above.

2011 Residency Match NOT Good News for Primary Care

2011-03-17T17:54:00.001-07:00

The there are currently few reports of this in the mainstream press, the AMA news announced "Residency Match sees continued growth in primary care." The American College of Physicians reports on their web site states "Residency Match Results Encouraging for Adults Needing Primary Care." Kevin Pho of KevinMD appropriately wonders whether this increase is enough to save primary care in his post "Match Day 2011: Family medicine grows, but enough to save primary care?" based on the assumption that this year's match meant good news for primary care.

Don't believe the hype.

This was not a good match for primary care or our health care system in general. These positive reports are based on the press release from the National Resident Matching Program or NRMP which is the group that runs the match. They stated that

"The number of U.S. seniors matched to family medicine positions rose by 11 percent over 2010 . Among primary care specialties, family medicine programs continued to experience the strongest growth in the number of positions filled by U.S. seniors. In this year’s Match, U.S. seniors filled nearly half of the 2,708 family medicine residency slots. Family medicine also offered 100 more positions this year.

The two other primary care specialties that increased in popularity among U.S. seniors were pediatrics and internal medicine. U.S. seniors matched to 1,768 of the 2,482 pediatric positions offered, a 3 percent increase over 2010. In internal medicine, U.S. seniors filled 2, 940 of 5,121 positions, an 8 percent increase over last year."

At first glance, this seems like good news for primary care. However, their use of statistics is misleading. They are not taking into account that there were almost 500 more US medical students in the match this year. This is equivalent to a drug company telling you that their medication reduces hearts attacks by 30% (from 50 to 35), but forgets to tell you that there were 1000 patients in each group, so that the real reduction in heart attacks is only 1.5%.
What you need to look at is the percent of US medical students that matched into that speciality and whether or not it changed from last year to this year. If you go to the NRMP web site, you can get the actual raw numbers. For Pediatrics, though more US seniors matched into Pediatric residencies (remember there was about 500 more students this year than last), the percent of US seniors matching into Pediatrics was unchanged. For Family Medicine, there was a slight bump, but compared to last year, only about 1/2 of a percent more of US seniors chose to go into Family Medicine (far less impressive than the relative increase of 11%). The real big bump was in Internal Medicine, where almost 1% more US seniors matched into Internal Medicine. However, we know from previous studies, that only 2% of seniors that choose Internal Medicine plan to go into primary care. (See here for previous post).

What is also in the NRMP press release (that some are paying less attention to)

"Dermatology, orthopaedic surgery, otolaryngology, plastic surgery, radiation oncology, thoracic surgery, and vascular surgery were the most competitive fields for applicants. At least 90 percent of those positions were filled by U.S. medical school seniors.

The number of U.S. medical school seniors in emergency medicine increased by 7 percent and grew for the sixth year in a row, as they filled 1,268 of the 1,607 first-year positions available. Anesthesiology offered 44 more positions and matched 45 more U.S. seniors who filled 671 positions of the 841 offered "

Essentially, though there are more medical students this year than last, and thus more doctors available to society when they are done with their residencies, the same low numbers of students are choosing residencies that will lead to careers in primary care. This small increase will not make up for the many patients in the US who lack a primary care physicians and certainly won't even begin to fill the gap when many of our now close to 50 million uninsured patients suddenly gain insurance under health care reform. Rather, despite the clear need for more primary care physicians, our students continue to choose the more lucrative subspecialties.

America, this is a crisis. Many of the few primary care docs we have are retiring, leaving practice, or going cash only or retainer. Our students see this and continue to choose other specialties. If something is not done to increase the value, reimbursement, and job satisfaction of our primary care doctors; we will have no one left to care for our sick and aging population. (And before you post a comment about NP's and PA's filling this gap, those students aren't going into primary care either. A surgical PA makes more money than a primary care MD).

Using Twitter as an Audience Response System

2011-02-17T11:17:00.000-08:00

Readers of this blog will note that today's post is a departure from my normally medically related posts. However, I felt the need to use this space in the cloud to discuss an incredibly positive experience I had doing what I do when I don't see patients: teaching medical students.

In general, educators are often trying to find unique ways to engage their students. This is certainly true of medical educators, given that little has changed in medical education in the past 100 years, and for that reason there have been many recent efforts to change this. Similarly, there is often a generational gap between teacher and learner, and thus teachers look for ways to connect with the younger generation they are teaching. Social media and other web based technologies are thus a source of recent interest for medical educators. My colleague Dr. Katherine Chretien has been a pioneer in this field, using blogs to promote professional development in medical students and she has also looked at unprofessional behavior of medical students on social media outlets such as Facebook and physicians who use Twitter. There is even a website now dedicated to Social Media in Medical Education.

One technology that has been useful during classroom presentations has been audience response system or ARS. Most ARS systems work by giving students keypads, and at certain points in the lecture, students can key in their responses (usually anonymously) to questions posed by the lecturer. Use of ARS in lectures has many benefits. It allows learners to be more active and it allows the lecturer to gauge students' knowledge and whether or not they are teaching effectively. Also, because responses are generally anonymous, it can sometimes assist in discussing topics that are difficult to discuss openly. In one class I teach, we use an audience response system and trigger videos to discuss cultural competency and the difficult topic of one's own personal bias. Our medical school uses the Turning Point system for ARS, but only our first and second year students have the keypads (they return them before 3rd year), and I teach several 3rd year classes.

Thus, I was very excited when I found a SAP Business Objects Power Point Twitter Tools . This is a completely free download that allows you to integrate Twitter with a live Power Point presentation. There are several tools, but I was most interested in the ability to use Twitter as an ARS. Essentially, the students' web enabled smart phone becomes the "clicker" and they tweet their responses during lecture which the program magically displays on your Power Point slide. In addition, because students are using text and not just numbers on a key pad, you can also collect even more valuable information as live Twitter feeds. Today, I piloted this in an asthma lecture. In addition to the typical knowledge based multiple choice ARS questions I integrated with my lecture, to generate discussion, I also asked them which asthma medications their physician preceptors were most commonly using. By using a preset hashtag (I used #asthmamed) in their tweets, all their responses could be captured on the screen.

Several observations/pitfalls
1. Medical students do not use Twitter. Almost all have smartphones, and many are using Facebook, but very few use Twitter. I was only able to get about a half dozen students to pilot this because they did not have Twitter accounts that they had successfully used on their mobile phones (however, I only gave them 48 hours notice about the activity). Others may wish to comment on this, but based on my brief discussion today, our 3rd year medical students did not see the importance/relevance of Twitter. They found Facebook much easier for social connections, and didn't see the "need to follow Lady Gaga."
2. Delay time. Some of this might have been to student and teacher lack of familiarity with the system, but it is definitely not as fast as the traditional ARS systems. That said, it is probably fast enough.
3. Students can change their answers. This was an interesting occurrence that I hadn't thought of. Typical ARS systems make you commit then "lock you in." This is not necessarily a disadvantage, because you might want to look at changes, but something to consider.
4. Text responses are non-anonymous. When I asked students to tell me what asthma medications their preceptors were using, I could see who wrote what. Hopefully there is a way in the system to see the Tweet without revealing the "tweeter."
5. Technical issues. I was not able to save settings, and had to reset everything before the presentation. I am probably doing something wrong, but it took a lot of playing around on my part to get it to work the way I wanted.

If you are a medical educator and decide to try this, please email me or respond to this blog post with tips, suggestions or questions.

Similarities between porn and junk food

2011-01-29T06:51:00.000-08:00

The Angry Nutritionist is both informative and entertaining (and is very angry). His latest video on the similarities between pornography and junk food is worth a watch. He is particularly upset because there is recent evidence that despite public health education touting the benefits of fruit and vegetables, Americans are actually eating less. A study released this fall from the CDC showed that only 26 percent of the nation’s adults eat vegetables three or more times a day.

His points and videos are thought provoking. I would argue that cost is probably and instant gratification are probably the two things that are most similar. Because of the Internet, porn is now free. One could argue that the best way to get Americans to eat healthier is to make junk food more expensive and fruits and vegetables more affordable.

Cigarette Taxes Apparently Work

2011-01-04T05:12:00.000-08:00

Not to be negative about public health educational campaigns, which I believe are important, but the two major factors that have led to the decline in US smokers over the past decade are most attributable two two things: smoking bans and taxes on cigarettes. When it becomes difficult to smoke in public places and expensive do to so anywhere, people are more motivated to quit.
An article in the NY Times today caught my attention: In Japan, Pfizer Is Short of Drug to Help Smokers. The focus of the article regards how Pfizer was a little unprepared for the excessive demand of the smoking cessation drug Chantix (called Champix in Japan and elsewhere) when the Japanese government imposed a cigarette tax.

Being in the business section, the focus is on sales and Pfizer's handling of the situation. However, I am much more interested in the impact of the Japanese cigarette tax on behavior. Japan has a much high smoking rate than in the US. In 2009, about 40% of Japanese men smoked, compared to about 24% of US males. The Japanese tax started in October of this year. Prior to this, the rate of smokers in Japan decreased by about 2%. The tax increased the cost of a pack of cigarettes from about $3.60 US dollars to $4.80. Prior to the tax, ad campaigns sponsored by Pfizer, led to sales of Chantix to 70,000 patients a month in August, which more than doubled to 170,000 patients in September (just before the tax) and continued to grow in October (the NY times article talks about how Pfizer had to suspend prescriptions to new patients because they couldn't make enough Chantix fast enough to keep pace with demand).

The bottom line is that cigarette taxes have been effective in the US, and seem to quite effective in Japan based on excess demand for Chantix and a significant drop in Japanese smokers prior to the tax. With our economy still not in the best shape, health care costs escalating, and respiratory illness now rising to the 3rd leading cause of death in the US, we should consider increasing cigarette taxes even more.

Conservatives Should Read Ezra Klein

2010-12-14T07:40:00.000-08:00

I try not to get too polictical on my blog. I consider myself a moderate. I supported passage of the health care reform bill, but mainly because if it had failed, in my opinion, discussions of true health care reform would be stalled for another decade. Though there are some good things about the current legislation (removal of pre-existing conditions for example), there is nothing really that addresses the escalating costs of health care.

Though most political news recently has been about taxes, health care reform is in the news again today, due to a judge's ruling regarding the consitutionality of the individual mandate. You can read the NY Times or Washington Post's coverage. Pundits on the left and right will likely once again discuss their positions on both sides of the health care debate.

However, journalist (and notably liberal talking head) Ezra Klein had some very interesting comments that those on the right would be wise to take note of. In addition to pointing out that the President Obama was the one opposed to the individual mandate during the primaries and criticized Hillary Clinton for supporting this, he states:

The individual mandate began life as a Republican idea. Its earliest appearances in legislation were in the Republican alternatives to the Clinton health-care bill, where it was co-sponsored by such GOP stalwarts as Bob Dole, Orrin G. Hatch and Charles E. Grassley. Later on, it was the centerpiece of then-Gov. Mitt Romney's health-reform plan in Massachusetts.....It was only when the individual mandate appeared in President Obama's legislation that it became so polarizing on the right..... The individual mandate was created by conservatives who realized that it was the only way to get universal coverage into the private market. Otherwise, insurers turn away the sick, public anger rises, and, eventually, you get some kind of government-run, single-payer system, much as they did in Europe, and much as we have with Medicare. If Republicans succeed in taking it off the table, they may sign the death warrant for private insurers in America: Eventually, rising cost pressures will force more aggressive reforms than even Obama has proposed, and if conservative judges have made the private market unfixable by removing the most effective way to deal with adverse selection problems, the only alternative will be the very constitutional, but decidedly non-conservative, single-payer path.

In other words, the only way that we can afford health care coverage for most Americans (whether it be provided by the government or the private sector) is if everyone pays something to have it, and the fiscally conservative Republicans knew this, which is why they suggested this in the first place. Interesting.

Don't Call Me for A Prescription for Your Aspirin

2010-11-11T18:16:00.001-08:00

As reported by MSNBC, the federal government will no longer allow flexible spending accounts (FSA's) to be used for over the counter medications, without a prescription. FSA's, which are offered by many employers, allow you to use tax free dollars for medical expenses that aren't covered by your insurance. FSA's are a great idea and can be used for things like eye glasses, dentistry, or even nicotine patches for smoking cessation.

The people most likely affected by this rule are those that take over the counter medications on a regular basis. Examples of such medications include pills for allergies, heartburn , aspirin for heart attack prevention, and smoking cessation aids. Medical supplies like insulin syringes and crutches, though sold over the counter, are exempted.

Now, you might think, "no big deal, I will just call my doctor and ask her to call in a prescription for a baby aspirin a day." This would certainly solve your problem, but it adds to your physician's problem and is a perfect example of the problems with the reimbursement system for health care, particularly for primary care.

If you are not aware by now, procedures get reimbursed much more than just talking to patients, which is why cardiologists make so much more than primary care physicians. However, anything that doesn't happen in an office visit is generally not reimbursed at all. Primary care physicians can be great managers of your health care, done in a way that it convenient for you, and at a low cost- phone calls, emails, forms, etc. Problem is that the few minutes spent on you add up and take a whole lot of time. None of which is reimbursed by health care insurances under the current system. One doctor started adding these things up, and of the 50-60 hours each week the doctor put in, each day they:

Handled 23.7 phone calls.
Answered 16.8 e-mails, mostly dealing with test result interpretations.
Dealt with 19.5 lab reports, 11.1 imaging reports and 13.9 consult reports.
Issued 12.1 prescription refills, excluding those issued during patient visits

None of these are reimbursed.

Now, here's the real kicker about asking your doctor for an aspirin prescription. Not only are you compounding this problem, but you are also doing it not for better care (or any care for that matter), but so you can save money!
Finally, consider this:
Even though you can easily go to CVS and get aspirin on your own, if your doctor writes you a prescription for aspirin, legally speaking it is a whole different ball of wax. By writing a prescription, even if only for an aspirin, your doctor is rendering medical care. He is required by law to accurately document this. He is also liable for this care. If you had an adverse reaction to the aspirin prescribed, you could certainly sue.
Thus, by asking for a prescription for an aspirin, you are asking for the doctor to deliver care which he is liable for, which he will not get paid for, which (when added up for each patient) will take time away from true patient care and for the sole purpose of you saving yourself a few bucks.

Now, one of the reasons that primary care physicians have gotten into the mess that we are in is because we generally want to do what's best for the patient and have been delivering this kind of free care for a long time. We actually were glad to do it, and only started complaining recently when what we got paid for actual care kept declining while our specialist colleagues kept getting more money, and our paper work started to increase. Many of us (probably including myself) will likely grant these requests without a complaint.

The point of this post was not to prevent your from requesting an OTC prescription from your physician for tax purposes. After all, the economy is still horrible and many patients truly need daily medications for allergies and heartburn that are quite expensive. The point is that are entire health care reimbursement system must change, and must change very soon. A few requests for OTC prescriptions for FSA's on top of a 23% Medicare cut might be all it takes for a primary care physician to stop practicing medicine altogether.

Spiriva for Asthma?? Not so fast.

2010-09-20T05:54:00.000-07:00

There is a lot of press about a study just published in the New England Journal of Medicine that shows that adding tiotropium (Spiriva) to an inhaled steroid might have benefit in asthmatic patients. This study is creating a lot of buzz due to recent concerns of ICS/LABA safety and might prompt doctors and patients to start switching (some already have before this study came out). However, this would be a HUGE mistake.

The study was a small study of 210 patients that compared the addition of tiotropium (Spiriva) which is a a long-acting anticholinergic inhaler currently only used in the treatment of chronic obstructive pulmonary disease (COPD) to an inhaled corticosteroid (ICS), and compared this to
doubling of the dose of the ICS or adding the long-acting beta agonist (LABA) salmeterol.

The primary endpoint of the study was improvement in morning peak flow, which they found that adding tiotropium increased by 25.8 liters per minute (P<0.001) as compared to doubling the dose of the ICS. There was also improvement in secondary outcomes such as lung function as measured by FEV1, which showed an improvement of 0.10 liters (P = 0.004). In addition, when comparing additng tiotropium or salmeterol to ICS (the study was designed to show tiotropium was no worse), they found tiotropium slighlty better than salmeterol in terms of morning peak flow (6.4 liters per minute (P<0.001)) and not significanlty different in lung function (FEV1 difference of 0.11 liters).

With some safety concerns regarding the use of LABA's, (I have blogged about this before and the bottom line is that if taking with an ICS, there seems to be no problems with LABA's) the New England Journal article might tempt doctors to use tiotropium instead of a LABA in asthmatic patients, if the evidence suggests that the benefit is similar between Spiriva and Salmeterol. However, making this leap would be dangerous for several reasons.

1. Almost all the data supports the use of LABAs. This is an intriguing but small study. Clearly more studies are warranted. However, the question of adding LABA's vs doubling the ICS dose has been extensively well studied. The best source is the unbiased Cohrane Review. Their review included 48 studies (15,155 participants including 1155 children and 14,000 adults). In looking at the morning PEF (the New England Journal article's main end point), the Cochrane group found that adding LABA to an ICS (compared to doubling the ICS dose) showed a 16.30 L/min improvement from baseline. This is similar to what was found in the New England Journal study. In looking at FEV1, the Cochrance group found an improvement of 0.08 (CI 0.03 to 0.13), which is closer to what was found with Spriva and much higher than what was seen in the New England Journal study. In other words, in looking at 48 studies with thousands of patients, ICS + LABA performs a little better than it did in the New England Journal study, although it does not clearly beat the numbers of tiotropium.

2. There is no data on outcomes such as exacerbations. A small bump in peak flow or lung function is meaningless if patients are still getting sick. The main goal of asthma treatment is to prevent exacerbations. The New England Journal study was too small to show this. However, the Cochrane review clearly shows that adding a LABA to and ICS, compared to doubling the dose of the ICS clearly prevents exacerbations. They showed a statistically significantly lower risk of exacerbations requiring systemic corticosteroids in patients treated with LABA and ICS (RR 0.88, 95% CI 0.78 to 0.98, 27 studies, N = 10,578) from 11.45% to 10%, with a number needed to treat of 73.

3. There is no ICS/tiotropium combination inhaler (yet). One of the advantages to ICS/LABA combination inhalers is that both medications come in a single inhaler. This is critical. As mentioned, the LABA safety issues seems to occur when patients take LABA's without an ICS. This makes sense because even though the bronchodilator might make patients feel better, not treating the disease (inflammation) can lead to serious problems down the line. Because of this, the FDA recently recommned that children who take ICS and LABA's together only take them in the same inhaler. The worrry is that if the two inhalers are used separately, patients are at risk of only taking the brochodilator. Because the bronchodilator makes patients feel better, they are more likely to be adherenct to this inhaler than an ICS, which has effects that patients don't immediately notice. This same concern would be true of tiotropium, which is also a bronchodilator. However, ICS/anticholergic combination inhalers should be available soon. Studies will be now needed not only in COPD, but also in asthma to see which regimen produces the best benefit.

Bottom Line: This is an exciting study. By showing tiotropium has potential benefit in asthmatic patients, it may give clinicians and patients an additional tool to treat this disease. The study shows that use of tiotropium in asthma clearly warrants more research. However, doctors and patients should not start taking ICS and tiotropium over ICS/LABA, since the data (especially regarding exacerbations) is just not there.

Study 175 and the Need for Comparative Effectiveness Research

2010-07-16T18:27:00.000-07:00

Though I am not going to say that the New York Times lied, they either purposely and grossly misrepresented the truth or did a horrible job of reporting. In their article "Diabetes Drug Maker Hid Test Data, Files Indicate" the Times states that Avandia maker GSK "secretly began” a study which ”provided clear signs that it (Avandia) was riskier to the heart.” In fact, the study in question, called study 175, was a small, short study, that had no cardiovascular outcomes (only lipid data) and was not a comparison of Actos and Avandia. In fact, there were no patients taking Avandia in this study! In addition, from pages and pages of documents, the Times took an out of context comment about the study (a GSK memo which read that study 175 shouldn't see the “light of day”) to make their charges sound even more damning. The New York Times should be above this kind of sensationalist journalism.

Let me give you a breakdown of study 175, why it was done, what it showed, and most importantly how this relates to the need for comparative effectiveness. You can read the official GSK statement about study 175 here, or look at the data yourself, which comes from a letter to the FDA from Senator Grassley (via Pharmalot).

Both Avandia (GSK) and its competitor Actos (Takeda) came out around the same time in the late 90's. Both were insulin sensitizers or TZD's, a new class of drugs for diabetes; a disease which hadn't seen any new drugs in a while. Not surprisingly, the two companies with their respective products were pretty competitive. The Takeda drug reps were usually quick to point out that though both products improved diabetes control, Actos did a better job on lipids. (Note that in addition to improving diabetes, the TZD's have a positive effect on lipids). The Actos people were able to make this claim because in their studies, Actos lowered triglycerides or fats by about 9% and in the GSK studies, Avandia didn't have much of an effect on triglycerides. This is a common tactic used by drug reps and breaks a cardinal rule of evidence based medicine: you can not compare products across studies, because in each study the populations and circumstances might be different. The only real way to make a comparison is in a head to head comparative trial. (This point remains very relevant, because the recent FDA advisory committee somehow concluded that Actos was safer than Avandia without one head to head trial!)

However, GSK noted an additional flaw in the Takeda claims. In the Actos studies, the patients started out with an average triglyceride level of about 260 mg/dL, where the patients in the Avandia studies had baseline triglyceride levels closer to 180mg/dL. In other words, if you start with worse numbers, you are more likely to show a bigger improvement. How well would Actos do on triglycerides in patients with closer to normal levels of triglycerides (normal is less than 150mg/dL)? One way to find out would be to do a head to head study comparing Actos to Avandia in patients with similar cholesterol and triglyceride levels. GSK could have certainly done this, but what would happen if the GSK study proved that Actos did indeed work better on triglycerides? Before spending a substantial amount of time and money on a study that could ultimately hurt the company, GSK did study 175 which looked at lipid levels in patients taking Actos who started with relatively normal cholesterol levels. Though they compared this to historical Avandia data, this was not a true head to head comparison, but likely enough information to tell them whether or not to proceed with the head to head.

I have pasted the main results from study 175 below (though you are welcome to go through the entire 158 Grassley letter). What you can see is that the higher dose of Actos dropped triglycerides about 16 points (or about 10%) and Avandia at the higher dose raised triglycerides by about 11 points. Study 175 also showed that Avandia raised the LDL or bad cholesterol by about 10%, where Actos didn't have any change (advantage Actos) and that Avandia raised HDL or good cholesterol by about 4 points (roughly 10%), whereas Actos didn't really raise the HDL (advantage Avandia). Given that these results might put Avandia at a competitive disadvantage, GSK decided not to publish their findings and did not to go forward with the head to head study. Thus, the company did not secretly hide data that Avandia was dangerous (as Grassely and the Times suggest). Rather, GSK chose to not to publish an Actos study that didn't make Avandia look any better.

Now you might argue (am I am guessing that this is Grassley's point) that since Actos did better with triglycerides and LDL cholesterol than Avandia, that this shows Avandia might pose a cardiac risk. In fact, many have argued this as the very reason that Avandia seems to show safety signals in meta-analyses and Actos doesn't. However, time and time again, surrogate markers have shown us that they don't translated into outcomes. First, all diabetics should be on statins, so these minimal changes in lipids seen by both TZD's probably don't matter clinically. Second, both the FIELD trial and the recently published lipid arm of the ACCORD study showed that even if you treat diabetic patients with medicines that truly lower triglycerides (fenofibrate), it doesn't reduce heart attacks. Furthermore, though there are only a few studies in diabetics showing raising the HDL decreases heart attacks, even Dr. Steve Nissen in his PERISCOPE trial that showed Actos to reduce plaque build up compared to the older sulfonylurea drug, suggests this may have been due to the HDL effect. In other words, if HDL is more important in preventing heart attacks in diabetics than triglycerides, maybe Avandia is the real winner of study 175. Though I am not going to suggest (similar to the Times and Grassley) that study 175 showed Actos to be more dangerous to the heart due to Avandia's HDL benefit, it is clear that study 175 does not show in any way, shape or form, that Avandia is more dangerous than Actos.

However, if you still feel the public has a right to know all the data (which is a valid point), GSK didn't just "hide" the data; they had an obligation NOT to publish it. GSK (and every drug company) is a for profit business. Though they have an obligation to patients to make safe and effective products, they also have a fiduciary obligation to their shareholders to make money. Similarly, though Toyota has an obligation to warn the public about any safety issue with its cars, it can not publicly declare that their Sienna minivan has fewer cup holders than Honda's Odyssey mini-van. Nor should Starbuck's need to announce that in a blinded taste test, most people preferred the cheaper McDonald's coffee. In all three cases, share holders could sue the company.

The main problem is that the majority of pharmaceutical studies are done by the pharmaceutical companies. The purpose of these studies are to get their drug approved for initially for availability on the market and eventually use in other indications. In 2005, pharma spent nearly $40 billion in research. This dwarfed the entire NIH budget that year of $28 billion dollars, and the NIH does very little research on drug therapies. You can't have your cake and eat it to. If you want unbiased studies, and if you want science and not marketing to determine what studies get done, then someone besides the industry is going to have to do the work.

Indeed, it is rare that industry published head to head studies. In some cases, such as Merk's ENHANCE study which showed its expensive product Vytorin to be no better a reducing plaque buildup thant its recently generic simvastatin, the company lost big time. Use of Vytorin decreased dramatically, and Merk's stock plummeted. In fact, the TIDE study comparing Actos to Avandia (which the FDA advisory committee approved to go foward with 19 to 10), only got started in the first place because the FDA mandated that GSK do this study. Ironically, in this Avandia "win" from this past week, GSK is footing the bill for TIDE, spending millions while sales of Avandia will likely plummet. If we had comparative effectiveness research in place back in the 90's the TIDE study would likely have already been completed and we would know with 100% certainty whether there was any TZD risk for heart attacks and any difference between Actos and Avandia.

This is why comparative effectiveness research is so important, and why it is a much needed improvement that came out of the recently passed health care reform bill. The health care reform act included about $500 million for a Patient-Centered Outcomes Research Institute
to do comparative effectiveness research. The funding builds on about a $1 billion dedicated to comparative effective research from the stimulus package. However, though an important start, $1.5 billion over the next decade is a drop in the bucket compared to the funding needed to answer important clinical questions about which medications are best in which patients. One possibility would be to have industry and government partner in such a way that the industry kicked in with only limited input into the research, which would also absolve them from their fiduciary responsibility to their shareholders. Other agreements could include more data transparency and independent analysis of drug company sponsored studies before publication.

The recent Avandia hearing with its media sensationalism from the Times and politicking by folks like Grassley and insiders within the FDA shows that when science, politics and media mix; patients lose. Not only is more transparency needed in both the FDA and the industry, but we have not been wise to allow industry to foot the bill for most of our research on therapeutics. Comparative effectiveness research provided in the health care reform bill is a start, but is grossly underfunded for what is really needed.

One Patient Stays on Avandia, One Patient Switches to Actos

2010-07-15T12:42:00.001-07:00

The calls/emails have already started to come in, and I expect more, as I have a lot of diabetes patients and have been an avid user of the TZD class. There are many reasons to like the TZD's:
1. The older, generic medicines like metformin and sulfonylureas are known to fail over time. After 3 years, most patients on one of these drugs lose control of their blood sugar. In contrast, patients on TZD's maintain glycemic control (at least up to 4-5 years which was shown in the ADOPT study).
2. The TZD's don't cause hypoglycemia, which is a really bad side effect of insulin and the sulfonylureas.
3. Many diabetic patients need more than one drug, so even if you start with metformin, you are going to have to choose between a TZD (well studied, no hypoglycemia), a sulfonylurea (well studied, causes hypoglycemia), or a DDP4 inbitor like Januvia/Ongyza (not as well studied, no hypoglycemia).
4. TZD's have other benefits that the other diabetes drugs don't, such as improving good cholesterol or HDL, and decreasing triglycerides or fats. In his presentation the Periscope study, which showed Actos prevented plaque build up, Dr. Nissen (wonder why he likes Actos?) compared these results to other similar cholesterol lowering studies and showed an ldl-independent effect of the TZD's in their ability to prevent plaque build up. He believed this was due primarily to increases in HDL.
5. Using a TZD, likely because of sustained glycemic control, prevents the need for insulin. This was shown in the recently maligned RECORD study and the NIH sponsored BARI-2D study. Insulin causes hypoglycemia and most of my patients would like to avoid insulin.

The first patient contacted me by email related what he had heard about the FDA panels finding. He understood that they recommended not to pull the drug, but also felt that there were enough concerns that he wanted to switch. He was on Avandia 4mg, so I switched him to Actos 45mg.

It is important to note that the TZD's have their maximal effect at the maximum dose. Though the maximum dose causes the most side effects, I have found that if used early in the course of disease, side effects are minimal. The most common side effect of the TZD's is edema, or fluid retention. Use of a low dose fluid pill (which many diabetics use anyway in order to keep their blood pressure controlled) seems to eliminate this problem. For metformin, the best dose is 2000mg a day (usually 1000mg twice a day).

This brings me to the second patient who called me with similar concerns. He had been taking Avandamet 4/1000mg twice a day for about 7 - 8 years with outstanding diabetes control. In discussing the switch to Actos, we uncovered a problem. The equivalent dose of Actos is 45mg. Like Avandia, Actos comes in combination with metformin, called Actoplusmet. Actoplusmet comes in 15/500mg and 15/850 and is to be taken twice a day. If you do the math, it is very hard to get the 45/2000mg a day that would be equivalent to the Avandamet dose that has kept this patient under control for so long. We could do two pills in the morning and one a night (a more complicated regimen), but would be over (more side effects) or under (less efficacy) on the metformin dose between the 850 and 500 versions. Actoplusmet was just approved as an extended release product. This can be taken once a day (easier regimen). Actoplusmet XR comes in 15/1000 and 30/1000. If we went this route we could have the patient take one of each. The problem is that his insurance company will consider this two different medications and charge him two separate co-pays. He could take the 30/1000 and use one and a half tablets a day (wouldn't cost him more), but we would be short on the metformin, and it is generally not a good idea to split extended release pills. After spending 10 minutes discussing the above dilemma, he decided that it was simply too complicated to switch and he would stick with the Avandamet, unless the FDA decided to pull it.

Actos and Avandia are both good medications. Many of the FDA panelists who voted to pull Avandia or severely restrict it, mentioned that they did so because Actos was available and they saw no clear avantage of Avandia over Actos. No one mentioned the dosing. This is likely because few on the panel actually treat patients with diabetes. The only panelist really pushing for options was the patient advocate.

In addition, there is really no compelling evidence to believe that Actos is any safer than Avandia. The AHRQ (government, non-pharma) commissioned a study to look at this, and they found no difference. A Science Advisory From the American Heart Association and American College of Cardiology Foundation also looked at this issue (most of the authors had no ties to either product) and similarly found no substantial difference between Actos and Avandia with regards to safety. This is also why the panel voted 19-10 to move forward with the TIDE study.

Though, I am sure I will continue to get emails and phone calls from worried patients, many of the patients I have on Avandia take Avandamet 4/1000mg twice a day. Hopefully, they will read my blog before calling as multiple 10 minute phone calls start to add up.

FDA Panel Recommends Keeping Avandia on the Market

2010-07-14T13:33:00.000-07:00

As I mentioned in my post Avandia Smackdown!! , I suspected that Avandia would likely stay on the market. The story is all over the headlines, including the Wall Street Journal's FDA Panel Backs Keeping Avandia on the Market. The 12 panel members wanted to pull Avandia, but 20 said it should stay on the market. More interestingly, though the majority of the members felt there were signals of risk, the vote was 20 to 10 to proceed with the controversial TIDE trial, which Drs. Graham and Sen. Grassley said were unethical.

I have been following the hearing closely for the past few days via Twitter and live video feeds from CNN. Here are some initial thoughts.

1. Despite the panel's concerns about Avandia safety, the clear majority felt that there was simply not enough data. Many were concerned that studies like Nissen's meta-analysis were just not strong enough. Though they favored long term, randomized trials to definitely answer these questions, unfortunately, there were enough concerns about the RECORD study by some (low events, withdrawals, and some missing data) to be convincingly reassured.
2. The sentiment of many was because Actos didn't show as strong signals, it remained a better option. Many who chose to pull Avandia stated for the RECORD that Actos' availability was a deciding factor. This is concerning because the data for Actos safety is extremely weak (not that I think Actos is dangerous). One panelist stated what I have heard before, that "the absence of evidence does not equal the evidence of absence."
3. Many panelist stated that they were putting on their "public health" hats, meaning that even though scientifically they were not convinced of real harm, because there was a possibility of harm, they voted to remove or proceed with caution. This is VERY important, because as a clinician (which many on the panel were not), you have to balance risk and benefit every day. Is the side effects of a particular medicine worth the benefits of the medicine? Is the potential harm of radiation worth the need for a CT scan? I think if more practicing doctors were on the panel, fewer would have voted to remove the drug.

What now?
Ultimately, the FDA will decide what to do. Since the FDA doesn't have to agree with the panel and especially since the panel seemed split, the FDA could decide to remove Avandia anyway or keep on the market with certain restrictions. Given that 10 voted to have very strict warnings, it is likely that's what the FDA will do. These stricter warnings will likely include something like requiring only a diabetes specialist, i.e. an endocrinologist be able to write a prescription for Avandia. This language will be crucial, because even if Avandia stays on the market, if the restrictions are tough enough, no doctor will ever write for the prescriptions.

Despite all the holes that Avandia's opponents poked in the data, I remained convinved that the preponderance of the data points in Avandia's favor. It doesn't appear to cause increased heart attacks, it certainly doesn't cause increased death, seems to decrease stroke, and clearly decreases the use of insulin. I will continue to write for the product unless it is pulled from the market, newer restrictions make it virtually impossible to prescribe, or my patients request being placed on a different medicine.

Avandia Smackdown!!

2010-07-04T06:26:00.000-07:00

This is it. The final countdown.
The fate of Avandia will likely be decided in a matter of days.
The outcome will likely have long lasting impact regarding how the FDA manages potential safety issues with any current or future drugs on the market.
That is because on July 13th and July 14th, the FDA will hold an advisory committee to review the safety data on GSK's drug Avandia.
I have blogged on the Avandia topic extensively. (In particular see Avandia Vindicated and Diabetes Conspiracy).
Below is a re-cap of all the major events in the saga as well as possible outcomes and my prediction as to what will happen.

Prelude- Vioxx (2001 -2004)
It is important to note that the Avandia story begins with Vioxx. Prior to Vioxx, many doctors prescribed heavily marketed drugs with less concerns about safety, thinking that if a drug had been approved by the FDA, they were likely safe. One of the major studies that led to fall of Vioxx was published in JAMA on August 22nd, 2001 by Cleveland Clinic cardiologist Dr. Steve Nissen. It took nearly three years until September 30th, 2oo4, when Vioxx was finally pulled from the market. Dr. David Graham, an FDA insider who works on drug safety was clearly frustrated by the FDA's apparent lack of concern. He was called to congress in November of 2004 to testify regarding what other drugs the public might be concerned about. Though Avandia wasn't named as one of Dr. Graham's five drugs to look out for, his testimony to congress against his own institution made it clear that Graham intended to be a whistle blower and would place the FDA safety folks at odds with the other branches of the agency

August, 2006- FDA becomes aware of potential Avandia issue
In August of 2006, GSK submitted both a pooled analysis (meta-analysis) of 42 separate double-blinded, randomized, controlled clinical trials to assess the efficacy of rosiglitazone (Avandia) for treatment of type 2 diabetes, which surprisingly showed a potential increase in myocardial ischemia in patients taking Avandia compared to placebo. There were no problems when Avandia was compared to other diabetes meds, no issues with death, heart attack, or other adverse events in the FDA's meta-analysis. These results were surprising because though Avandia was known to cause fluid retention and a possible risk of congestive heart failure (CHF), due to some of Avandia's other properties (lowering triglycerides, increasing HDL, decreasing CRP), if anything, Avandia should have prevented heart attacks.

Rather than create a public hysteria and mass panic, the FDA decided to take a wait and see approach for several reasons. First, the FDA knew that two large, randomized trials (ADOPT and DREAM) were about to be published that could help shed some light on this surprising and potential safety signal. In addition, the RECORD study was a large, randomized trial designed specifically to answer the question of cardiovascular safety and Avandia. Though the results would not be available until 2009, the study had be going on for almost 2 years and an independent group which periodically looks at the study to assess safety (commonly done in safety studies) had not reported any problems. And in fact, both DREAM trial and the ADOPT trial not only showed that Avandia prevented diabetes and sustained glycemic control better than the other available diabetes agents respectively, there were NO signs of heart attack.

Thus, the FDA felt confident in their decision not to needlessly scare the public, but rather wait until about June, 2009 when the RECORD trial was likely to report out. Given that it was a large, randomized trial specifically designed to look at Avandia and cardiovascular safety, the RECORD study would be able to definitely answer the question once and for all.

May 2007- Nissen Meta-Analysis published.
Due to a previous settlement regarding their drug Paxil by then attorney general Elliot Spitzer, all GSK's clinical trial data was publicly available. Dr. Steve Nissen was therefore able to perform his own meta-analysis of the GSK studies. Given that there had been no public mention of Avandia heart attack concerns, I suspect someone inside the FDA tipped off Dr. Nissen. His controversial and often criticized findings of a 43% increase in heart attacks with Avandia were rushed to press and published in the New England Journal of Medicine. The news created a media frenzy. Congressional hearings were called for by Senator Charles Grassley the very next day (almost as if Sen. Grassley knew about the results before they were published). In the following week's issue of the New England Journal, the interim results of RECORD were published ahead of schedule, mainly due to concerns that the RECORD study itself could be jeopardized as patients might pull out of the study if Avandia were dangerous. Though only more than half way done, the study seemed to show no signs of heart attacks, thus refuting the Nissen publication. However, the study was accompanied by not one, but three editorials discrediting the study, and the controversy persisted.

July 2007- First FDA Advisory Committee Convened
Given the publicity of the Nissen study, the FDA met to discuss the safety of rosiglitazone. After review of all of the FDA's (not Nissen's) data, they saw something that didn't make sense. Their own meta-analysis showed a signal of myocardial ischemia, but analysis of the ADOPT, DREAM and RECORD trials, as well as analysis of large claims databases showed nothing. The FDA voted almost unanimously to keep Avandia on the market. However, they added a boxed warning to Avandia. This boxed warning remains one of the most confusing warnings I have ever seen, stating that there is contradictory evidence so no conclusion can be made. Nevertheless, physicians who may have been on the fence about prescribing the drug, likely stopped writing prescriptions for Avandia. The class of medications, called the TZD's, decreased in general use, and Actos, the competing TZD which had 50% of the market share of TZD prescriptions became the heavily favored product.

June 2009- RECORD study results published
During the ADA's annual meeting, the long awaited study results of the RECORD trial were finally published. The study that should have put the issue to rest showed absolutely no difference in cardiovascular issues with Avandia. In addition, patients who used Avandia had improved diabetes control and less use of insulin. At the previous years ADA meeting, two other randomized studies (ACCORD and VADT), which both used Avandia extensively also showed no issues related to Avandia. Given RECORD, ACCORD, ADOPT, DREAM and VADT there have been randomized, controlled trials of 26,000 patients that have been studied over 4 to 5 years, of which more than 15,000 patients took Avandia and showed absolutely no difference in heart attacks. Yet, critics (mainly Nissen and Graham), still had their doubts. The FDA decided that they would meet in July 2010 to review all the newest data and re-look at the controversial issue of Avandia.

February 2010- Grassley releases investigation of FDA and GSK
As above, Sen. Grassley called for an investigation back in 2007, and it took three years to finally release his findings. The report is an indictment of both the FDA for not taking Avandia risk seriously and GSK for hiding data from the public. Interestingly, the report fails to mention any of the studies published since May, 2007 showing Avandia to be safe. It as if time stood still in the Grassley report. The other issue that the Grassely report raises is the ethics of the TIDE study. The TIDE study, which the FDA requested GSK perform is a head to head study comparing Actos and Avandia in regards to safety. Grassely contends that since Avandia risks are known, the TIDE study is unethical and should not be performed.

June 2010- Nissen and Graham take one more shot
In conjunction with the June ADA meeting and weeks before the July FDA advisory committee, both Dr. Nissen and Dr. Graham have separate publications once again questioning Avandia's safety. (Both claim publicly that the timing of the release of this data is coincidental). The Nissen study is an update of his 2007 study, which both addresses some previous criticism of the original study and adds new data, including the RECORD study. Since this is virtually the same study as he did in 2007, it is not surprising that his findings are the same. The Graham study analyzed Medicare claims databases comparing Actos and Avandia. Graham claimed that Avandia was far riskier than Actos when looking at stroke, heart failure and death. Retrospective reviews of databases are legitimate forms of research, but have even more limitations than meta-analaysis. More interesting (which no media seems to be reporting on) is that Graham's study showed no difference between Avandia and Actos when it came to heart attacks. Stroke had never been a question, and even Nissen's analysis showed Avandia didn't increase death; CHF is a risk for both with multiple studies suggesting the risk is similar. Nonetheless, both studies got major media attention, overshadowing a 3rd study presented at the ADA (analysis of BARI-2D) which showed Avandia prevented stroke, heart attacks and death!.

July 2010- FDA Advisory Commitee
The FDA will review all the data mentioned above and hopefully come up with some conclusion. The meeting was planned in advance of Sen. Grassley's report, and was timed such that RECORD, BARI-2D and Graham's review could be incorporated with existing data. Expect debate to be particularly heated.

What are the possible outcomes?

Avandia Gets Pulled from the Market ( Odds 30-1)

This would also be the end of the TIDE study. This is a relatively unlikely scenario given that, with the exception of Graham's retrospective reivew, the only new data since 2007 are RECORD and BARI-2D, which are large, randomized prospective trials specifically designed to look at cardiovascular safety, both showing no issues with Avandia. Another intersting aspect, (which I blogged about in Rough Times for New Diabetes Drugs: The Diabetes Conspiracy Part III) is that because of the Avandia scare, the FDA developed new criteria requiring that ANY new diabetes drug that gets approved by the FDA must first show that it does not cause heart attacks. Specifically, the FDA now requires randomized clinical trials that show a drug does not cause heart attacks with the upper limit of confidence of 1.3. In other words, there needs to be 95% certainty that a diabetes drug couldn't possibly increase the risk of heart attacks by as much as 30%. The confidence intervals for the RECORD trial for heart attack fall under 1.3. Thus, Avandia has already fulfilled the FDA's own criteria of being a safe drug in regards to heart attack. How could they possibly pull it?

That said, removal of Avandia is not impossible. Folks like Graham, Nissen and Grassely have a lot at stake in this game. Avandia staying on the market might make them look pretty bad. Rest assured that they will not go down without a fight.

Avandia is exhonorated (10-1)

Given the results of RECORD and BARI-2D, along with analysis of the VADT and ACCORD trials and multiple data bases, the FDA could be so overwhelmed with Avandia safety data that it proclaims Avandia to have no risk of heart attack and pulls any mention of this from its label. However, with all the surrounding controversy, this seems a little unlikely. The FDA has been harshly criticized for being soft on safety. That said, the FDA might want to take a stand against outsiders (Nissen, Grassley) as well as insiders (Graham) trying to do their job for them.

Nothing Happens (1-1)

This is the most likley scenario. There are no clear winners or losers, so everyone can save face. In this scenario, the TIDE study would likely proceed as planned, but not necessarily. The problem with this scenario is that it leaves physicians and patients in the dark. Is Avandia safe or not? The FDA owes the public an actual opinion, unlike its stance in 2007, which essentially was "we dont' know." In this scenario, the devil is in the details. The FDA will have to update Avandia's label with regards to the cardiovascular safety . The label could be harsher towards Avandia (i.e. more studies suggest concern), reassuring (i.e. despite one meta-analysis a multitude of randomized trials show safety) or neutral.

Actos vs. Avandia?

Finally, I have been asked multiple time about Actos vs. Avandia regarding safety. The conventional wisdom is as follows: even if there probably isn't any cardiovascular risk with Avandia, why would you not just simply switch to Actos just in case? Why do we even have Avandia on the market if Actos exists?

I use both Acots and Avandia, and do believe there is a role for Avandia. There are two important things to consider with regards to this issue:

1. The absence of evidence does not equal the evidence of absence.
In other words, just because no concerns have been raised with Actos does not make it necessarily a safer choice. The vast majority of large, randomized clinical trials (the gold standard of science) have been done with Avandia and not Actos. Avandia beats Actos in trials almost 2:1. It would be like saying 5/10 studies show drinking Coke causes obesity in teens, but 0/5 studies show that drinking Pepsi does not cause obesity; therefore, we should have all teens drink Pepsi instead of Coke to avoid obesity. Some have argued that the reason there has been no signal seen in Actos is because of differences regarding each drug's affect on lipids, with Actos having slightly more benefit than Avandia. However, there has been no true head to head trial of both (which is why the TIDE trial would be scientifically beneficial), and the lipid data varies from study to study (cholesterol actually increased in Actos' one large, randomized trial called Proactive). Furthermore, since there are many more large, randomized trials with Avandia, none of which show an increased cardiovascular risk, one could make the argument that Avandia is the "safer" choice. I am not suggesting that Actos is dangerous. However, stating that Actos is a safer choice is not scientifically valid. The American Heart Association and the American College of Cardiology came to similar conclusions, stating no safety difference between the two products in their recent review of all the data (which was released ahead of schedule in response to the scathing Grassley report).

2. In my experience, the most effective dose of metformin is 1000mg twice daily. The most effective dose of each TZD is the maximum dose. If used early in the disease process, the typical side effects (edema) have been minimal, even at the maximum dose of each TZD. Thus, in my opinion, the perfect dose of Avandamet ( a product which combines Avandia and metformin) is 4/1000mg twice daily and the perfect dose of ActoPlusMet would be 22.5/1000mg. Avandamet is available in this does, ActoPlusMet is not. To give this dose of ActoPlusMet, patients would need two separate prescriptions, two separate pills, and two separate co-pays.

Addendum 7/9/2010
The FDA just posted the preliminary documents for next week's Avandia "smackdown."
A few tidbits:

1. I mentioned three possibilities for Avandia's fate: removal, label revision or no change. There is actually a little more subtlety regarding the label change. They might either remove altogether any mention of heart attack, add more warnings (such as recommending Avandia only be used if other meds fail), or add more warning AND restrictions to prescribing. See the FDA's exact wording below:

A. Allow continued marketing and revise the current label to remove the boxed warning and other warnings regarding an increased risk of ischemic CV events, or
B. Allow continued marketing and make no changes to the current label, or
C. Allow continued marketing and revise the current label to add additional warnings (e.g., contraindications for certain patient populations, recommendation for second-line use in patients intolerant of or uncontrolled on other anti-diabetic agents); or
D. Allow continued marketing, revise the current label to add additional warnings, and add additional restrictions on use (such as restricting prescribing to certain physicians or requiring special physician and patient education)
E. Withdrawal from the U.S. market.

2. One of the presentations regarding the TIDE study, talks about the importance of large randomized controlled trials, citing all the bad things we would still be doing without the data. I love this....

If modern medicine relied on epidemiologic data, administrative databases, & meta-analyses of small trials to identify effective therapies, we would be …
routinely using HRT (WHI)
suppressing VPBs post-MI (CAST)
doing internal carotid artery bypasses (EC-IC study)
using alpha blockers to prevent stroke (ALLHAT)
giving estrogen to men with CAD (CDP)
giving high-dose GIK infusions in the CCU (CREATE)
using perioperative beta blockers (POISE)

2. There is going to be considerable time spent on poking holes in the RECORD study, which is really the pivotal evidence for Avandia safety. One of the main criticisms of RECORD is that the expected number of events (which determines how many patients they need in a study) was much lower than expected. Some has therefore stated that RECORD was "underpowered" to show Avandia is safe. In fact, the AHA/ACC consensus statement hinges its findings on this. However, the study was indeed powered to show Avandia is safe. The FDA presentation looking at this issue confirms this stating "Despite the initial over-estimate of events, the trial had substantial power to achieve its specified goal." This bodes well for Avandia.

3. Dr. Unger, a cardiologist from the FDA states that "the results of RECORD do not substantiate the findings from the Nissen/Wolski meta-analysis on myocardial infarction and cardiovascular death." In other words, from a cardiologist's perspective, RECORD proved Nissen wrong.

4. Nissen is not going down without a fight. Nissen main tactics seem to be 1) poke holes in the RECORD study and 2) present Actos (using non-head to head comparisons, meta-analyses, and claims databases) as a much safer alternative. Again, note that Takeda (makers of Actos) fund his research.

Boston Doctors Getting Paid to Switch Patients to Generics

2010-06-19T11:25:00.000-07:00

Interesting video from WCVB in Boston about doctors getting kick backs from the insurance company to switch patients from branded medications to generic medications. New Rules To Protect Prescription Drug Customers

If people were concerned about undue influence when drug companies used to give physicians pens and other novelties (now currently banned by most companies), they should really be concerned about actually monetary payments. The patient interviewed in the Boston piece stated his doctor wanted to switch him from Lipitor to generic simvastatin (cholesterol lowering medications) but did not mention that he was being payed by his insurance company to do so.

Though this is the first case I have heard of doctors being incentivized to switch patients to generics, it happens in pharmacies all the time. What is horrible is that some pharmacies may switch patients to alternative medications even if that switch costs the patient more money. The example I am familiar with is albuterol inhalers (see FDA Announces End for CFC-Propelled Inhalers).

Switching to generics is itself not a bad things. I have blogged before that, for most medicines, generics are just as good as brand name medicines. For example, if the patient were on Zocor, a switch to the generic simvastatin would probably make a lot of sense, since the medications are basically equivalent and it would likely save the patient some money. However, in some cases, the small differences may actually make a difference. Back in November, I discussed this in more detail (see Generic and Therapeutic Substitutions ).

In this particular case, the therapeutic switch from Lipitor to simvastatin might have been devastating since Lipitor is a much stronger medication. The piece does not say what dose the patient was on, but if the patient required Lipitor 40mg or 80mg, no dose of simvastatin would have given him the cholesterol lowering he needed.

What should you do?
1. If you are on a branded medication, ask your doctor if there is a generic equivalent of the exact same medicine, or one that works just as well.
2. If you are on a branded medicine and asked to switch to a generic by your doctor, find out why he or she wants to switch.
3. If you are on a branded medicine and asked to switch to a generic by your pharmacy, find out why they want you to switch. Is your insurance company asking for the switch? Is the medicine the same (generic substitution) or slightly different (therapeutic substitution)? Regardless, make sure that you check with your doctor before switching any medicine.

Watch Your Step When Changing Asthma Medications

2010-06-15T05:54:00.000-07:00

Back in February, I blogged about the FDA's recommendations regarding long acting beta agonist (LABA) safety (see FDA Blows it on LABA Safety ). A few weeks ago the FDA finalized these recommendations. Though some make sense, such as not taking a LABA without an inhaled corticosteroid (ICS), the main one I have a problem with is the following recommendation for patients controlled on an ICS/LABA combo like Advair or Symbicort:

"Once asthma control is achieved and maintained, patients should be assessed at regular intervals and step down therapy should begin (e.g., discontinue LABA), if possible without loss of asthma control, and the patient should continue to be treated with a long-term asthma control medication, such as an inhaled corticosteroid."

Though the language is a little better than the original version which stated that "LABAs should be used for the shortest duration of time required to achieve control of asthma symptoms and discontinued, if possible, once asthma control is achieved," The notion that stepping down the LABA is preferred to stepping down the dose of the ICS is not evidence based.

As mentioned previously, all the controversy come from the SMART study published back in 2006 which looked at the safety of salmeterol. The study was stopped early because certain subsets of patients, particularly African Americans, seemed to have increased risk, including asthma death. However, the data from the SMART study was very clear that most of the problems came from asthmatics taking LABA's alone. More importantly, there were no increased problems (regardless of ethnicity) when using a LABA with and ICS. The ICS seems to protect against rare, but serious problems associated with LABAs. In fact, no one taking Advair or Symbicort equivalents in the SMART study died.

The FDA, acknowledging that some patients need ICS/LABA's to control their asthma, but concerned about any potential LABA safety issue, recommend step down care for those on combination therapy that are now controlled. Interestingly, the NIH guidelines when discussing step down therapy not only mention that it should be done carefully, as it might risk worsening asthma, but also focus on reducing the dose of the ICS, and not discontinuing the LABA.

The fact the FDA (whose job it should be to tell whether or not a drug is safe or effective) has clinical recommendations that seem to contradict the NIH (whose job it is to make clinical recommendations) is enough to cause concern. However, even more startling is that fact that the data shows that the FDA is clearly wrong. As mentioned in my previous post,
one study in the US of 647 patients controlled on Advair did worse when stepped down to ICS alone, and another French study of 467 asthmatics studied over 6 months showed that stepping down to a lower dose of Advair was fine, but stepping down to ICS alone (what the FDA recommends) caused problems. Today, a new study was just published confirming the same thing: stepping down the LABA is ill advised in a well controlled asthmatic. The study, published ahead of print online, looked at two large managed care databases over several years. They found 4350 asthmatics who stepped down from Advair: 3881 stepped down to a lower dose of Advair and 469 stepped down to the ICS alone (what the FDA recommends). When they matched the patients for age, demographics, etc. they found that the asthmatics stepping down to the lower dose of Advair had 30% fewer prescriptions for short-acting beta-agonists, a 26% lower risk of receiving systemic corticosteroids, and a 48% lower risk of asthma-related hospitalization or Emergency Department visit during follow-up.

Don't take my word for it
If you still remain skeptical, don't take my word for it. Look elsewhere. In Canada, where they have access to the exact same data, the label for Advair is completely different. You can access the full label by clicking here. However, the following excerpt says it all:

"Patients should be regularly reassessed so that the strength of ADVAIR® they are receiving remains optimal and is only changed on medical advice. The dose should be titrated to the lowest dose of fluticasone propionate at which effective control of symptoms is maintained."

In other words, the Canadian Advair label is consistent with what the evidence shows, and consistent with what our own NIH guidelines recommend. The FDA's versions is the opposite.
In the UK, the safety information not only has no mention of stepping down, but their is also no "black box" warning or even mention of the SMART study. The Brits only mention SMART when discussing Severent.

Bottom Line: The LABA safety issue is more about politics then science. LABA's should not be taken alone, but in combination with and ICS (like Advair and Symbicort) are the most effective agents for asthma and are completely safe. The goal for any physician is to have the patient on the lowest amount of medication possible to keep their condition under control. For asthmatics well controlled on ICS/LABA, the data is crystal clear. Despite what the FDA says, it is better to go to a lower dose ICS and remain on an ICS/LABA combo, then to go off the LABA and remain on the ICS alone.

Should You Friend Your Doctor??

2010-06-09T16:17:00.000-07:00

My friend and colleague Katherine Chretien has a provocative Op-Ed in USA Today entitled A doctor's request: Please don't 'friend' me which asks the question whether doctors and patients should interact in social networking sites such as Facebook. Social networking has huge potential in health care regarding the sharing of information and ideas, and could possibly even enhance communication between doctors and patients. However, as Dr. Chretien points out, many physicians have steered clear of social networking sites, and those who do, "actively dread having a patient add them as a friend." The main problems with social networking and patient-physician interactions boils down to confidentiality/security and boundaries.

Confidentiality/security is less murky issue to deal with, and is applicable to all online communications between doctors and patients. First, there has to be privacy. If a patient wants to post their entire medical history to the world, they have every right to do this, but doctors have to ethically and legally maintain a patient's privacy. This should not be too difficult, but could get tricky in a social networking world. If a patient posts "Not feeling well today," a reply from their physician "don't forget to take your meds," would likely be a violation of privacy and confidentiality. In addition, all online communication must be secure. Regular email does not even meet that requirement. In fact, unlike email, both parties need to be logged in to Facebook to send and receive messages, making Facebook a better choice for direct communication between doctors and patient then regular email. Part of security also means encryption. According to Facebook they "always posts to a secure page when users are logging in and employs industry standard encryption."

The bigger problem has to do with boundaries. The doctor and patient relationship is unique in that is should be close and personal, but if too close, the doctor's objectivity could be compromised. This is why it is considered unwise (and sometimes unethical) for physicians to treat their relatives. According to Dr. Chretien, "the thought of opening up our personal pages filled with family photos, off-the-cuff remarks and potentially, relationship status and political and/or religious views to our patients gives us the heebie-jeebies." However, is having family photos online any different than having family photos in one's office? Does an off the cuff remark revealing a physician's political slant any different in the office than on the web? Physicians are often known to personalize their office space with items of personal importance and significance. Family photos, an artifact from a vacation, a golfing trophy, a treasured gift from a patient, etc. I believe this is a good thing. It humanizes physicians and hopefully assists patients in making connections with us.

The two problems with Facebook are controlling one's own privacy and the use of the word "friend." Facebook was founded by Mark Zuckerberg with his college roommates and fellow computer science students. In other words, it was invented by kids. The term used to link one another is "friend." However, this is not "friend" the noun which we are all familiar with, but rather "friend" the verb. Though "friend" the verb can theoretically used to mean "befriend," in conjunction with Facebook it is the mechanism by which one connects with another individual online. The confusion is not unique to the doctor-patient relationship. I am sure many young adults wonder what to do when a parent "friends" them. If instead of "friend", Zuckerberg and colleagues had used the word "connect', we would probably be less concerned about boundary issues. Is it wrong for a physician to "connect" with patients online?

The issue of controlling one's own privacy is likely what truly concerns many physicians when considering using social networking platforms like Facebook with patients. After all, the physician who personalizes his or her office space has carefully decided what he or she wants patients to know about them. Even if a physician is careful in posting information on Facebook knowing that patient-"friends" might see, other non-patient "friends" can tag the physician in a compromising photo or leave an inappropriate reply that could be easily viewed by the patient. This is obviously a barrier, but this barrier is easily overcome. The easiest way to avoid this problem is to have two separate Facebook accounts: a professional/patient account and a private/personal account. A variant of this would be setting up a "Fan" page. (Please feel free to click on the blue box with the "F" to the right to become a "fan" of Dr. Mintz). Finally, any Facebook user should be familiar with the privacy settings on Facebook. These can be customized. For example, you might create a groups called "patients", "relatives" and "close personal friends"; assigning different permissions to each of these groups.

As the Op-Ed points out, there are currently no national guidelines for social media use by physicians and, as mentioned above, confidentiality and boundary issues are difficult and controlling one's own privacy may not be easy for many physicians. However, most of the barriers for using social networking between doctors and patients can be overcome. Given that, and the potential uses and benefits social networking can provide, I would somewhat disagree with my friend (correct usage of the noun) that physicians shouldn't be "friends" on Facebook with patients. However, if they do, they should proceed with extreme caution.

Fracture Risk and Acid Blocking Medications: What Should You Do?

2010-05-26T05:56:00.000-07:00

Yesterday, the FDA released a Drug Safety Communication warning about a possible risk of increased fractures with acid blocking medications called proton pump inhibitors or PPI's.

PPI's have been a major advance in medical science. Prior to these and ealier medications, the treatment for severe gastroesophageal reflux disease (GERD) was major surgery. PPI's are now commonly prescribed for GERD and less serious heart burn, many are generic, and some are now sold over the counter. The popular PPI's include Nexium (esomeprazole), Prilosec (omeprazole), Prevacid (lansoprazole), and Protonix (pantoprazole) which are available by prescription. Prilosec OTC and Prevacid 24HR are sold over-the-counter (OTC). Given the use and popularity of these medications, this warning may cause great concern among patients who rely on these medications.

What did the FDA find?
The FDA analyzed the data from several epidemiologic studies in thousands of patients studied for several years and in 6/7 studies found a greater risk for certain kinds of fractures when patients took PPI's. These risks seemed to be the greatest when patients were taking the medications regularly, for a long time, and at a high dose.

So is this a real problem?
Maybe. It is important to know that the gold standard of studies is the randomized clinical trial (RCT). Only RCT's can prove a cause and effect. None of the RCT's with PPI's thus far have shown and increase fracture risk with PPI's. The problem with RCT's is that they are hard to do and are usually limited in time (6 months) and have fewer patients. So a rare but serious side effect is unlikely to be picked up in an RCT. The epidemiologic studies are useful, but have limitations (which the FDA readily points out). These studies are case-control, meaning they look for people who had fractures, find similar people who didn't have fractures, and then see how common PPI use was in each group. Though the studies show that people with fractures were more likely to take PPI's than people without fractures, this doesn't mean that PPI's cause fractures. Maybe the folks who took PPI's had stomach troubles and were less likely to take things that prevent fractures like Calcium or Bisphosphates (drugs which prevent fractures but are relatively contraindicated in those patients with GERD). In addition, these studies use claims databases. This means that to get the data, doctors never examined or interviewed patients, rather the investigators looked at insurance claims for fractures, medication use, etc. For example, we don't know what the bone density scores (DEXA) were for the patients in this study. It is very possible (and even likely) that the patients in the fracture group had lower DEXA scores, and this more than the PPI use accounted for fracture. Also, if you have ever received a bill or claim notification from your insurance company, you problem know that the information they contain is not always 100% accurate. That said, the number of patients studied and the consistency of this relationship suggests that there may indeed be a cause and effect.

What should you do?
It is unlikely that short term use of PPI's substantially increase risk of fractures. So if you need an occasional Prilosec OTC (like after a big barbecue this Memorial Day weekend), this is probably fine. If you need to take PPI's, either prescription or over the counter, on a daily basis and have symptoms when you do not take them regularly, this could be a sign of more serious disease and should be investigated by a physician (regardless of a fracture risk). For those patients who have had an extensive medical work up for a stomach condition and told by a physician that taking a PPI on a daily basis for years to come is the recommended treatment, then they should discuss the risks and benefits of PPI's as it relates to fractures. This would be particularly important if you have an increased risk for fracture such as a previous fracture, family history of osteoporosis, or low bone density.

Lipitor or Crestor for LDL's above 160

2010-05-14T13:08:00.000-07:00

I just read A systematic review and meta-analysis on the therapeutic equivalence of statins. This artilce will not make any major U.S. headlines because it is a Taiwanese study from a not very well known journal. However, the methodology is sound and makes an important point to patients who need a statin and are deciding between a generic and more expensive brand name medication.

The study did a systematic review of all the studies which compared the different statins. They found that at comparable doses, statins are therapeutically equivalent in reducing LDL (or bad cholesterol). This would suggest that if statins are essentially equal, provided you use the right dose, then you should always go with a generic. However, the other thing they found was that "the only two statins that could reduce LDL-C more than 40% were rosuvastatin and atorvastatin at a daily dose of 20 mg or higher." In other words, those patients who need cholesterol lowering drugs and have to get their cholesterol down by less than 40% should be OK with generic, but those who need to get their LDL cholesterol by more than 40% should use either Crestor (rosuvastatin) or Lipitor (atorvastain). Though new guidelines should be out by the end of the year, current guidelines suggest that patients with increased risk for heart attack and stroke (all diabetics, mulitple risk factors,etc.), who are generally the patients we use statins in, need their LDL's under 100. This means that if you are at increased risk for heart attack and stroke, and your LDL is 160 or above, you should not take the generic (even if it is cheaper), but take the more expensive branded cholesterol medicines.
Fortunately, as I mentioned in a recent post Are Drug Reps and Free Samples Bad For Patients? It Depends, both companies offer coupons to offset the additional out of pocket costs, so you should not pay much more for Crestor or Lipitor than what you would pay for a generic medication.

Are Drug Reps and Free Samples Bad For Patients? It Depends

2010-05-03T19:09:00.000-07:00

One of my favorite blogs, KevinMD, featured a post by Internist and fellow blogger Dr. Leslie Ramirez (founder of Leslie’s List, which helps the uninsured and underinsured find more affordable medications and health care services) on the true cost of free drug samples. Her point was that "free" drug samples may cost a patient in the long run if they are followed up with an expensive prescription that the patient can't afford. I posted a response on Kevin's site (more below) stating the issue was a little more complex, as Dr. Ramirez' example applied specifically to a patient who was paying out of pocket for medications, which is not usually the case. However, this post received numerous responses about the value/evils of both drug reps and the samples they provide. Below is an edited/expanded version of my replies.

The Benefit and Harm of Reps and Samples
Do drug reps/free samples…
-influence doctors? Absolutely.
-increase prescribing of non-generic meds? Absolutely.
-contribute to health care dollars spent on meds? Absolutely.
-harm or are bad for patients? It depends.

It is true that whenever a generic medication has equal safety and efficacy as a branded medication, the patient and public benefit when a generic is used. However, just because there are generic medications available, does not always mean that generics are the best choice for patients.

A good example is type 2 diabetes. The RECORD (see For the RECORD, Avandia does not cause heart attacks) study looked at cardiovascular safety of the much maligned drug Avandia. (RECORD showed it not to increase risk of CV death or hospitalization-something the media continues to ignore). The study took patients on a generic diabetes medication (either metformin or sulfonylurea) and randomized them to either an expensive, branded diabetes medicine (Avandia) or the other generic. Patients in the Avandia group who still had uncontrolled diabetes on Avandia + one generic could add the other generic. Patients in the other group who were uncontrolled on both generics had to go to insulin.

In addition to showing no difference in cardiovascular safety (primary endpoint), the patients in the Avandia group had better diabetes control, less weight gain, better cholesterol profiles, less hypoglycemia and less insulin use. In other words, though it certainly costs more money, (in this study) it was better to add Avandia then sticking with only generics. This should not be surprising since we know that the older diabetes drugs fail after a few years, and that TZD's like Avandia (seen now in ADOPT, RECORD, and BARI 2D) sustain glycemic control.

There are a few other examples where generic products exist, but branded products may be better. Branded statins (Crestor, Lipitor) are likely better then generics for patients with high cardiovascular risk who need to get their LDL (bad) cholesterol down more than 40%. In hypertension, losartan is the first generic angiotensin receptor blocker (ARB). Though there are several ACE inhibitors that are good once a day generics (lisinopril), up to 10% of patients will get a cough and need to be switched to an ARB. Now we finally have a generic ARB, except this one is not nearly as good as the other 4 branded products on the market. Because insurance companies will likely make it very difficult (higher co-pays and prior authorizations) to get one of the branded ARB's, patients will likely need to get a cough on an ACE and then fail losartan, before they are allowed to use the newer, better ARBs (and will still have a very high co-pay).

In addition, there are many medications that have no generics. All the respiratory medications (Advair, Symbicort, Spiriva, etc.) essentially have no generic equivalent. Having a drug rep provide samples of these meds will (as stated above) certainly increase prescriptions and therefore increase healthcare spending. However, asthma kills about 11 patients a day, COPD is the 4th leading cause of death, and both conditions are substantially under treated. Writing more prescriptions of these medications, and thus the reps that provide them, should therfore be a good thing. Even if the medicines are costly, their increased use will prevent exacerbations, hospitalizations, and even death (which have their own costs).

There is also the issue of direct cost to the patient (out of pocket costs) and the convenience factor. The FDA just approved a combination pill of Nexium and Naprosyn for rheumatoid arthritis. Many patients with rheumatoid arthritis need to take NSAIDs like naproxen on a regular basis. One of the side effects is stomach ulcers. Acid blocking proton pump inhibitors (PPI's) like Nexium can prevent these ulcers and guidelines recommend the use of PPI's with chronic NSAID therapy. The newly approved, branded pill will be an expensive, once a day pill that will treat the arthritis and protect the stomach. However, Prilosec (another PPI) and Naprosyn, are both over the counter. Why not just take two over the counter pills a day instead of an expensive branded pill? CVS brand naproxen would cost about 10 cents for two 22omg pills (prescription dose is 500mg), and one Prilosec 20mg OTC (not as strong as Nexium, but should do) is about 70 cents a day. Thus, a patient needing NSAIDs and stomach protection would need to take 3 pills at 80 cents/day, or $24/month. However, it is very likely that the drug company will provide coupons for patients that guarantee them that their co-pay is no more than $25/month. I would think that most patients would prefer the better, once a day pill than the 3 pills a day for about the same price. (There is also a potential safety benefit as combining the pills ensures the stomach is protected when taking an NSAID).

As already alluded to, the issue becomes further complicated when insurance coverage, samples and coupons create complex equations where decision making becomes a challenge. One example would be high cholesterol. Let’s say your bad cholesterol or LDL is 160 and your doctor tells you it needs to be under 100 based on your risk for heart attack and stroke. Simivastatin is generic and has been proven effective, but you will likely need the highest dose of 80mg to get to your goal (the higher the dose, the greater the likelihood of side effects). Generic simvastatin (no samples) costs you $10 month at your local CVS. There is also Lipitor, a branded drug that will get you to goal at a 20mg dose, but at a price of $25 per month. However, I can give you a four week sample of Lipitor to try (to make sure there are not side effects, etc.) and a coupon that will lower your monthly cost to $15. This will last for a year (at which point Lipitor should be generic). Using the branded product with samples and coupons, the additional out of pocket cost to the patient is only $50/year or an extra $4/month, but they get to try the med first, and received a drug that worked better, with fewer side effects. Which is better for the patient? (Before you say that $50/year is a lot for a poor person, keep in mind that very poor patients are on Medicaid and won't pay any difference for the medications, and people who do not have prescription coverage might have problems being able to afford either, as generic simvastatin 80mg is $33/month).

To be fair, there are PLENTY of examples where branded drugs are promoted heavily by the industry using drug reps and samples, where an equally safe and effective medications are available generically. Dr. Ramirez' post regarding generic citalopram and Lexapro is a great example. In addition, the argument can be made that drug companies should be putting their resources coming up with useful new agents, rather than re-packaging older medicines into one pill (like Naprosyn and Nexium).

The point is that the issue of the samples, drug reps and the industry is a complex one. The drug industry is one of the most profitable industries in the US. Their use of expensive, direct to consumer advertising may seem inappropriate to some, when so many in our country can not afford medications. Past excesses of lavish gifts to physicians (no longer allowed) and more recent settlements of off label promotions (see Pharma Should Not Settle Off-Label Promotional Suits) has certainly eroded trust in the industry from the public, patients and many physicians.

However, drugs save lives. Even in recent years, we have seen the remarkable difference prescriptions medications have made (HIV, cancer, heart attacks). Also, the majority of prescriptions being used today are now generic, and were made possible because they were once sold under a brand name. As stated above, generics are not always the best choice for patients, and while drug company promotional efforts will undoubtedly increase sales of expensive drugs, this is not necessarily a bad thing if patients' lives are improved. Finally, the way medications are covered and paid for create a sometime perverse set of circumstances where samples and coupons for expensive medicines may actually be in the patient's best interest even if similar medications are available generically or over the counter. Many (especially in the media) want to paint the influence of the pharmaceutical industry as black and white. However, this issue remains very, very grey.

Pharma Should Not Settle Off-Label Promotional Suits

2010-04-28T05:36:00.000-07:00

Major headlines were made when it was announced that AstraZeneca Settles Case Over Marketing of a Drug For $520 Million. This is not the first and will not likely be the last off-label settlement by a drug company. The charges from the Justice Department , which the company denies, claim that Astra Zeneca (from Med Page Today) paid doctors for "ghostwritten journal articles that the named authors did not write and reported studies they did not conduct" and "to give promotional lectures to other health care professionals about unapproved and unaccepted uses" for their drug Seroquel (quetiapine) which is used to treat bipolar disorder. Though ghost written articles may not be the best way to promote your product, they are not illegal. In addition, paying physicians to speak about a product is an FDA approved way for drug companies to discuss their products with practicing providers. These activities were not the problem, its that (the Justice Department claims) they were off-label, not on label promotions.

I blogged about what is meant by labeling a while ago in a post called An Indication For Change. Briefly, a physician can prescribe any FDA approved drug for any reason they want. However, a drug company can only promote (sell) that drug for what the FDA says it can be used for. A great example would be Crestor. Back in November of 2008, I blogged about the results of the Jupiter trial (see Jupiter is Out, and the News is Good! ), which showed that in patients who had relatively normal cholesterol levels but high CRP levels, 20mg of Crestor reduced the risk of heart-related death, heart attacks and other serious cardiac problems by 44%. This was a large, randomized clinical trial with important information and the first real trial showing major benefit when a statin was used as primary prevention for heart disease in people with normal cholesterol levels. Despite the exciting news, the Crestor drug reps couldn't talk about it, even though the study was published, and the results were headlines in every major media outlet. This would have been considered off-label promotion. It wasn't until February 2010, when Crestor was approved for primary prevention of cardiovascular disease by the FDA.

I will admit that I do not write Seroquel, and told many of the AZ drug reps who tried to get me to use this drug, that Seroquel was not really a primary care drug, and they would be better off spending their time speaking with the psychiatrists. However, though I am certain one or two rogue drug reps probably bent the rules here and there, given the previous large settlements by other drug companies, I find it very hard to believe that AZ systematically promoted Seroquel for off-label use. As stated AZ denies these claims.

If this is indeed the case, then I believe AZ should fight the claims by the Justice Department, rather than just pay a fine. If you are really innocent, then you will try to prove your innocence at any cost.

As a physician, I understand what settling a case means. The vast majority of malpractice claims are settled. This is because doctors get nervous when their fate is left to a jury to decide between the rich doctor and the injured patient. For physicians, especially given the cost of litigation, it often makes more sense to settle, admitting no wrong, and get on with your practice then to prove your innocence. However, with pharma's deep pockets, cost should not be an issue. Every time a drug company settles a claim for off label promotion, it is saying to patients and physicians "we are not to be trusted." As part of their settlement, AZ will likely have to send "Dear Doctor" letters to all physicians essentially admitting guilt.

Interestingly, The Wall Street Journal is reporting in a post Whistleblower Twice Over: First Lilly, Now AstraZeneca, that the same person who reported AZ to the government (and will pocket $45 million) previously blew the whistle on Eli Lilly who settled a $1.4 billion for off label promotion (he pocketed up to $100 million for that). The fact that the same person blew the whistle on two companies for the same charge (in my mind) calls the entire off-label promotion scheme into question.

This will not be the last big settlement for off-label promotion. The government makes big bucks on these cases, and the drug companies just write a check when fined. If pharma really want to show physicians, patients and the public that it is just trying to make useful medications to help people and not trying to make a profit any way they can, they should fight these claims as hard as possible.

Where have all the journalists gone? More bad reporting on Avandia

2010-04-18T20:28:00.000-07:00

I thought journalists were supposed to be impartial, report multiple sides of the story, and only use facts. At least in the case of reporting on prescription medications, Avandia in particular, it seems those "rules" no longer apply.

Today the Wall Street Journal announced that the FDA Weights Halting Avandia Safety Study .
They are basing this report on a Letter written to Sen. Grassley on 3/30 by the FDA commissioner in response to Grassley's findings on the FDA's handling of Avandia. If I were a journalist (and I don't pretend to be one), after reading this letter, the headlines I might have suggested to my editor would have been:

FDA to Grassley: You Have to Wait Until July or
FDA seeks Big Gun in Institute of Medicine to Help with Avandia

Nowhere in the 5 page letter does it say ANYTHING about the FDA considering halting an ongoing study. Here is the particular section that the journalists from the Wall Street Journal are basing their headline on:

"I recognize that head to head safety trials can pose challenging ethical questions. On the one hand, such a trial, by its very nature, must be conducted in the face of a safety concern. One the other hand, if one therapy is clearly inferior to the other, then such a trial should not be conducted, because it would place one group of patients at unnecessary risk."

Though the next paragraph mentions that some experts believe that Avandia is inferior to Actos, the paragraph concludes that some experts, in particular the American College of Cardiology and the American Heart Association, have not come to these conclusions.

I implore you to read the entire letter, and read it in the context that the head of the FDA is writing this letter in response to a Senator who wrote a very public and scathing report on how their operation is run. The report does not read, "thank you senator, we were wrong and will consider stopping this dangerous trial." Rather, what the report actually says is that safety is important to the FDA, in 2005 they became aware of a questionable safety issue but decided it did not warrant going public, when it did (with pressure from Sen. Grassley) the FDA met in July 2007 and decided to keep Avandia on the market, there has been new, more robust data since 2007 which seems to indicate that Avandia is safe, and we have already planned (even before the Grassley report came out) to meet this July to review all the data again.

Read in its entirety, the FDA had already planned to review all of the Avandia data, including the TIDE study in July. The letter to Grassley, that the Wall Street Journal is reporting on, gives no indications that these plans have changed or that the FDA is now considering stopping an Avandia study. If anything, in a very subtle way, the FDA is telling Grassley why the study is needed.

Bad reporting on this subject is not new. In my post More Avandia Scare- Again, Unwarranted back in February, I wrote about New York Times piece that broke the story on the Grassely report. While I do believe the story was worth reporting, the Times failed to mention that everything in the report was from 2007. Both the Grassley report and the Times failed to mention that there was new data, specifically the RECORD trial (see For the RECORD, Avandia does not cause heart attacks, Avandia Vindicated, ) which seems to exhonerate Avandia from any heart risk. This is the real story, that a good diabetes drug continues to get bashed in the media, when a very well done study presented almost a year ago has shown in to be safe.

As referenced above, I believe the real story in the FDA commissioner's letter to Grassley is the fact that they are asking the Institute of Medicine to look into the matter. More importantly, they seem to indicate that the IOM's report will be ready by the July 2010 advisory board. My read on this is that the FDA, based on the scientific data available, feels that Avandia is actually a safe drug. However, given the scrutiny and political pressure they are under, likely believes that anything less than a "pull it from the market" recommendation from the July advisory committee will keep it under fire. Thus, they have brought the impartial and well respected IOM on board. The only reason I can think of for doing this is to back them up on a decision in favor of Avandia.

Here's something to think about:
Because of the media storm caused by Avandia, the FDA now requires any new diabetes drug to prove that it does not cause heart attacks before being approved (see Rough Times for New Diabetes Drugs: The Diabetes Conspiracy Part III ). These criteria are not surprisingly pretty strict. Based on the results of the RECORD trial, Avandia has now met this new standard of cardiovascular safety, now required of all new diabetes drugs. How will the FDA be able to continue to say that there might be a risk, let alone pull the drug and stop a safety study, when Avandia has now met the FDA's rigid cardiovascular safety criteria?

Read "The Estrogen Dilemma" With Caution

2010-04-16T05:27:00.000-07:00

There is a piece in the New York Times called "The Estrogen Dilemma" which many women will read with great interest. I would urge women to read this with great caution before jumping to any conclusions.
The article is a well written piece by journalist Cynthia Gorney, who discusses both the controversy of hormone replacement and possible benefit with memory and mood, simultaneously with her own personal medical history. I would imagine many women readers will identify with both Ms. Gorney's depression (since it is so common) and her struggle with the decision whether or not to stay on hormone replacement (since there is so much confusion around the issue).
The article pokes many holes in the landmark Women's Health Initiative (WHI). Prior to this study, many physicians, myself included, were prescribing hormone replacement to perimenopausal and post-menopausal women like candy. We did this because the data on the purported benefits seemed robust, and the data on risks seemed minimal. The WHI proved that making routine decisions without large, randomized clinical trials was not necessarily a good idea. The WHI showed that, at least in the population studied, the risks of hormone replacement (breast cancer) outweighed the benefits (heart attacks turned out to be a risk not a benefit). More importantly, many doctors stopped prescribing hormone replacement because alternatives to protect against heart attacks (statins, aspirin) and osteoporosis (bisphosphonates, calcium, vitamin D) existed and didn't carry the same risks. However, this doesn't mean that the risks/benefit ratio for hormone replacement applies to every women equally. Women who suffer from severe symptoms of menopause, especially with a low risk of breast cancer, would certainly have a risk/benefit ratio favoring hormone replacement.
Gorney's article suggests that perimenopausal mood issues such as depression, memory/attention, as well as prevention of Alzheimer's disease can all be linked to estrogen deficiency, and estrogen replacement just might be the solution. These facts coupled with very real holes in the WHI data regarding women in their late 40's and early 50's (who weren't in the study), suggests that hormone replacement may in fact be just what many women need.
However, the key is the lack of data. Though studies are underway, we do not know whether or not estrogen can help with perimenopausal mood disorders, or even if it does, whether it is any better than other treatment such as anti-depressants. In addition, though there is reason to believe that the dangers found in women in the WHI might not apply to younger women, we do not have data to prove that it is safe. Absence of evidence is not the same thing as evidence of absence (harm).

Bottom Line: Medicine has to be individualized. Every therapy and test, including screening tests like PSA's and mammograms, have risks and benefits. Balancing those risks and benefits is important, and is not the same for every patient. Age, individual risk for disease, personal preference, and symptoms are all important factors. Estrogen may have an important role in mood disorders and memory for women, and may be safe if started in the late 40's and early 50's, but we simply don't know for sure. Estrogen, especially when given with progesterone is definitely linked to breast cancer, and given later in life, increases the risk for heart attacks. If you are a perimenopausal women that identifies with Ms. Gorney, and you think that estrogen replacement may be the miracle cure you are looking for, proceed with caution. Weigh all the available data, risks and benefits before jumping to conclusions from a very well written and emotionally impactful article. Your physician can be very helpful in guiding this decision.

FDA Announces End for CFC-Propelled Inhalers

2010-04-14T09:19:00.000-07:00

As reported in Med Page Today, the FDA Announces End for CFC-Propelled Inhalers. Of the seven inhalers with deadlines for removal, only three are still being made:

Flunisolide (Aerobid Inhaler System) on June 30, 2011
Albuterol and ipratropium combination (Combivent Inhalation Aerosol) on Dec. 31, 2013
Pirbuterol (Maxair Autohaler) on Dec. 31, 2013

The reason for this is because CFC's are harmful for the environment, and the newer inahlers have to be replaced with a different, more environmentally friendly propellant called hydroflouroalkane or HFA. I have blogged about this previosuly (please see Asthma inhalers and More on Asthma Inhalers ).

According to the FDA, "patients using the inhalers scheduled to be phased out should talk to their health care professional about switching to one of several alternative treatments currently available. Until then, patients should continue using their current inhaler medication."

What you should do:
1. Albuterol If you are taking albuterol, please see my earlier posts. I still have patients that have their very old albuterol canisters, which are probably no longer effective. An important thing to know is that there is no longer any generic albuterol. More importanly, if your physician writes a prescription for albuterol, the pharmacist will likely give you ProAir, which may or may not be what your insurance prefers and/or what is least expensive for you. This is because many of the chain pharmacies are getting a kick back from the makers of ProAir. Make sure your provider writes for the correct inhaler. All things being equal (same co-pay for patients), I recommend Ventolin HFA (because it is the only one with a dose counter) or Xopenex HFA, because of diminished side effects. NEW INFORMATION: GSK, makers of Ventolin HFA sell a $9 inhaler, regardless of your insurance. Though the inhaler has fewer puffs in it, if you are using your inhaler that frequently, then your asthma is not under good control, and you should be on a different controller medication. Ask your doctor for Ventolin HFA 60 (they have to write the 60 part).

2. Maxair- Some patients love this drug, but it's going away. Before January 2014, get another albuterol. See above and previous posts for advice.

3. Aerobid- I didn't even realize they still made this medication. It is no more effective then other similar medications, probably less effective, possibly more side effects, and it tastes nasty. If you are on this medication, switch ASAP to another inhaled steroid. Good alternatives include Flovent, Pulmicort, Asmanex, and Alvesco.

4. Combivent- This will likely affect patients the most, since few patients are on Maxair or Aerobid, and there are far more COPD patients than asthmatics. It is very likely that before January, 2014, the makers of Combivent with come out with a Combivent HFA. However, there are reasons to consider switching now. Please see older posts Good News for COPD , Bad news for COPD: Why this meta-analysis should be believed (and the Avandia one should not) , and UPLIFTing News for COPD

Briefly, a few studies have come out which make me very concerned about using Combivent. One study published in the Annals of Internal Medicine studied a VA population and found that patients taking ipratropium had significantly higher death rate of about 11%. A second study was a meta-analysis published in JAMA that analysed date from 14,783 patients with COPD and found that patients taking either ipratropium or tiotropium (Spiriva) or both had a 58% increase in cardiovascular death, heart attack or stroke when compared to patients taking other meds (Advair, albuterol or placebo). Though combined, these studies might cause safety concerns with the entire class of anti-cholinergic inhalers, the UPLIFT trial, a long-term, large randomized controlled trial (4 years, almost 6000 patients) which unfortunately failed to show that Spiriva could decrease that rate of lung function decline, did show about 10% relatively fewer deaths. Thus, though anti-cholinergic medicines may cause some harm, it appears that this is likely mainly for the short acting ipratropium and not for the long acting tiotropium. I would therefore recommend that COPD patients talk to their doctors about stopping their Combivent now and switch to a different controller medication (Advair, Symbicort, Spiriva) and/or switch to albuterol alone as a rescure medication.

FDA too focused on risks compared to benefits when approving drugs

2010-04-08T04:59:00.000-07:00

In my opinion, the pendulum has swung to far in the safety direction when it comes to approving new drugs. Over a decade ago, the reverse was true and medications like Vioxx and Rezulin were approved and prescribed too quickly without either additional studies required before approval or closer follow up after approval. Though a more vigillant approach to safety was certainly needed, now there are many drugs that may never get approval because it appears that the FDA is concerned about virtually any risk at all.

Today, as reported best by Medpage in Panel Votes Against New PDE4 Inhibitor for COPD, despite prior discussions in favor of the drug, the FDA decided not to approve roflumilast (Daxas), a phosphodiesterase 4 (PDE4) inhibitor, for treatment of chronic obstructive pulmonary disease (COPD). Now, I will admit after seeing some of this data, that I was not overly impressed with Daxas. It would never be my "go to" drug for COPD, because we have so many better options such as inhaled corticosteroid/LABA combinations (Advair, Symbicort) and long acting anti-cholinergic agents (Spriva). However, there are still many patients with COPD who take both drugs as well as additional short acting inhalers, and are quite symptomatic. In addition, prior to either of these medications being available, one of the primary treatments for COPD was theophyline, one of the original PDE inhibitors. It had a far worse side effect profile than Daxas (seizures, blood levels needing to be monitored), but was the mainstay of therapy. In fact, there are many doctors still prescribing theophyline today for their COPD; mainly in those patients who can't take or are still symptomatic on the aforementioned inhalers.

Looking at the Daxas data, roflumilast resulted in a significantly greater change in prebronchodilator FEV1, improving it by 48 mL over the course of the study (P<0.0001). This amount of improvement would be minimal for a healthy person or even an asthmatic, but for a patient with COPD, this could be the difference of being able to walk up the stairs or having to live on the first floor. In addition, the number needed to treat to prevent once exacerbation was significant, between 3 and 5. In other words, even though this was not the best medication in the world for COPD, it was certainly beneficial, and would have an important role for patients not well controlled on standard therapy.

Safety concerns were certainly real. A total of 218 cancer/tumor events were reported in 208 patients -- 60% of whom were in the roflumilast group,and 40% of whom were in the placebo group. However, even though there were more cancers in the roflumilast group, many believe these cancers were not caused by the drug because most of the tumors were identified months after treatment, which would be too soon for the drug to have a causative effect. The most common side effect was nausea and diarrhea, and this was the most common reason that the 14% of patients stopped taking the drug. There seemed to be a signal for psychiatric conditions, including suicidality, but again, it is unclear that the drug actually caused this.

Every drug has risks and benefits. My guess is that aspirin would not be approved by the FDA today, since it has an increased risk of GI bleeding, other medications can relieve pain, and the benefit of heart attack and stroke prevention is controversial. The key is to balance these risks and side effects. If there are safer, more effective and similar drugs, then there is no reason to approve a new one. However, in many cases, it is better to have a drug with some known risks associated with it available to patients who have failed other therapies, then to not have the drug available at all. The FDA could have easily approved the Daxas and recommend it for patients who were still symptomatic on more standard therapy. Now, physicians will not have this medication in their tool kit for the select few patients who might actually benefit from the drug.

I believe that because the FDA has come under so much scrutiny regarding drug safety, it has made decisions where risk and benefits were not balanced appropriately. Because of the Avandia scare (which has since been proven to be unwarranted see For the RECORD, Avandia does not cause heart attacks), it is now difficult for any new diabetes drug to be approved. I also recently mentioned how unwarranted safety concerns by the FDA will likely harm far more asthma patients then help (see FDA Blows it on LABA Safety ). When safety or the need to get new drugs on the market is such a major driving force, patients are harmed, regardless of which direction the pendulum is swinging. The safety folks seem to be in the driver's seat and may be harming patients by not giving them access to needed medications. It is time for the FDA to start taking a more balanced approach to approving medications.

No News Usually Good News: Bisphosphonates (Fosamax)

2010-03-28T05:53:00.000-07:00

I was once at a Chinese restaurant and when I opened my fortune cookie at the end of the meal I found no fortune. When I told the waiter, he smiled and said, "no news is good news."
It seems to me, that it least when it comes to reporting on medical news, the media tends to only report on one thing: bad news. Medical headlines are often about a common drug that has now found to be dangerous or what you are eating/doing that will probably kill you. The rare exception tends to be a story about the latest miracle cure (usually with little to no evidence to support it). This is one of the reasons I started this blog: to give a broader, balanced physician's perspective on media headlines; to allay fears or let patients know when they are actually warranted. One of my frustrations with the media has been lack of reporting on additional research after a major story, especially when that research is actually reassuring.

One of the best examples of this has been Avandia. Recently, the media was quick to pick up on a Senate report regarding concerns on the way the company (GSK) and the FDA handled Avandia's safety data. The Avandia story first made headlines in May, 2007 when Dr. Nissen's meta-analysis on Avandia was published the New England Journal which claimed that Avandia increased the risk of heart attack by 43%. However, the media never really covered the RECORD trial, whose results were released in July, 2009 that showed Avandia does not in fact increase heart attacks. Even if they felt it was not necessary to mention the RECORD study in July 2009, it was inexcusable not to mention this when reporting about the recent Senate report, which bashed the drug and it's maker, but failed to mention any of the new, reassuing data.
When I prescribe Avandia to patients, they are still convinced that the drug is dangerous. This is because the media reported the bad news (back in 2007, and more recently with the Senate report), but never the good news. In fact, in response to the Senate report, a group of cardiologist who had been studying this class of medications extensively released their report earlier than planned. This report was extremely reassuring regarding Avandia safety. Yet, there was no mention of this in the press.

The latest example is bone fracture and bisphosphates. I blogged about this last month, when two reports from a medical conference surfaced, and these concerns were given significant media attention, including a Diane Sawyer piece on ABC. The class of drugs is called bisphosphonates and include medications like Fosamax (now available as generic alendronate), Actonel, and Boniva- the drug pitched by celebrity spokesperson Sally Field. These drugs are designed to treat osteoporosis which is a condition where the bones become brittle; but there had been some reports of rare, but serious bone fractures. In my blog post back then, I noted how the FDA was aware of the reports, had looked at the issue, and found no compelling reason to issue a warning. I also noted that most of these fractures occurred in women who had been on bisphosphonates for a long time, and that new evidence suggests five years is enough. After looking into the issue further, I found that there was a population study that suggested there was no link between these medications and dangerous fractures.

Now for the good news! In the current issue of the New England Journal of Medicine, several researchers took this issue head on. They combined the data from large, randomized controlled trials to look for any risk. In the three trials they examined, which included over 14,000 patients, they found no increased risk.

They state, "the occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare, even among women who had been treated with bisphosphonates for as long as 10 years. There was no significant increase in risk associated with bisphosphonate use, but the study was underpowered for definitive conclusions."

This study, along with other information is very reassuring for the millions of women taking these medications, now wondering whether or not they are safe. Why did the media not give this new study even 5% of the attention they gave to some of the initial concerning reports? Why is it that the media reports only when there are concerns about treatment, and virtually never reports about studies that subsequently show that these initial concerns are unfounded? Why does the media feel it can only attract readers/viewers with tales of woe?

Bottom Line: Often you will never hear about good news regarding medical treatments because the media does not cover this information. Ask your doctor, or go online yourself, before completely discounting a recommended medication or treatment due to safety concerns you may have heard about. Regarding bisphosphonates like Fosamax and Boniva, these appear to be safe medications, though I would still not recommend taking for more than 5 years.

Blood sugar, high blood pressure and cholesterol control still important for diabetics.

2010-03-14T18:52:00.001-07:00

The secondary findings of the ACCORD trial reported out today, and already the media is buzzing. Though the news was disappointing, the results are not nearly as bad as some of the media headlines are making it out to be. ABC News is reporting: ACCORD Study: Cholesterol, BP Control Does Little Good for Diabetics and MSNBC states that Intense treatment hopes for diabetics dashed. If I were a diabetic, I might think that controlling blood pressure and cholesterol was not important. However, this couldn't be further from the truth.

The same thing happened when the media first reported that the ACCORD study was stopped.
( See ACCORD and ADVANCE: Good News for Type 2 diabetes...really). This first part of the study was looking at whether or not intense lowering of blood sugar to normal (A1c less than 6%) prevented heart attacks and strokes more than the current standard of care (A1c less than 7%) which had not proven to reduce heart attacks or strokes. The study was stopped early because there were more heart attacks and deaths in the intense group. However, though the media headlines similarly questioned the role of blood sugar control back then, the good news was that the rate of heart attacks and strokes were much lower than expected. In other words, good sugar control in diabetics is likely important in preventing cardiovascular disease; however, intensely lowering blood sugar is probably not a good idea.

What was reported today at the American College of Cardiology meeting was the blood pressure and cholesterol arms of the study. The blood pressure arm similarly looked at getting the blood pressure to normal (120/80) compared to standard care. Again, both groups had fewer heart attacks and strokes than expected. Thus, blood pressure control is important, just not continuing to add medicines until the BP is normal. The cholesterol arm of the study looked at something different. All the patients were given statins, but half were randomized to fenofibrate, a different kind of cholesterol medicine that doesn't affect bad cholesterol too much (LDL), but does raise good cholesterol (HDL) and lowers fats (triglycerides). Unfortunately, there was no difference in heart attacks or strokes in either group. However, when you looked at diabetics with low HDL and high triglycerides, there was an improvement. In other words, unlike statins which should be given to every diabetic, fibrates should be used only in diabetics with low HDL and high triglycerides. Again, this reinforces the importance of cholesterol lowering in diabetics, despite what the headlines may read.

Bottom Line: If you are a diabetic, try and keep your A1c under 7%, and don't take any more medicines (especially insulin) to try to get the A1c any lower. Blood pressure and cholesterol control are also very important. Diabetics should keep the blood pressure under 130/80, but don't need to keep adding medications to get it perfect (under 120/80). All diabetics should take a statin medications (regardless of LDL number), and if your triglycerides are above 200 and HDL is below 35, add a fibrate to the statin.

Stop Fosamax After Five Years

2010-03-10T18:59:00.000-08:00

There has been a flurry of news about osteoporosis drugs in the media being dangerous. The class of drugs are called bisphosphonates and include medications like Fosamax (now available as generic alendronate), Actonel, and Boniva- the drug pitched by celebrity spokesperson Sally Field. These drugs are designed to treat osteoporosis which is a condition where the bones become brittle. Osteoporosis is common in older women because estrogen, which decreases after menopause, prevents bones from breaking down. In the past, hormone replacement was the primary treatment and preventative agent for osteoporosis, except the Women's Health Initiative study found hormone replacement to be associated with increase cancer and heart attack. Since that study, bisphosphonates have dramatically increased in use. In fact, there is good data to show that bisphosphonates not only strengthen bones, but can prevent fractures. Fractures of the spine and hip can be extremely debilitating.

However, reports from two recent studies surfaced and have created a media storm, and likely significant confusion for the millions of women that take these drugs. Today, the USA Today reported Long-term use of osteoporosis drugs linked to hip breaks and proud ABC boasted in its headlines: FDA to Investigate Possible Osteoporosis Drug-Femur Fracture Link After ABC News Report . This occurred after a Diane Sawyer story about a physician taking a bisphosphonat, who suffered a femoral fracture by doing nothing more than walking. The femur is the long bone in the leg. It is a strong bone, and rarely fractures, unless there is extreme trauma. Thus, it was surprising when reports surfaced of women similar to the doctor Ms. Sawer interviewed having sudden, non-traumatic fractures of their leg bones.

This is not the first we have heard of these reports. In today's FDA statement in response to the media attention (see FDA Drug Safety Communication: Ongoing safety review of oral bisphosphonates and atypical subtrochanteric femur fractures ) the FDA stated:

"Based on published case reports of atypical subtrochanteric femur fractures occurring in women with osteoporosis using bisphosphonates, FDA, in June 2008, requested information from all bisphosphonate drug manufacturers regarding this potential safety signal. All available case reports and clinical trial data were requested. FDA's review of these data did not show an increase in this risk in women using these medications."

In other words, the FDA knew about this, looked at the data, and didn't find a connection. Nonetheless, today's excitement is over two studies presented yesterday at the 2010 Annual Meeting of the American Academy of Orthopaedic Surgeons (AAOS). In one report (here is the link to the actual study ), researchers obtained bone biopsies from 21 postmenopausal women with femoral fractures; nine who did not take a bisphosphonate and twelve who did. They found some differences in the structure of the bone for the women who had taken a bisphosphonate. Of note, the average duration of bisphosphonate therapy in this study was 8.5 years. The second study was done at Columbia University, where researchers evaluated the bone structure of 111 postmenopausal women with primary osteoporosis, 61 of whom had been taking bisphosphonates for a minimum of four years and 50 controls taking calcium and vitamin D supplements. The study found that during the first four years, there was improvement in bone, but after 4 years, the trend started to reverse, and with longer treatment any gains made were diminished.

It is important to point out that femoral fractures are very rare, whereas osteoporotic fractures of the hip and spine are common, which is why bisphosphonate therapy is so important. However, even though the FDA's review in 2008 found no association, it appears there is a least a signal of a potential harmful type of fracture with the use of these drugs. Most importantly, these harmful effects appear to occur only in patients on long term use of these medications. The patient Diane Sawyer interviewed had been on Fosamax for over 10 years. The good news is that the beneficial effects of 5 years woth of taking a bisphosphonate are seen 5 years after stopping! In a study published in JAMA in 2006, Effects of Continuing or Stopping Alendronate After 5 Years of Treatment , patients who had been taking bisphosphonates for 5 years were randomized to taking 5 more years of a bisphosphonate or stopping. Though there were some decreases in bone structure in those patients that stopped the bisphosphonates, there were no differences in hip and spine fractures in the two groups. In other words, for patient taking bisphosphonates, it appears that after 5 years on the drug, at least a 5 year "holiday" should be taken.

Bottom Line: Osteoporotic fractures are a major source of disability for older women in the US. Bisphosphonates are an effective form of treatment for osteoporosis and can prevent fractures. Whether or not bisphosphonates can cause rare femoral fractures is unclear, but if they do, it appears to occur only after long term use. The real benefits of bisphosphonates are seen in the first 5 years of therapy, and experts are now recommending stopping bisphosphonates after 5 years, which should also diminish if not eliminate the risk for femoral fractures. If you are taking a bisphosphonate, don't stop.....unless you have taken it for 5 years or more, in which case you should discuss with your doctor about stopping the medication. (This goes for you too Sally).

Having health insurance doesn't ensure it will be easy to find a doctor

2010-03-09T05:03:00.000-08:00

An excellent article appears in today's Washington Post entitled "Having health insurance doesn't ensure it will be easy to find a doctor," where a young, otherwise healthy and insured woman discusses her extreme difficulty in finding a doctor in Washington, DC who will see her.

"I was just 23, basically healthy and, most important, insured. So I pulled out my computer, looked up the UnitedHealthcare list of pre-approved doctors and started calling. And I got rejected. Again. And again. (Usually after being put on hold for three or four minutes.) "

Next to Massachusetts, D.C. has the largest number of physicians per patients. (The article briefly mentions the lessons Massachusetts has learned about providing health care for everyone without addressing whether there are enough primary care physicians to see them). D.C.'s doctor excess, like Mass., is somewhat exaggerated given that there are several teaching hospitals with more than a few resident physicians. However, there are more than enough docs in D.C. to see patients. The problem is that in addition to not having enough primary care physicians, more and more primary care physicians are not accepting new patients. The article suggests that this is a supply and demand issue, which is true. However, another major factor that the article neglects to mention is that there are many primary care physicians in D.C. gladly accepting new patients. However, they will not take your insurance.

I practice in a large, academic teaching center in D.C. and we stopped taking new patients several years ago. This happened because many of the physicians in D.C. stopped taking insurance, and many of their former patients who were not willing to pay out of pocket to see their former doctor came to our practice (we take virtually every insurance). The problem is that we now have so many patients, they have a very difficult time getting to see us for an appointment.

The article suggests several solutions to increase the number of primary care physicians including recruiting more primary care oriented students into medical school and funding more residency spots for graduates going into primary care. These are good ideas but will not solve the problem. In a survey we did, we found that only 2% of students going into internal medicine were going into primary care internal medicine. The main reason that they chose not to do primary care was lifestyle. Students perceived primary care physicians as too busy, doing too much paperwork, and undervalued by society. Until this problem is fixed, the primary care crisis will remain. ( See Factors Associated with Medical Students' Career Choice Regarding Internal Medicine: Pay is Not Really One of Them! )

I have previously discussed that the same issue happened with psychiatrists years ago, and this is why we have a two types of psychiatry in the US. The psychiatry that you see on the TV and in the movies only occurs for those patients willing to pay out of pocket for their care. Those who pay for mental health with insurance might see a psychiatrist once a year for a few minutes, but any counselling is done by someone else. Getting an appointment with a mental health professional that accepts your insurance is similarly challenging. (See a piece I wrote for KevinMD called "As psychiatry goes, so will primary care," and How can a psychiatrist write 100,000 prescriptions a year, and why this matters to Primary Care? )

Though I believe it is important to support health care reform, it will do nothing to fix the lack of primary care physicians nor does it address the root cause of the problem (see Why you must support health care reform, even though it won't fix our health care system. ). If you are frustrated by the system, one thing to think about is paying out of pocket to see your primary care physician. Though many doctors who see "cash paying" patients run more of boutique or concierge practice, more and more primary care physicians are seeing patients at more reasonable prices, and just desire to get the insurance middle man out of the picture ( see Insurance Free Medicine )

Update: A related post byDr. Toni Brayer was just posted on KevinMd. Primary care needs to be valued first before it can be saved . I think a lot of us are all saying the same thing.

Should all patients with metabolic syndrome or elevated HgA1c take statins?

2010-03-04T18:13:00.000-08:00

Metabolic syndrome is a constellation of factors (increased waist circumference, high blood pressure, elevated fasting glucose, high triglycerides, low hdl) that are associated with increased cardiovascular risk. Metabolic syndrome is often called pre-diabetes both because sugars are high and because metabolic syndrome is related to insulin resistance, the primary mechanism of type 2 diabetes. Diabetes has been generally defined as having a fasting blood sugar of greater than 126, so patients with sugars between 100-125 have also been called pre-diabetics. Like diabetes, we know that metabolic syndrome is associated with increased cardiovascular risk (increased risk for heart attack and stroke). Men with three or more components of metabolic syndrome have more than double the risk for cardiovascular disease, and women with three or more factors have almost six times the risk for cardiovascular disease.

Because diabetes is associated with such a high cardiovascular risk, and because lowering cholesterol with statins in diabetics has proven to reduce these events, current guidelines recommend that virtually all diabetics take a statin, even for those patients with normal cholesterol levels. One question which remains is whether the same should be done for patients with elevated fasting blood sugars and/or metabolic syndrome.

A recent study in the New England Journal called Glycated Hemoglobin, Diabetes, and Cardiovascular Risk in Nondiabetic Adults may give us more reason to consider thinking about using cholesterol lowering agents in patients with elevated blood sugars, even if the cholesterol is normal. The study looked at the relationship of hemoglobin A1c (HbA1c) to development of diabetes and cardiovascular risk. It was not surprising that even high end normal HbA1c's predicted development of diabetes, but what was surprising was that high normal HbA1c was strongly associated with risk for heart attack and stroke.

In the study, patients with an HbA1c of less than 5.0% had 4% relative decreased risk of cardiovascular disease compared to patients with and A1c of 5.0 to 5.5%. However, those with A1c's from 5.5 to 6.0% had a 23% increase, those with A1cs of 6.0 to 6.5% had a 78% increased risk, and those with 6.5% or greater had an almost double risk of cardiovascular disease. This suggest a strong correlation between elevated blood sugar (pre-diabetic patients) and cardiovascular risk.

In the most recent updates to the ADA guidlines published in the January 2010 edition of Diabetes Care, the ADA now defines diabetes as patients with an A1c of >6.5%, and those patients with A1c's between 5.7–6.4% have been included in a category of increased risk for future diabetes. Thus, the last group in the recent study would now be considered to already have diabetes.

This study also made me think of the JUPITER trial. The JUPITER trial is a controversial trial which I have blogged about before (see Jupiter is Out, and the News is Good! and Crestor: Get Ready to Ask Your Doctor for the CRP Test). It showed that patients with relatively normal cholesterol levels, but high levels of CRP benefited from taking 20mg of Crestor. Crestor now has an FDA indication for primary prevention of heart disease.

Interestingly in the JUPITER study, 41% of patients had the metabolic syndrome. The median A1c was 5.7 (interquartile range was 5.4-5.9). This means that about half the patients in the study had an extra 23% increase for cardiovascular disease based on A1c alone, and about 25% of patients had a 78% additional risk or higher (with the new ADA definition, there was probably not an insignificant number of patients in the JUPITER study that had an A1c above 6.5% that would now be considered to be diabetic and should have been on a statin). The reason I bring up JUPITER is because we now have a primary prevention trial in which a substantial number of patients had metabolic syndrome or elevated sugar, and this trial showed that statins were beneficial.

Thus, there are compelling arguments that can be made to suggest that patients with either metabolic syndrome or an elevated HgA1c should be on a statin (similar to diabetics) regardless of their cholesterol number.

However........
1. In order to definitively make this case, you would need a large, randomized clinical trial of patients with metabolic syndrome (or A1c's between 5.5 and 6.5) and normal cholesterol, randomized to statin or no statin. I am hopeful that the NIH or some drug company is planning on doing this.
2. In a subgroup analysis of the JUPITER trial, the investigators looked to see whether metabolic syndrome was a factor in those patients that benefited from Crestor and didn't find a statistically significant difference. It appears that CRP levels and not sugar levels is what made the difference.
3. Though the presence of metabolic syndrome does predict cardiovascular disease, it predicts diabetes much better, and the Framingham risk score is a much better predictor of cardiovascular disease (see Metabolic Syndrome vs Framingham Risk Score for Prediction of Coronary Heart Disease, Stroke, and Type 2 Diabetes Mellitus )

Bottom Line: Elevated HgA1c levels and metabolic syndrome substantially increase risk for cardiovascular disease, and there are compelling reasons to consider statin therapy in these patients, though conclusive data is lacking. As per the new ADA guidelines, patients at risk for diabetes should be screened with a HgA1c, and if it is greater than 6.5%, these patients are now considered diabetic and should receive a statin.

Since the Framingham risk calculation is still the best predictor for cardiovascular risk, a reasonable approach might be to adjust the Framingham score for patients with HgA1c's between 5.5% and 6.5%. Currently, patients with a Framingham risk of greater than 10% are considered for more aggressive LDL goals (which usually means they need a statin). Based on the numbers from the recent New England Journal study, for patients with A1c's from 5.5 to 6.0%, more aggressive goals should be considered when these patients have a Framingham score of 8% (instead of 10%), and for those with A1cs of 6.0 to 6.5%, more aggressive goals should be considered for a Framingham score above 6%.

Why Barack Obama should come clean about his smoking and what he can do to quit

2010-03-02T06:02:00.000-08:00

As a physician I believe that your personal health should be private. I can certainly understand why the American people would want the right to know about a potential presidential candidate's health prior to an election. However, afterwards, the health of a President, unless life threatening should probably remain private. That said, the President recently had a complete physical and the results of that physical are now public. In addition to knowing the President's blood pressure and cholesterol numbers, we now also know according to a New York Time's report (President in ‘Excellent Health,’ Routine Checkup Finds) that President Barack Obama continues to smoke. Though I still believe that health should be a private matter for patients, even if that patient happens to be the President, since our President has chosen to reveal his health information, I think that he should officially come clean about how much he smokes. According to the New York Times report, all we know is that he doesn't smoke on a daily basis, but rather smokes infrequently. In June, the President was quoted as saying, “Have I fallen off the wagon sometimes? Yes. Am I a daily smoker, a constant smoker? No.”

Tobacco smoke in the US is an important matter. It is currently the single leading cause of preventable death and accounts for billions of dollars in health care costs. Given our current health care crisis, including the escalating costs of health care, I think it would be important for the President to discuss the burden of tobacco in this country as well as his own struggle in quitting cigarette smoking.

Now as far as what the President can do, a lot depends on how much he smokes. My guess is that he probably smokes a few cigarettes a few days a week during stressful times. If this is the case, then withdrawal is likely a minimal concern, and his nicotine consumption is probably just reinforcing this very bad habit. If that is the case, stress management techniques are probably the best way to quit. I advise patients who smoke only a few cigarettes a day to think about what else they can do to manage their stress besides smoking. For example, taking a walk, reading a book, meditation, prayer, etc. Something that is relaxing and reduces stress. Certainly our President is under a lot of stress and one can understand why he would need some sort of stress relieving activity. Smoking cigarettes is obviously not the best way to reduce stress.

If the President does smoke more than just a few cigarettes a day, the current guidelines recommend that most patients benefit from pharmacotherapy (medication). Nicotine replacement in the form of lozenges, gum or the patch have been effective in doubling quit rates. Even more effective than nicotine replacement are pills, specifically buproprion or Chantix (Varenicline). Recently there's been some concern about safety issues regarding Chantix, ( see More FDA warnings should not be cause for worry. and Where's the Good News about Chantix? ) initially brought up by the FDA. However, these safety concerns have not seemed to have panned out, and more recent studies seem to indicate that Chantix is very safe given certain precautions, specifically worsening of mental conditions. Patients using any form of a medication should be aware that quitting cigarettes (with or without medication) can worsen underlying mental health conditions, such as depression or anxiety.

In addition, I have blogged previously about Electronic Cigarettes , which I have received a number of comments (also see More on Electronic Cigarettes or E-cigs ). I think those who responded are mostly e-cigarette users that have misunderstood my objections to e-cigarettes. My objection is not that I am opposed to the existence of electronic cigarette. It's more that e-cigarettes are not regulated, so 1) their safety cannot be completely ascertained and 2) they are being promoted as a smoking cessation treatment, which they have not proven to do. E-cigarettes are likely a healthier alternative to tobacco smoke, but should be regulated by the FDA since they do contain nicotine. I'm also bothered that electronic cigarettes are sold in our shopping malls, and can potentially be purchased by children. Electronic cigarettes are probably less carcinogenic, than tobacco cigarettes. However, nicotine itself has unhealthy effects, and the goal of smoking cessation should be getting off nicotine completely. All of the treatments for smoking cessation such as the patch and the gum and even the pills are only supposed to be used for short periods of time, usually three months to no more than 6 months. Electronic cigarettes might be safer replacement for tobacco cigarettes, but are not designed to get patients off of nicotine. Generally, most of the nicotine replacement products work by giving patients a continuous supply of nicotine, and eventually weaning that level down once the patient has been off tobacco cigarettes for a few weeks. For example, with the nicotine gum or lozenge, you don't take a piece of gum every time you crave a cigarette. Rather, you use the gum continuously throughout the day, starting with about 15 pieces per day eventually decreasing the number. Theoretically, the electronic cigarette could be used in that manner, but by just replacing a tobacco cigarette, you are not addressing the behavioral issues related to smoking cessation. So, while I believe that electronic cigarettes may be safe, I also believe they should be regulated by the FDA and should not (until proven) be used or promoted as smoking cessation agents.

The President could also call 1-800 QUIT NOW. This is a 24/7 support line designed to help patients quit tobacco products. It is free and fully funded by money from this tobacco settlements. This program can be used use in conjunction with treatment from your health care provider as well as with medication, nicotine replacement and other smoking cessation techniques.

Bottom Line: While I do believe the President's health is a personal matter, since he has come out admitting that he is still smoking cigarettes despite his promises to our First Lady, I believe that he should admit to exactly how much he still smokes as well as further discuss his own personal struggles with his addiction. This will hopeful bring additional attention to the problem of cigarette smoking, which remains the single leading cause of preventable death in our country.

Why you must support health care reform, even though it won't fix our health care system.

2010-02-25T18:08:00.000-08:00

There are certain actions we take even though we know that ultimately we will not be successful. Sometimes we do this out of hope for a better tomorrow (like playing the lottery) or because we are taking a moral/ethical stand (like supporting a candidate that has no chance of winning). Supporting health care reform is probably a little of both. Even if any of the currently proposed health care reform plans pass, it will make little impact on our crumbling health care system. That said, you MUST support health care reform now. By support, I mean contacting your representatives, telling your friends/family, etc. (feel free to share a link to this post).

Why we have to support health care reform now:
1. The current system is worse then broken. You probably know about the over 40 million Americans that lack health care coverage, and the fact that we pay more than any other country for health care, but have poorer health than most other countries. However, non-health related facts may be even more important. The most common reason for bankruptcy in the US is medical bills. In addition, our nation's industries can not compete in a global market because of health care costs. GM spends more on health care for its employees then the metal in the cars they make. The health care system is not only broken, it is crippling our entire company.
2. If we don't act now, reform may never happen. Congress goes into recess at the end of the month. By mid-April, our representatives will start to focus on the mid-term elections. Thus, it is likely that nothing substantial will get done this spring, summer and fall until after November, 2010. If this is the case, regardless of the outcomes of the upcoming elections, no politician will want to tackle health care any time soon.
3. We are so close. We have never before had health care bills that have been passed in both the House and Senate. This is historic. We can't stop now, because we may never get this close again.
4. There are actually some good things that will happen if reform is passed. Even if we don't cover all the uninsured, any bill that covers millions more has to be worthwhile. Both side also seen to agree on eliminating pre-existing conditions and closing the Medicare Part D donut hole will be a major help to many of our seniors.

Why the current health care reform proposals won't work
1. Coverage is not enough. There are four major problems with our current health care system: lack of coverage (uninsured, underinsured, pre-existing conditions), escalating health care costs, a poor delivery system including a primary care shortage, and an unhealthy population. The other issue, of course, is how to pay for any fixes. Current proposals pay lip service to all four, but really only address coverage. All are inter-related, so without addressing the others, your can't fix the system. Massachusetts is a perfect example. After expanding coverage to all residents, the state found that there weren't enough primary care doctors to see everyone. These newly insured patients ended up going to the ER, leading to dramatically increased costs for the state. I believe we should have first addressed rising costs and our delivery system. Fixes include malpractice reform and restructuring our payment system which pays for tests and procedures over prevention and counselling.
2. You are probably not affected. If you are reading this, you are doing so a work (you have a job) or at home (you probably have a job if you can afford shelter with a computer and Internet connection). This means that you likely have health insurance that is provided by your employer, like most Americans between 21-65. Similarly, you are likely not happy about your escalating health insurance premiums and possibly frustrated by longer and longer waits for shorter and shorter appointments with your doctor. However, you likely want to keep your doctor, are thankful you have coverage, and though you feel bad for the uninsured, you are more fearful of what substantial reform might mean for you. The good news is that whatever passes will likely not affect you. The bad news is that we will likely not get any real change until things get so bad that most Americans demand change.
3. Things are bound to get worse. Though our dysfunctional system and plans for reform may not affect you now, things will get worse. Without addressing costs, premiums will continue to go up and even more patients will lack the ability to afford health care coverage. Without addressing the bureaucracy of insurance paperwork and they pay disparity between specialists and primary care physicians, students will continue to go into non-primary care fields and current primary care doctors will retire. In addition, our nation is only getting older and fatter, and thus sicker and more expensive.

Bottom Line: Our health care system needs massive changes. This can't be done quickly, so one piece of legislation will not fix it. It will take many years and many pieces of legislation just to start moving in the right direction. However, we have to start somewhere. Though the current proposals will not work, they are a first step. In addition, a millions of Americans will get coverage and we may get a few needed fixes. Yet, if we fail to take this first step, and don't pass something soon, it may be a decade before health care reform is discussed again.

More Avandia Scare- Again, Unwarranted.

2010-02-21T09:04:00.001-08:00

Here we go again......

A piece recently published in the New York Times and cited by others has just kicked up the Avandia controversy again. As usual, this is both unnecessary, and will likely scare patients and cause more harm than it is trying to prevent. (In many ways like the current LABA scare).

I have blogged extensively on Avandia safety.
The Avandia Scare: Why it Matters, Who's Responsible, and What to Do ,For the RECORD, Avandia does not cause heart attacks, Avandia Vindicated, and The Diabetes Conspiracy.

Before going diving into what the hubub is about it is important to note two extremely important facts:

1. There is no new data or information here. Everything being discussed is old news.

2. The one thing NOT being discussed in all these reports is that the question of Avandia safety was answered this past July at the American Diabetes Association's annual meeting when the RECORD trial was presented which definitively showed that Avandia did not cause heart hospitalizations, cardiac deaths, or any heart problems.

What's this all about?

The New York Times got a hold of a report that is now public from Senators Grassley and Baucus. What is available is the Press release and the full report of their two year investigation into the FDA and GSK's handling of Avandia safety. Their letter to the FDA states that GSK knew that that there were cardiac risks associated with Avandia and did not make these risks known to the public or the FDA soon enough. The second charge they make is that the study the FDA has requested GSK conduct to test safety differences between their product Avandia and their competitor's (Takeda) product Actos called the TIDE study is unethical, because two FDA safety officers felt that since there was no benefit of Avandia over Actos, and that Avandia had heart concerns that Actos did not, the study would needlessly harm patients. One of those safety officers was Dr. David Graham.

The full report is a 342 page document that includes publications, FDA data and internal communications at GSK. One of the main focuses of their concern is that the RECORD trial was continuing when GSK knew that the initial heart attack rates were low, so low in fact that it was unlikely that when finished, the RECORD trial would have enough events (statistical power) to show whether or not Avandia was safe. What is not highlighted in the report (which comes out 6 months after RECORD was presented) is that RECORD actually did meet criteria for statistical power. In other words, all their worry was for naught. Another focus of the report was study 211, which as a study on using Avandia in patients with heart failure. (More on that later).

You can argue whether or not the Senators have a point regarding what the FDA and GSK should have done and by when; however, from a clinical perspective there is nothing new in this report. More importantly, it was irresponsible of them not to discuss the final results of RECORD in this context.

Study 211
Study 211 was actually published in the well respsected Journal of the American College of Cardiology. It showed that when giving Avandia to patients with class 1 and 2 heart failure (a relative contraindication) that Avandia did not statisctically increase the rates of heart failure, death or heart attack. The only differences seen were more edema (a known side effect of Avandia, especially for patients with heart failure) and more need for medications. The essential findings of the study is that Avandia increases fluid retention (we know this, Actos does this as well) but does not actually have any effects on the heart. Why the senators want to make a big deal of study 211 is beyond me. If anything it shows that even in patients who you shouldn't give the drug to, there were no real problems.

What about the recommendation to take Actos instead of Avandia?

This is probably the scariest and most harmful outcome of the report and the media attention surrounding it. Every media outlet has not publisehd the following quote: "if every diabetic now taking Avandia were instead given a similar pill named Actos, about 500 heart attacks and 300 cases of heart failure would be averted every month because Avandia can hurt the heart"

This statistic comes from a letter written by Dr. David Graham to the FDA expressing concerns about Avandia over Actos. What Dr. Graham did is compared two Avandia meta-analysis with one meta-analysis on Actos. The two Avandia analysis used were Nissen's and the Singh meta-analysis published in JAMA. The Singh meta-analysis looked at ADOPT, RECORD and DREAM (which the FDA did a meta-analysis on and showed NO PROBLEMS with Avandia), and added study 211, which is a focus of the Grassley report. As mentioned, study 211 was a study done in 200 patients with heart failure, and since we know that Avandia does in fact increase the risk of heart failure, the patients in this study are not ones that you would normally give Avandia. Nonetheless, the Singh meta-analysis, unlike the FDA's, showed problems with Avandia, consistent with Nissen. ADPOT, DREAM and RECORD had thousands of patients. Study 211 had only 200. In other words, the only reason the Singh meta-analysis was positive and the FDA's was negative is that Dr. Singh added the 200 patients from study 211.

The Actos meta-analysis was published in JAMA, and found no heart attacks with Actos. One needs to note that one of the authors on the Actos meta-analysis is Dr. Nissen. Also, one should note that Takeda, the makers of Actos, gave Dr. Nissen and colleagues $25,000 in funding. In other words, Dr. Nissen has two published meta-analyses, one that is not funded that finds heart attacks in Avandia, and one funded by the makers of Actos that finds no heart attacks in Actos. As Arsenio Hall used to say, this is something that makes you go "hmmmmmmm."

Dr. Graham's conclusion is that comparing the Actos and Avandia meta-analyses, there were excess heart attacks and heart failures in Avandia over Actos, so that for every 63 patients taking Avandia instead of Actos for 1 year, there would be an additional heart attack. He then looked at the number of patients taking Avandia and came up with the 500/300 cases.

In addition to jumping to major conclusions from meta-analyses, one of the bigger problems here is comparing results from separate studies. This is breaking a cardinal rule of evidence based medicine. Doctors should be familiar with this because drug company reps do this all the time. They say, "my drug's studies show that my drug does X and my competitor's studies only show that their drug does Y, so you should use my drug." The astute clinician should politely ask the drug rep about head to head studies. Most often, the response will be that there are none. It is critical when making comparisons between to therapies, that head to head studies are done. Unfortunately, head to head comparisons are often not done by the drug companies because there is a huge financial risk if the results show that your company's drug is inferior. This is why proposed legistlation is rightfully calling for funding of comparative effectiveness research. In other words, Dr. Graham is stating that Actos is safer then Avandia WHEN THERE ARE NO HEAD TO HEAD STUDIES COMPARING THE SAFETY OF BOTH DRUGS. Unfortunately, this incorrect and inflammatory statement is what gets picked up by all the media. To be clear, I don't believe that Actos is harmful. I think both drugs are safe, though they both show similar side effects (fluid retention, edema and osteoporosis) and should be used with caution in certain patients (HCF).

A Diabetes Conspiracy?

This report if anything give more credibility to my postulations.
- It was Grassely and Baucus that called for congressional hearings back in May 2007, the day of the Nissen publication was announced. It was as if they new about the controversy before the story broke. The fact that they continue to draw attention to this issue (and themselves) despite the fact that the issue has been scientifically resolved and that health care reform is on life support is a concern.
- We again hear the name of Dr. David Graham, the FDA insider on Vioxx. I contend that somehow Nissen was tipped off from someone inside the FDA to publish the Avandia data himself, since the FDA decided to keep this data from the public. After this report, Graham continues to be my likely suspect. Regardless, if anything should be looked into, it should be whether or not classified FDA documents or conversations were leaked to Dr. Nissen. I am not a lawyer, but I think this is illegal.

Bottom Line
1. Nothing new here. Avandia does not cause heart attacks, as proven by the RECORD trial.
2. Quote on Actos safety over Avandia is based on no truly comparative (head to head) studies, and thus should not bebelieved, especially given #1.
3. Don't the Senators have other things to worry about....like fixing health care?

4. Someone should take a closer look at how Nissen "discovered' the link between Avandia and heart attacks. This is the congressional hearing I would like to see.

FDA Blows it on LABA Safety

2010-02-18T17:56:00.000-08:00

The FDA just killed a few asthmatics!

I have blogged extensively regarding LABA safety (see The Lowdown on LABA's , Good News for Asthma Patients , Asthma Medication: Calling Out the Safey Advocates and Dear FDA, Remove the Boxed Warning from Advair and Symbicort )

As reported today in the Wall Street Journal and MSNBC (so far), the FDA announced today that is was changing the labelling on products containing long acting beta2 agonists, or LABA's. One of the changes was recommending that "LABAs should be used for the shortest duration of time required to achieve control of asthma symptoms and discontinued, if possible, once asthma control is achieved."

Not only did the FDA get it wrong regarding their interpretation of the data, but they did two surprising things. First, in addition to simply saying what is safe and what is not (their job), they made treatment recommendations (not their job); recommedations that are actually not consistent with national guidelines. Secondly, their recommendations are based on absolutely no data! In fact, the limited data available would suggest that their approach may not be a good idea. Finally, taken together with the fact some of the headlines will scare patients and cause them to simply stop taking their medications, patient will undoubtedbly suffer. Ironically, the FDA's reaction to the few potential harmful effects that they are worried about regarding LABA's have led to actions that will likely cause substantially more harm to patients.

LABA's ARE SAFE WHEN TAKEN WITH INHALED STEROIDS

At face value, the LABA safety issue should not be an issue. Asthma deaths climbed steadily into the mid 90's, unlit about 1996/1997 when the rate of asthma deaths declined for the next decade and have remained stable over the past few years at about 4000 death per year. LABA's were introduced at exactly the time that asthma deaths declined. Though one can not prove that the decline in asthma death rates are due to the use of LABA's, it certainly can not be the case that LABA's cause asthma deaths.

One of the FDA"s recommendations did make sense: LABA's should not be taken alone and only used with an inhaled corticosteroid or ICS. The entire LABA controversy centers around the SMART study published back in 2006. SMART was a very large (over 23,00 patients) study done by GSK, the makers of the LABA salmeterol, looking at its safety. The problem was that it didn't study only asthmatics taking ICS, but asthmatics taking any medication. The study was stopped early because certain subsets of patients, particularly African Americans, seemed to have increased risk, including asthma death. Because of these findings, the FDA not only applied a boxed warning to salmeterol, but all LABAs and products containing LABAs. Advair, one of the most common asthma controller medications contains the LABA salmeterol and an ICS. The data from the SMART study was very clear that most of the problems came from asthmatics taking LABA's alone, and that there were no increased problems (regardless of ethnicity) when using a LABA with and ICS. In fact, no one taking Advair or Symbicort equivalents in the SMART study died! However, this was not enough for the FDA or critics to give ICS plus LABA products a pass on the boxed warning. The only way to prove to the FDA (and some critics) that ICS + LABA's are safe would be to do another SMART like trial on patients taking ICS alone or ICS+LABA. The problem is that this trial would likely require at least 250,000 patients (because events are so rare), and no drug company is going to fund that study. In an effort to get more data, several meta-analysis were done. GSK's own meta-analysis which looked at ICS + salmeterol compared to ICS alone showed that ICS + LABA actually decreases the risk for severe exacerbations, and did not increase the risk for asthma-related hospitalizations or asthma-related deaths. The FDA did their own meta-analysis (most of the data coming from SMART) which seemed to show the same thing. In fact, regarding Advair, the committee voted 27 to 0 that Advair was safe. Thus, it is quite surprising that the FDA would go in a different direction that what their advisor committee was suggesting.

THE FDA'S RECOMMENDATIONS TO STEP DOWN TO ICS AFTER CONTROLLED ON ICS + LABA ARE NOT EVIDENCE BASED OR CONSISTENT WITH NATIONAL GUIDELINES

The most recent asthma guidelines were published in November 2007. There is a strong focus on asthma control. The guidelines say that the focus of asthma care should be control, and that if control is not achieved, therapy must be stepped up, because poorly controlled asthma puts patients at risk for bad outcomes, such as hospitalization and death. In a recent study, we showed that that majority of patients in the primary care setting had poorly controlled asthma, and that one out of every three patients seen in primary care was using a rescue albuterol inhaler every day. The guidelines suggest that once asthma control is achieved that providers can continue therapy or CONSIDER stepping down. The guidelines are very specific that step down therapy should be done carefully, as it might risk worsening asthma. In addition, when talking about step down therapy, most of the discussion in the guidelines is about reducing the dose of the ICS, and not discontinuing the LABA (supported by data published in the New England Journal) Thus, by mandating that patients who are well controlled on ICS+LABA step down to an ICS alone, the FDA is both dictating treatment, which is not really their role, and in doing so, going against well accepted guidelines developed by an expert panel from the NIH! More importantly, there is extremely limited data on which route is best in a stable asthmatic patient: continuing ICS + LABA or stepping down to ICS alone. One study in the US of 647 patients controlled on Advair did worse when stepped down to ICS alone. Another French study of 467 asthmatics studied over 6 months showed that stepping down to a lower dose of Advair was fine, but stepping down to ICS alone (what the FDA recommends) caused problems. There are only a couple more studies like this done, all showing the same thing: the FDA's recommendations are ill advised.

PATIENTS WILL STOP THEIR ADVAIR, AND THIS WILL LEAD TO EXACERBATIONS

There is very compelling data that shows when asthmatics stop their controller medications, that bad things happen, including ER visits, hospitalizations, and even death. First, though data is limited, there are studies which suggest that patients taking ICS + LABA are more likely to refill their prescriptions than those taking ICS inhalers alone. In fact, in one managed care study, the adherence to ICS + LABA in one inhaler (i.e Advair) was double that of patients taking the ICS alone. In addition, prescriptions for the rescue medication albuterol, as sign of worsening asthma, was higher in those patients taking an ICS alone. Thus, it is possible that patients who step down from and ICS + LABA to an ICS alone may not be as adherent to their controller asthma medication, and could get sicker. Finally, many physicians will attest to the fact that when there is bad press about a medicine, patients will stop, sometimes without discussing it with their doctor. We looked at patients in our practice after the Avandia scare in 2007, and found that many stopped taking the medication without discussing this with one of our physicians. Anecdotally, when the SMART data was first released and drew media attention, several physicians from various parts of the country told me they noticed increased ER visits due to asthma. This is why I am certain that the FDA decision today will cause patient harm.

What every medicine cabinet needs

2010-02-17T18:22:00.000-08:00

Here in D.C., we are slowly starting to thaw from what my friends on Facebook have been calling "snowmageddon" or the "snowpocolypse." We haven't had this much snow in DC for over 100 years!
Today's Washington Post had an interesting article entitled "What Every Medicine Cabinet Needs." Because traffic around the Beltway is normally horrible, we in the DC Metro area run to raid the local grocery store at the first sign of snow. However, a stop at the pharmacy isn't usually considered since it generally doesn't snow that much here. However, this latest winter blast found many stuck in their houses for days, unable to get to a store or pharmacy. Some pharmacies shut down. All of this leading to the Post's question in preparation for the next blizzard. They asked a few local docs and here's what they came up with:
Neosporin
Bandages
Hydrogen peroxide
Benadryl
Tylenol
Aspirin
Thermometer
Robitussin
Neti Pot
Vicks VapoRub
Plan B

While I think the list is a good start, I might change or get rid of some and add a few. Here's my list.
Neosporin and Bandages- both useful in case of cuts and scrapes
Rubbing alcohol -prefer this over hydrogen peroxide, but either probably OK
Benadryl - a life saver in case of a severe allergic reaction. Also, before Ambien, this is what we used for insomnia.
Tylenol-good for fever, headache
Naproxen (Alleve)- though also good for fever and pain, slightly better than Tylenol for menstrual cramps and muscle pain (that one might get from shovelling 2 feet of snow). Also, for high fevers, you can take both naproxen and Tylenol. Aspirin is not a great pain reliever because at true anti-inflammatory doses, it can cause side effects, which is why it's not on my list. Though aspirin can prevent heart attacks, if you are at high risk (diabetes, high blood pressure) you should be on a baby aspirin every day, and this would be part of your regular meds and not something in the back of the cabinet.
Decongestant- I would ditch the Robitussin and Vaporub from the Post's list. These do absolutely nothing. Neti pots are OK for allergies, but unless you are a regular user, no need to keep one around. If you get a cold or congestion, or even a cough which is usually caused by post nasal drip and congestion, decongestants work great. If you can, get the pseudoephredrine that's behind the counter.
Dextromethorphan. Robitussin or guaifenessin doesn't do much, but dextromethorphan which is the DM in Robitussin DM works great on coughs. Delsym is DM strait up and tastes good too!
Antacids- Tums are OK, but now that Prilosec is OTC, I would have some of these on hand. That frozen pizza you are stuck eating during a snowstorm could cause bad heartburn.
Laxatives- constipation can be quite uncomfortable. Though increased fluids and high fiber foods might help, it's always good to have a laxative on hand. My preference is Miralax.
Hydrocortisone cream 1%-eczema is common in the winter, and lots of things can irritate the skin, which a cortisone cream will fix.

Statins Don't Cause Diabetes

2010-02-17T06:06:00.000-08:00

As of this morning, the only major source reporting the results of a recent study from Lancet is Business Week. However, the headlines that will likely pop up in the next few hours will likely be similar to theirs: "Cholesterol-Cutting Drugs Raise Diabetes Risk by 9% in Study." In my last post I discussed how the media likes bad news stories, so even though this is not yet all over the headlines, I will take a preemptive strike for potentially concerned patients.
The Lancet study is a large major meta-analysis of major statin trials, looking to see if there is a risk associated with statins and the development of diabetes.

The authors likely got the idea to do a meta-analysis from the JUPITER trial which showed that Crestor reduced heart attacks in patients who wouldn't have generally gotten a statin, except they had an elevated CRP (see Crestor: Get Ready to Ask Your Doctor for the CRP Test. ) One thing seen in this study was a potential increased risk of the development of diabetes. I mentioned this in my blog post when the data was first released that physician report of diabetes was increased in the Crestor group (270 reports of diabetes, vs. 216 in the placebo group; P=0.01). I stated that though one might be concerned about this, these were physician reports without confirmation. When looking at the study lab values in Jupiter, there were no significant differences with respect to the fasting blood glucose level, and the A1c level was pretty much the same (5.9% and 5.8%). I also mentioned that there was no biologically plausible reason to suspect Crestor, or any statin, as a cause of diabetes. In addition, both groups of patients in the JUPITER study had a 41% prevalence of metabolic syndrome, which is a pre-diabetic state. Therefore it should not have been surprising to find an increase in diabetes in both groups.

The meta-analysis looked at Jupiter and several other studies combined and found a 9% increase in the development of diabetes in patients taking statins.
So if this is true, how can you say that statins don't cause diabetes????
1. The 9% value is a relative risk, not an absolute risk. If 1/100 patients taking placebo have a side effect, and 2/100 patients taking a statin have a side effect, the relative risk increase is a doubling or 100%, but the real or absolute risk is only 1%. Drug companies and the media (and unfortunately some authors, as was the case in this study) like to talk about relative risk instead of absolute risk, because it makes there drug/data/news story look better. In this study, the actual increase in diabetes was 0.38% or about one third of 1%. Even though the result is statistically significant (true by scientific standards), the magnitude of the increase is so small that there is a high possibility that this is not true.
2. The study is a meta-analysis, which by design can not prove causation. The only way to really find this out is to do a large, randomized controlled study to specifically look at whether or not statins cause diabetes. This will never happen because 1) given the low absolute risk, the number of patients needed in this study would be tens to hundreds of thousands, which means the study would be ridiculously expensive and 2) with Lipitor going generic, no drug company is going to fund such a study. I spoke of the dangers of meta-analysis many times, specifically in talking about Nissen's meta-analysis of Avandia (multiple posts on this). Even in Nissen's own meta-analysis showing a "40% increase in heart attacks" in patients taking Avandia (relative risk), there was really NO DIFFERENCE in the absolute risk in his study! Of course that didn't stop the press, and millions of patients stopped taking Avandia. Unlike the randomized, controlled trial for statins and diabetes we will never see, there was a randomized controlled trial on cardiac safety and Avandia called the RECORD trial which was presented at the ADA this past summer. It showed NO RISK of heart attacks with Avandia. Don't be surprised if you never hear about this, since the press does not seem to be too fond of reporting good news.
3. As above, there is no biologic reason to believe that a statin medication would cause diabetes.

In other words, what you are seeing in the headlines is statistical garbage, that really doesn't mean anything. An incredibly low absolute risk found in a meta-analysis without a biologic reason to support a connection between statins and diabetes should not be cause for concern.

Lipitor: Responding to Space Doc

2010-02-16T17:43:00.000-08:00

I have now been blogging for over two years, and it has been quite an adventure. One of the best parts of blogging has been comments and communications from readers. Granted, the negative comments do take some getting used to, as the anonymity of the Internet allows some posters (though thankfully very few) to be somewhat blunt and in some cases rude. (I publish all comments that are not trying to sell something). However, the vast majority of comments and communications from readers, even when they disagree with my opinions, have been interesting and extremely rewarding for me; especially when it comes from a patient who feels like they were helped from one of my posts.

I received a recent email from a reader on my recent post Bad cholesterol not that bad? Shame on MSNBC...Again! That emailer suggested that I check out the work of SpaceDoc and cc'd him on the email. I subsequently received an email response from SpaceDoc himself. (I have posted his entire email below for fair balance). Rather then respond directly, I thought I would respond in a follow up blog post.

I actually became familiar with SpaceDoc when a close friend told me about her mother who had sudden memory loss with Lipitor. The doctor's web site www.spacedoc.net was Google's first hit. Spacedoc is really Dr. Duane Graveline, MD, MPH, a family physician who started is career as a US Air Force Flight Surgeon , and then went to NASA serving as a flight controller for the Mercury and Gemini program and was selected as one of NASA's six Scientist Astronauts in 1965. He then practiced many years as a community physician before retiring. However, Dr. Graveline is probably better known for raising awareness of side effects from statins. He wrote his first book "Lipitor, Thief of Memory" after having two episodes of something called transient global amnesia (TGA) which he states was associated with his use of Lipitor from 1999 - 2000. (A condition that was clearly the same as what my friend's mom had).

As a seasoned family physician and NASA scientist, I do not doubt Dr. Graveline's sincerity or integrity. Though I have not read the entirety of his work or reports, I do not question their veracity. Where I think we may differ is perspective. As someone who has now suffered several side effects from a statin medication like Lipitor, Dr. Graveline has personal reasons to be concerned, and why he now spends a significant amount of time looking into side effects of statins. However, in my experience I have prescribed thousands of statin prescriptions, and not seen these side effects. On the contrary, I have seen patients at very high risk for heart attacks and strokes live event free due to cholesterol levels at NIH goals. Furthermore, I worry about patients who are at risk and not at their cholesterol goals, particularly those patients who refuse to take statins because they worry about side effects.

As stated in my previous posts (and others), there are simply no medications that are completely safe. Aspirin and now Tylenol might never be approved by the FDA if they were submitted as new drugs today. In addition, in my opinion, any medication can cause any side effect in any individual patient. I never dismiss a patient who relates a certain side effect to a new prescription, though I will tell them whether their possible side effect is a known common, known rare or unknown side effect.

In my opinion, medications are all about risk/benefit ratio. And when it comes to statins, I have a really hard time coming up with a medication class that has a better risk/benefit ratio then a statin (please post a comment if you can come up with a drug with a better risk/benefit ratio then a statin).

Depending on the study you look at and how risky the populations statins reduce heart attack/stroke by about 5-10% (that's absolute risk, you would need to treat 10-50 patients for a few years to prevent 1 event) and reduce death by about 1% (need to treat 100 patients with a statin to prevent 1 death). The most common side effect is myalgia or muscle pain, which about 3% of patients will get, but this pain is usually mild and usually goes away. The rare and serious side effect that the TV advertisements warn of that could be related to muscle pain is called rhabdomyolysis. It is pretty rare (about 1 in a million), but is serious and 10% of patients who get this can die. However, using the FDA data that Spacedoc cites (below), from October 2003-2004, the rate of rhabdo was about 1/500,000 (not including Crestor). During that year there were 120 million statin prescriptions written. Given data that shows that patients on average fill their statin prescriptions 50% of the time (6/12 prescriptions per year), that would give a rough estimate of about 20 million patients on statins during that year (number is probably much higher). Using these numbers, with 20 million patients taking a statin, you are preventing at a minimum of 400,000 heart attacks and strokes and 200,000 deaths, but 40 people will get rhabdomyolysis and 4 of them will die from this. Even if you add up all the other rare and serious side effects mentioned by Spacedoc and others to the rhabdo events, the positive outcomes of statins are favored at least a thousand fold. These are great odds in my mind.

Research into adverse events is very important. One bad event is one too many. If we can figure out why some of these rare side effects occur, maybe we can prevent them in patients at particular risk. However, the media and blogsphere tends to focus on bad news. This news sometimes needlessly scares patients. One of my patients has high cholesterol, poorly controlled blood pressure, and has already had her first stroke. Yet, she is petrified of taking a statin because of everything she has "read and heard." This is why I am so concerned about articles like that mentioned in Men's Health and regurgitated on MSNBC. When it comes to medical journalism these days, there seems to be a major lack of balance. This leads to patients stopping or not taking medicines that can help them, and this will unfortunately lead to preventable heart attacks, strokes and death.

Email from Spacedoc:

Mathew,when you respond that statins are extremely safe and transient global amnesia is extremely rare I wonder how familar you are with the true spectrum of statin side effects. On the subject of TGA, do you know that over 1,000 cases of TGA have been reported to Medwatch over the time period 1998 to present and none of this as been reported to the medical commnity? Don't you wonder about this? And do you know that our thousands of of peripheral neuropathy cases are permanent? And of our tens of thousands of cases of myopathy, 68% will be permanent? And how about our over five hundred cases of disabling ALS-like neuromuscular degeneration (I happen to be disabled with this one but after three years of supplements I seem to be getting better. I still use a walker, however. That's why John Edwards MD of WHO called this "ALS-like" - different pathways and mechanisms may be involved). FYI about Medwatch not reporting I have attached my paper (with Jay Cohen MD as Co) done several years ago when our Medwatch count was 662 just for Lipitor. and remember this was just for amnesia not for the other lesser forms of cognitive deficit such as disorientation, confusion, forgetfulness, dementia and short term TGA measured in minutes not hours. Additionally I have copied you on my survey of other Medwatch data from the same CD that I took my cognitive data. And read this link below for an assessment of where I am right now on my statin research. It is a good concise paper.THIS LINK SAYS IT ALL ABOUT STATINShttp://www.spacedoc.net/mitochondrial_damage_introduction

Bad cholesterol not that bad? Shame on MSNBC...Again!

2010-02-15T06:20:00.001-08:00

When it comes to politics, I do like MSNBC. They are also not bad in delivering the headlines. However, when it comes to health, especially on their web site, they have a long way to go. I am particularly dismayed at their re-purposing of material from other sources. This strategy, used by many other reputable web sites is not in and of itself horrible, but when it comes to health, I am not sure that their editors even read the articles they are posting as their own! This is especially true of material that the post from Men's Health. I mentioned this a while back in my post The truth on the 8 drugs doctors wouldn't take . This was a horrible article that was re-purposed on MSNBC about drugs that were supposedly so dangerous, doctors wouldn't take them. In fact, the authors of the article never asked one doctor when writing this article. I actually did (via Sermo), and found that 7 of the 8 drugs mentioned, most doctors had no problems prescribing.
Now Men's Health is back to their usual scare tactics in an article called "Bad cholesterol: It’s not what you think" which is now a featured article on MSNBC.

Factually, there is nothing wrong with the article. The major point of the article is that the concept of LDL cholesterol being "bad" is oversimplified. In fact, certain LDL particles may actually not be that harmful, whereas other types of LDL cholesterol can be killers. Fortunately, newer technology is becoming more readily available, which may help us customize treatment more accurately.

The problem that I have is the inflammatory language they use, calling the LDL "hypothesis"
"the greatest medical misadventure of our time" One of the paragraphs states that "the LDL hypothesis has also encouraged many of us to swallow the most-prescribed class of drugs in recent history. Americans spent more than $14 billion on LDL-lowering medications in 2008. Whether that money came out of their own pockets — straight up, or through ever-escalating co-pays — or out of the hemorrhaging U.S. health-insurance system known as Medicare, it's a huge expenditure. " In fact, the subtitle of the original article, which is not posted on MSNBC states, "before you swallow what your doctor prescribes, we suggest you read this article." They make it sound like doctors and the medical establishment have duped patients into taking unnecessary and expensive medicines.

With multiple drug advertisements on TV and blame being pointed at drug companies for our rising health care costs, it is not surprising that many people would find this "information" yet another reason not to take medications. The problem with this type of "journalism" is that it can actually harm people. In our media world of soundbytes, tweets and headlines; not everyone reads the entire story. In fact, many patients who need medicines get scared and stop taking them. My reason for posting the initial Men's Health article was because a patient whose horribly controlled asthma had been substantially improved with Advair was in my office sick again because she had stopped taking it. Her reason: her fiancee read the Men's Health article and told her her medicine was dangerous.

Medicine and health is complicated. There are some conditions where medication is overprescirbed (antibiotics for colds) and many chronic conditions like high blood pressure and diabetes which remain out of control and probably need even more medications. In addition, there are certainly a host of drugs proven not to be safe (Vioxx), including certain cholesterol medications (Baychol) which were pulled from the market. However, here is the truth about cholesterol lowering medications:

Currently available cholesterol lowering medications (statins) are the most commonly prescribed medications in the US
Statins are extremely safe. The main side effect is muscle pains which happen in about 3% of patients, are usually mild, and usually go away.
Serious side effects from statins do exist, but happen to fewer than one in a million patients, which is safer then most medications we have.
Statins are likely responsible for the dramatic reductions seen in heart attack and stroke in the US.
Cardiovascular disease (heart attack, stroke) is the single leading cause of death in the US. It beats cancer, diabetes, and accidents...combined!
There are more studies on statins then any other medications
The evidence that statins prevent heart attack and stroke in patients with risk factors is overwhelming.
There is even talk of a polypill that contains multiple medications including a statin, that everyone over 50 would take to prevent heart attacks and strokes.

Bottom Line: We certainly need more tools and techniques to better identify those at risk and individualize treatment. However, currently LDL cholesterol is one of the best markers we have for cardiovascular disease (our country's leading killer) and we have safe and effective medications proven to lower this risk. Do not be afraid of statins.

Shame on MSNBC (again) for re-purposing inflammatory and potentially dangerous information.

Crestor approved for primary prevention

2010-02-09T05:11:00.000-08:00

Today the FDA announced that Crestor (rosuvastatin) is now indicated for primary prevention of cardiovascular disease. I blogged about this a few weeks ago in my post Crestor: Get Ready to Ask Your Doctor for the CRP Test. Which reviewed the advisory board's recommendation to give Crestor this extra indication. Today the FDA made it official.

Specifically, Crestor is now indicated for

" the primary prevention of cardiovascular disease to reduce the risk of stroke, heart attack, and the risk of arterial revascularization procedures (including coronary artery bypass graft, or bypass grafting of a peripheral artery or carotid artery, or angioplasty or stent placement) in individuals who have no clinically evident heart disease but are at an increased risk of heart disease due to the combined effect of the following risk factors:

Age (> 50 years in men; > 60 years in women), and
An elevated high-sensitivity C-reactive protein level (> 2 mg/L), and
Presence of at least one additional cardiovascular risk factor (e.g., high blood pressure, low HDL-C, smoking, or a family history of premature heart disease). "

There are several reasons why this is interesting:

1. It won't be long before Astra Zeneca, the makers of Crestor, advertise this new indication to patients on TV ads. They will likely ask patients to ask their doctor for CRP tests. Not everyone agrees with the use of the CRP test. The US Preventative Health Task Force (same folks that said mammograms under 50 may not be a good idea), also said that there was not enough evidence to test for and treat an elevated CRP. The Jupiter study led to Crestor getting this indication was a large, well done randomized trial and strong enough evidence for the FDA. However, some (like the US task force) don't think one study is enough.

2. Lipitor goes generic within a year. Lipitor is the number one selling drug in the country. A generic version of Lipitor could thus save millions. However, Lipitor does not have the indication for primary prevention of heart disease for patients with relatively normal cholesterol. I have previously blogged about what is meant by "an indication." Essentially, this means that the drug companies can only market to patients and doctors what the FDA says that they can do. Any other claims are considered "off-label" even if there is strong evidence that the medication does indeed work. My favorite example was back when Zyrtec (Pfizer) was a prescription drug and their marketing campaign focused on Zyrtec treating both indoor and outdoor allergies. The reality is that all allergens produce symptoms from histamines, and all antihistamines work the same way. However, none of Zyrtec's competitors (Allegra, Claritin) could make this claim since they did not have the indication. Thus, Pfizer made it sound like Zyrtec might be better than the others, when in fact, there wasn't really a difference.

However, Crestor's indication takes a more substantial meaning with generic Lipitor on the way. Lipitor has not been shown to do what Crestor did and probably never will, since Pfizer chose not to spend the money on this kind of study with Lipitor's patent fading. Unlike the Zyrtec/Allegra comparison, there may be a difference. Only the very potent, high dose statins have shown to substantially reduce CRP and potentially reverse cardiovascular disease. It is likely that Lipitor at an 80mg dose would do the same thing as Crestor 20mg, but could also have more side effects. Once Lipitor goes generic, the insurance companies are going to make it virtually impossible for patients to get Crestor. Yet, for primary prevention (as well as other more agressive lipid lowering goals), Crestor may be exactly what patients need.

3. The cholesterol guidelines that most physicians accept are the Adult Treatment Panel (ATP) III from the NIH's National Heart, Lung and Blood Institute. These guidelines are about a decade old. The most recent update was back in 2004 in response to several important studies. The next version should be up for public comment in just a few weeks, and done by the summer. The FDA's decision today should force the committee (though they would've probably done this anyway) to address the CRP question. It should be very interesting as well to see if they limit treating CRP with Crestor, or generalize this to other statins.

Insurance Free Medicine

2010-01-25T05:51:00.000-08:00

I never thought I would be in academic medicine for so long. When I was hired about 12 year ago, I figured I would stay in academics for a few years and then join a private practice Internal Medicine group. Now, I can't even fathom that idea. One of the reasons I have stayed at my institution for so long is that I love teaching and the academic environment. However, a second reason is that the "real world" for primary care medicine is a scary one. As a salaried employee in a large practice, I am somewhat sheltered from the harsh realities of running a business in the current health care environment. Yet, I hear horror stories from my colleagues in the community that are struggling to survive. With reimbursement rates from insurances so low, and administrative burdens so high, many older physicians have retired and younger physicians have adopted new models of delivering care. These have various names such as "concierge medicine" or "boutique practices".

Though I have no intention of leaving any time soon, I know that (assuming there are not major changes via health care reform) the current model of a small group of primary care physicians who accept insurance is simply not sustainable. Yet, I have a hard time imagining myself practicing in one of these new models, or even attracting patients to my practice. Retainer medicine is one model, where primary care physicians are able to see a much smaller panel size (and thus increase access) by charging patients an annual fee, which ranges from hundreds to thousands of dollars. Though the model makes financial sense, the word "retainer" sounds too legalese for me and likely not easily understood by the lay public. I would prefer something like "membership fee" similar to something would pay to join a club. However, "membership medicine" or "club medicine" just doesn't seem to have a good ring.

"Boutique" practices often use a retainer model, but boutique can also refer to primary care physicians who charge for extra services such as laser hair removal or botox injections. There are many primary care physicians who still take insurance that have started using these kind of practices or have found other ways to meet their bottom line, such as selling nutritional supplements. Though there is no question that the public has a demand for these services, providing them for a fee as a primary care physician seems to carry some conflict of interest, since none of these services show any benefit in overall health. "Concierge medicine" is another term used with retainer models and boutique practices. This implies some sort of preferential treatment, but also usually is associated with "executive physicals" and a battery of unnecessary testing and high technology that again provides little in the way of proven health benefits.

Some physicians have continued to practice normally, but simply do not accept insurance. They have figured out that they can sustain a primary care practice if they simply refuse to accept the substantially reduced rates that insurance companies give them. These are often referred to as cash only practices. Yet, the term "cash only" seems to imply (at least to me) something shady or under the table. In addition, most patients who see cash only physicians, pay for these services using a credit card, making the name somewhat illogical.

However, the reason that all these new models of medicine exist boils down to one single reason: health insurance. Rates from insurance companies are so low, that the only way a primary care physician can make ends meet is to increase volume to the point that both access and care delivery suffer substantially. In addition, the administrative headaches which include fighting to get tests/medicines covered and arguing over claims once submitted, make the practice of medicine less than enjoyable. The often quoted study (that I co-authored) showing that only 2% of medical students are interested in primary care internal medicine, is often used to support the argument that primary care physicians need to be paid more. While the need to substantially reduce the growing income discrepancy between primary care physicians and specialists is critically important, the study actually showed that educational experience, nature of patient care and lifestyle were the primary factors influencing career choice, not income. This was regardless of students' medical school debt. In other words, it was more about the hassles of primary care medicine and less about the how much money they would make, that led students away from careers in primary care.

Thus, I think a term that I would like to propose for use in further discussions of newer ways of practicing primary care (in blogs, media, etc.) is "insurance free medicine." In my opinion, the term "insurance free medicine" captures the essence of the newer models of primary care. Patients have certainly seen their premiums and deductibles increase and can probably relate quite well to reasons why a doctor would not accept insurance. Insurance free primary care practices could certainly adopt retainer membership fees and promote improved access, but eliminating terms like "boutique," "concierge," and "cash only" might help eliminate the notion that primary medical care without insurance is somehow tainted or only for the super-wealthy. In a previous post on KevinMD, I discussed that without substantial changes, primary care will soon go the way of psychiatry in that patients who use their insurance to see a psychiatrist get one kind of care (very brief visits, mostly management by a non-physician) and those who pay their psychiatrist out-of-pocket get the kind of care that we see in TV and the movies. With a more frequent use of the term "insurance free medicine," patients might start realizing that if they continue to pay their primary physician using their health care insurance, they should expect even briefer visits, longer waits to get in, seeing non-physicians, and greater delays getting a return phone call or results back.

Though I have no immediate plans to leave the world of academia any time soon, I could certainly see starting an insurance-free practice if I ever did.

Why You Should Care About Treatment with Monoclonal Antibodies against Clostridium difficile Toxins

2010-01-21T05:47:00.000-08:00

The New England Journal of Medicine just published an article regarding using monoclonal antibodies to treat clostridium difficile toxins (called C.diff). This is a very small study regarding a condition that most people are not familiar with. However, it is very representative of the future of medicine and findings like this have major implications for the cost and delivery of health care.

Monoclonal antibodies are engineered versions of the body's own defense system. They are usually given by injection or infusion. Currently, there are only a few that are used in clinical practice. Remicade (infliximab) is probably the best example, and treats a variety of conditions including psoriasis, arthritis and Crohn's disease. Xolair (omalizumab) is another for asthma. These drugs are not extensively used because of cost, side effects (Remicade can cause serious, life threatening illness) and convenience (Xolair injections are as frequent as allergy shots and no more effective or safer).

C.diff is an intestinal infection that people get after taking antibiotics. Your intestines have normal bacteria that help with digestion (like the Activia adds) and prevent other bacteria, like C.diff from taking over and causing problems. When taking antibiotics you not only kill the bacteria from the infection that is making you sick, you are also killing some of the bacteria that keep you healthy. The stronger the antibiotic(s) and the longer you take them, the more likely you are to get C.diff, which is why we see this in the hospital so often. C.diff is a common complication of a hospitalization, especially if a patient was on antibiotics. In addition, though older, cheaper medications can treat C. diff infections, recurrence of C. diff is not uncommon.
The study in the New England Journal studies 200 patients with a C.diff infection. Half got two monoclonal antibodies to the disease causing toxins made by the C.diff bacteria. The researchers found that the patients who got the antibodies has a much lower rate of recurrence (7% vs. 25%) and re-hospitalization (9% vs. 20%).

The reason you should care about this is because biologics are the wave of the future. Biologics are agents like monoclonal antibodies, blood products, vaccines and gene therapy; that are produced by biologic processes as opposed to chemical processes like most pills that people take today. The days of the blockbuster pills are over. Most pills are generic or will be generic soon. There are very few agents in the drug companies' pipeline. This is why so many drug companies are buying up smaller biotech companies. But more importantly, this is why pharma is so supportive of health care reform and even happy to cover the cost of seniors' medications when they fall into the "donut hole." Pharma realizes that their profits are no longer going to come from single pills that are taken daily by millions of people, but biologics that are taken by a few, really sick people. In addition to potential side effects (often way worse than pills), biologics are very, very expensive. Xolair and Remicade are both about $700 a dose. This does not cover the cost of infusion or injection, which can be quite pricey. Xolair is given every other week for a few years. In the current study, where both groups of patients were already taking the older, cheaper drugs; would it be worth say $1500 extra to reduce the rate of a recurrence by 18%? There are probably about 200,000 cases of hospital associated C.diff infections a year. That's a cost of $300 million! With the rising cost of health care, and efforts to control these costs, be on the look out for biologics.

Comparative Effectiveness: Stroke May Be First

2010-01-17T13:19:00.000-08:00

It is very likely that health care reform will pass in the very near future. If you are one of about 30 million who will now get some form of coverage, one of the many patients with pre-existing conditions that fear a job change due to loss of health care, or a senior citizen that struggles with medicine during the "donut hole" period; this bill will have an important impact on your life. However, for most Americans, passage of a health care reform will have no short term effect. In fact, this will essentially be a major first step in hopefully a long series of moves that will positively impact our entire health care system.

One part of the proposed legislation that may have an important impact in the short term for Americans not the aforementioned categories will be comparative effectiveness. I have blogged about comparative effectiveness in the past. Essentially, there is money in the proposed legislation that will have the government do studies comparing two agents or devices to see if the newer medication/device/procedure is worth paying for over the current standard of care. This is extremely important, since most studies regarding treatment are funded by the drug and device companies. Not that these studies don't have merit, but many important studies such as comparing two existing treatments are never done because a negative study is generally not worth the financial risk for the company. See what happened to Merck's stock when the ENHANCE study failed to show that Vytorin was any better that generic simvastatin.

However, there are potential issues to comparative effectiveness as well. Many future decisions on what the government will pay for will be based on this research, and what the government feels is worthwhile may be different than patients with a given disease or condition. The US Preventative Health Task Force is the government agency that recently stated that some mammograms are not worthwhile. There were many women upset about this. The first area that you might see, assuming an agency is set up soon, is with stroke.

Patients at risk for stroke generally take a blood thinner called warfarin. Warfarin is essentially rat poison (not kidding here) that thins the blood, prevents it from clotting, and because of this prevents stroke. It has been proven to save lives. The problem with warfarin is that is has what's called a narrow therapeutic window. This means the dose has to be just right. If the dose is too little, the blood is not thin enough and a stroke could follow. If the dose is too high, a patient could bleed to death. In order to get the dose just right, patients have their blood checked on a regular basis, usually once or twice a month. This is quite inconvenient, but potentially life saving.

A new drug, that will likely soon be approved by the FDA (already approved elsewhere) is called dabigatran. Dabigatran works is a different way so that the blood does not have to be monitored. The heart.org is an excellent source of the latest information in cardiology (need to sign up for free to get the articles). They do a great job of discussing the outcomes of the Re-LY study, which compares dabigatran to warfarin. This was a large study with over 18,000 patients at risk for stroke. The study showed that at the higher dose, dabigatran was better (prevented more strokes) than warfarin, and there was no more bleeding events compared to warfarin, i.e. it was just as safe. In fact, the worse complication feared is hemorraghic stroke (bleeding into the brain) and this was better with the new drug. Thus, the new drug is just as safe or possibly safer, and works better, and patients don't have to go to their physician's office twice a month to get their blood checked for the rest of their lives. Thus, it should be a slam dunk that dabigatran is used over warfarin, right? Here's the problem: warfarin is cheap as dirt, pennies a day; dabigatran will likely be quite expensive, potentially dollars a day. Will the government, based on this kind of comparative effectiveness research, be willing to pay for the better drug? Probably not, since so many patients are currently on warfarin. It will probably come out with something along the lines of that it will pay for it, but only for patients who have problems with warfarin.

In an effort to control health care costs, these are the kind of conversations that you should expect to hear in the not to distant future.