Thursday, February 25, 2010

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

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.

Sunday, February 21, 2010

More Avandia Scare- Again, Unwarranted.

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 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.

Thursday, February 18, 2010

FDA Blows it on LABA Safety

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.


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 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.


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.

Wednesday, February 17, 2010

What every medicine cabinet needs

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:
Hydrogen peroxide
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

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.

Tuesday, February 16, 2010

Lipitor: Responding to Space Doc

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 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 STATINS

Monday, February 15, 2010

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

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.

Tuesday, February 9, 2010

Crestor approved for primary prevention

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.