BITTERSWEET MEDICINE

Overrated Medications Series: No. 2 Statins For Primary Prevention of Cardiovascular Diseases

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708px-rca_atherosclerosis.jpg-w=300&h=253Facts are stubborn things, but statistics are more pliable. — Mark Twain

This post is blasphemy.  Fortunately I am in good company.  I offer nothing new here for well read physicians and patients.  I have no original ideas to present.  My hope is to help spread the word.  I, like most primary care physicians, had the “statins are good, add them to the drinking water” mentality drilled into my head at lectures paid for by Big Pharma.  Eloquent cardiologists with rapier wit expounded on the studies while I dined on filet mignon and pinot noir.  I left the lectures after hearing impressive risk reduction numbers like 33% for cardiovascular death and 22% for all cause death.   What I didn’t learn was the difference between the relative risk reduction and the absolute risk reduction and concepts like number needed to treat.  Like most family physicians (and other specialists I suspect) I never read the actual studies.  I just accepted what the speakers paid for by Big Pharma told me.  I woke up when I read two books which I recommend to you: Worried Sick by Nortin Hadler and Overdosed America by John Abramson.  If you can let go of your emotions and be objective these books are splendid road maps for skeptical patients that are proactive for their own health.

Statins are drugs which lower cholesterol levels by decreasing cholesterol synthesis in the liver.  I think every American knows these drugs.  To name a few: Lipitor, Pravachol, Crestor and Zocor.  Plaques in coronary arteries are largely composed of cholesterol.  Lowering cholesterol will in theory and in fact cut the rate of formation of plaque and in some cases shrink plaque.

There are two kinds of heart disease prevention.  In primary prevention statins are given to people without known coronary artery disease to prevent heart disease or heart attack.  In secondary prevention statins are given to people with known coronary artery disease or those who have had a prior heart attack to prevent another heart attack (in some cases a first heart attack).  There is a big difference between the two. Primary prevention has little benefit, secondary prevention has great benefit.

Let’s start with the most well-known statin study of all: The West of Scotland Coronary Prevention Study.  The patients in this study had very high cholesterol levels with a total cholesterol averaging 272 mg/dl and an LDL (bad cholesterol) averaging 192 mg/dl and an HDL (good cholesterol) averaging 44 mg/dl.   There were 6,595 subjects in the study, about half received Pravachol and half placebo.  44% of the patient’s smoked and 16% had high blood pressure.   (If I may pontificate, smoking is a far greater risk factor than high cholesterol and smoking cessation is of far more benefit than taking a statin).   After almost 5 years the relative risk reduction of all cardiovascular deaths was 32% (statistically significant) and relative risk reduction of all cause death was 22% (not statistically significant, but close).  Sounds impressive, yes.  But absolute risk reduction of all cardiovascular death was only 0.7% and absolute risk reduction of all cause death was only 0.9% over 4.9 years (see chart).  Thus, 100/0.7 = 142 men have to take Pravachol for nearly five years to prevent 1 cardiovascular death and 100/0.9 = 111 men have to take Pravachol for  nearly 5 years to prevent 1 death overall.  The study itself sums it up:  “it can be estimated that treating 1000 middle-aged men with hypercholesterolemia and no evidence of a previous myocardial infarction with pravastatin for five years will result in  . . . 7 fewer deaths from cardiovascular causes, and 2 fewer deaths from other causes than would be expected in the absence of treatment.”

The reason I started with the West of Scotland Study is because it supports statin use more than any other primary prevention study I know of.  The patients in this study were very high risk, yet the intervention did not help much.  Subsequent studies have not done even as well as the West of Scotland Study.  Some studies have found no benefit from statins in primary prevention.

Here is another statin study, the AFCAPS/TexCAPS study.  Read through it.  Here is a quote directly from it, copied and pasted: “The overall mortality rate was similar in each group, with 80 deaths among participants treated with lovastatin and 77 deaths among participants treated with placebo (4.6 and 4.4 per 1000 patient-years in participants treated with lovastatin and placebo, respectively).” Were you able to find that quote?  Hard to find isn’t it?  Wonder why?  Why wasn’t a statistic as important as overall mortality included in the abstract?  Is my thinking on the subject wrong?  If overall death rates are equal, does it matter what the cause of death is?

Here is another statin study, the PROSPER study published November 23, 2002.  This study looked specifically at the elderly.  It was sort of hybrid study as the participants were a mixture of people with known coronary artery disease and no known coronary artery disease. Patients were also generally high risk for coronary artery disease.   Approx. 25% smoked, ~10% had diabetes, ~25% had angina and ~13%  had prior heart attacks.  The PROSPER study is available on-line from The Lancet and is free, but you will need to register an account to read it.   Although not mentioned in the abstract, here is a quote directly from the article: “There was no observed difference in all-cause mortality.” Once again I ask, if mortality is the same in both groups, does it matter what the cause of death is?

Here is a meta-analysis that agrees with me.

Read my Crestor post.

I’m going to stop now and let my readers look into it further on their own.  Read the primary prevention studies, like ALLHAT.  Forget the relative risk reduction, look at the actual percentage differences between the treated and placebo groups.  Divide the difference into 100 and you will get the number needed to treat over the length of the study.  Notice if the abstract mentions overall mortality; if it was favorable it will always be mentioned.  If unfavorable it might be buried in the article.

Another point I would like to mention is that the writers of the National Cholesterol Education Panel (NCEP) guidelines have financial ties to Big Pharma. This explains some of what you have read here.  Still, I do follow the NCEP guidelines.  The guidelines are actually reasonable. With Framingham risk calculation and stratification based on family history and coronary disease equivalents, I find I prescribe statins a lot less often than I did in the days when I just looked at a patient’s cholesterol levels and guessed.  I also give patients the number needed to treat.  A math professor declined treatment based on that once.

Don’t forget, we’re talking primary prevention here.  If you are very high risk, middle-aged and known to have coronary artery disease, then this does not apply.

Also don’t forget I’m not your doctor. This is not health advice.  This is information for those interested in heath and well-being, but you need a face to face encounter with a physician and an exam and history and physical before making any decisions about medications or treatment.

Written by admin

March 26th, 2010 at 9:56 am

Posted in Family Medicine

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