Evidence-based Medicine
The Great Statin Debacle
February 3, 2008
With the publication recently in BusinessWeek exploding the story about Vytorin, it is time to examine the role of statins, cholesterol, and heart disease. The results of the new drug trial, termed the ENHANCE study, which tested a combination of Zetia (ezetimibe), manufactured by Schering Plough and Merck, and Zocor (simivastatin), manufactured by Merck, were scheduled to be published in early 2007, but this was delayed. A press release on January 14, 2008 indicated that there was no benefit to be derived from the combination. Indeed, the randomized controlled trial, which randomly allocated either Vytorin (10/80 mg) or Zocor (80 mg) to 720 patients that had heterozygous familial hypercholesterolemia–a rare condition present in about 0.2% of the population–and measured the intima-media thickness (arterial wall thickness) at 3 sites in the carotid arteries of patients found that wall buildup increased by 0.0111 mm for the Vytorin-treated group, nearly twice of that of the Zocor-treated group (0.0058 mm). These results were not statistically significant, meaning that the probability of the difference happened by chance. (In statistics, we often use a probability of .05 as the minimum evidence that two results in a trial did not occur by chance, but were due to some effect.) The full results of the enhance study will be presented at the American College of Cardiology meeting in March, but probably won’t be published in a medical journal until the end of the year. Meanwhile, more trials of Vytorin are planned. I guess the drug companies are happy to spend your money on worthless trials, because they have invested so much time, money, and effort in them. So, are statins a complete waste of time and money? This depends in part on whether you believe the cholesterol “hoax.” Why do I say hoax? All the statins were developed on the principle that high cholesterol—specifically, low density, also know as “bad” cholesterol—is one of the major causes of heart disease. If you believe this, then we might as well believe the tooth fairy is real. Start by reading Anthony Colpo’s article about the myth of bad cholesterol published in Journal of American Physicians & Surgeons. If you want more evidence, go read the article by Krumholz et al. published in JAMA in 1994. (And if that doesn’t satisfy you, write me an email and I’ll send you a bunch more references.) But, let’s pretend for the sake of argument that lowering cholesterol has some merit, and your physician, who has been liberally supplied with both samples and literature, checks your cholesterol and finds it’s high. You take a statin and deal with the side effects, the muscle pains, and so forth, and the increased risk of cancer (your doctor surely knew about that, and told you, didn’t he/she?) and wait for the drug to work. A few months later, your cholesterol comes down. Problem over, right? Wrong! Statins do lower cholesterol, but except in 1% of cases, they won’t stop you from getting a heart attack. How do we know that? Because of something called the NNT. The NNT, or number needed to treat is a parameter that is not often quoted in many drug trials, although it should be. It is basically the mean or average number of patients that have to be treated to in order to have 1 additional event happen. So, if you treated patients with an antibiotic for some infection, and the event was “cure,” and the NNT was 2, then that would mean that for every 2 patients treated, 1 would be cured of the infection. That’s a pretty good number. What’s a typical number for a statin? It’s about a 100 in regard to the mortality of coronary heart disease (see Table 2, statins). So for every 100 patients, we might expect 1 person to benefit. One! And this number does not take into account the number of people in that group of 100 who might be harmed by the drug, which is the number needed to harm. Statins do actually have some interesting anti-inflammatory properties and have even been proposed as treatments or prophylactics in avian influenza (H5N1). But that’s another story. So, what’s my advice? Unless you already have severe coronary heart disease, and actually might be a candidate for statin treatment, ignore the cholesterol mantra and stay away from statins. If your physician insists that your cholesterol is high and needs statin treatment, ask him or her to read some of the literature we have cited. See if your doctor understands about the NNT parameter. In terms of heading off cardiovascular disease, you are far better off leading a healthy lifestyle (no stress, now!) and eating a balanced diet free from processed foods. Consider taking supplements of unadulterated omega-6 and omega-3 cold-pressed oils in about a 2.5 or 3:1 ratio.
Marissa J. Carter, PhD