Do Not Stop Your Statins

As my tween daughter would say, "OMG!"
The media is a buzz with the news that the FDA is changing the warnings on statins.
The New York Times claims "Safety Alerts Cite Cholesterol Drugs’ Side Effects."
According to the Wall Street Journal "FDA Warns on Statin Drugs."
And the text on the bottom of the CNN report states "FDA places warning on statin labels."

Statins, which are cholesterol lowering medications are now one of the most commonly prescribed medications in the US. If I were one of the millions of patients taking a statin, I would be pretty worried based on what I am hearing from the media. 

Fear Not!  There is Nothing to Worry About.  Do Not Stop Your Statins!

Before getting in the details, it is important to note:

1. It is pretty irresponsible of the media to use scary headlines, when the warnings from the FDA weren't really that bad.  In addition, the warnings about liver problems (the one you hear about in all those TV commercials) were actually downgraded. 

2. It is not entirely the media's fault.  The FDA does a very poor job when releasing information.  When they update something, they should make it clear to physicians and patients what the real risk is.  Once again, the FDA failed miserably.

3. Statins are probably some of the safest medications we have. If patients could easily perform and interpret their own blood work, these might even be over the counter.  Some have suggested that this might be a good idea. Moreover, statins reduce heart attacks and strokes (#1 and #4 killer in the US). Though no medication is perfectly safe, I can think of no other long term medication where the risk benefit ratio is so far in favor of the drug. Cardiologist John Mandrola put this best in his post (via KevinMD) "Let's close the chapter on statin safety." 

Ok, now for the details. 

Today the FDA released information that they were updating warning information on statins. Essentially, there are three areas where safety data was updated: liver enzymes, memory impairment and diabetes.

Liver enzymes- This one is actually good news. Earlier statins caused some elevations in liver enzymes which were feared to potentially cause liver damage.  After many years of usage, it doesn't seem this fear is warranted.  Because they can affect the liver, patients with pre-existing liver disease should use statins cautiously. Even though statins can cause liver enzyme elevation, it is usually at the highest doses and usually returns to normal when the statin is stopped of the dosage is lowered. The routine monitoring of liver enzymes that was once recommended is now no longer required. 

Memory Loss- This is the one that makes me the most annoyed. First, because it really isn't true and second because the way the FDA communicated the data is useless at best and harmful at worst, since patients may stop taking statins because they are afraid that they will get Alzheimer's. 

According to the release the

"FDA reviewed the AERS database, the published medical literature (case reports and observational studies),^4-13 and randomized clinical trials to evaluate the effect of statins on cognition.^14-17"  

The numbers above refer to references of studies they looked at. However, of the 13 studies they analyzed "did not suggest that cognitive changes associated with statin use are common or lead to clinically significant cognitive decline." In fact, most of these studies were looking at use of statins to PREVENT Alzheimer's. Thus, most of the data they used to make this recommendation was from their own AERS database.  It would have been really nice to release this data! However, one of the mentioned publications did look at MedWatch drug surveillance system of the Food and Drug Administration (FDA) from November 1997–February 2002 for reports of statin-associated memory loss.  Of course we don't know the exact number of patients that took a statin during those 5 years, but it was in the millions.  The authors were only able to find 60 reports, of which none was truly confirmed (just patient report) and more than half noted improvement when the statin was stopped. 

I have previously blogged about this issue back in 2008 in my post Lipitor and Memory Loss as well as another post Lipitor: Responding to Spacedoc. Spacedoc is really Dr. Duane Graveline, MD, MPH, a family physician who became a NASA's scientist, but is better known for his book "Lipitor, Thief of Memory" which he wrote after having two episodes of something called transient global amnesia (TGA) which he states was associated with his use of Lipitor from 1999 - 2000. In fact, I actually became aware of TGA because the mother of a close friend had the exact same thing. 

Bottom Line- There may be some connection between Lipitor and memory loss. However, even if there is, it is extremely rare (you have a better chance of winning the lottery) and even if you get it, it usually goes away if you stop the medication. In other words, there is absolutely no reason to be alarmed, and no reason not to take the drug if you need it to control your cholesterol. 

Diabetes- This is another topic that I have blogged about, and one that seems not to want to go away.  You can see my post "Statins Don't Cause Diabetes" for all the details.  Much of the concern came from a Crestor trial which actually showed Crestor to cut heart attack risk in half in patients that had relatively normal cholesterol.  This study used a particularly high dose of Crestor, and the FDA warnings point to other studies using high dose statins with similar findings.  It is important to note that in the Crestor study, about 40% of the patients were at risk for developing diabetes in the first place, that measures of diabetes in the study were really no different, but the physician reported (i.e. unconfirmed) rates of diabetes were increased.   However, more importantly, if you look at the actual rates of developing diabetes it was 3% in the Crestor group an  2.4% in the placebo group.  In other words, if statins increase your risk of developing diabetes, it increases it only by 6/10 of a percent (not as low a winning the lottery/memory loss, but pretty darn low). However, with millions taking a statin, even a small risk is something to consider.  However, one must also note that diabetes is a disease process more than just an isolated sugar number, and it is unclear what actual risk a statin would cause by turning a pre-diabetic patient into a diabetic one.  In fact, patients who are pre-diabetic have a 4 to 6 times greater risk of heart attacks and strokes, and statins have been used in pre-diabetic patients and shown to reduce their risk of heart attack and strokes.  Conversely, no study has shown that reducing sugar in a diabetic reduces their risk of heart attack and stroke. 


Bottom Line-statins may raise your sugar a tiny bit, and for those patients who are at risk for developing diabetes, taking a high dose statin may "push" that patient into having diabetes sooner than expected.  However, even in that circumstance, the statin is probably still well worth the risk since it is potentially preventing a heart attack or stroke and slightly increasing the sugar probably has no clinical ramifications. 

All In For Crestor

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.

Lipitor or Crestor for LDL's above 160

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.

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.

Comparative Effectiveness: Stroke May Be First

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.