A study came out a couple of weeks ago that has thrown the statin worshipers into a blind panic. The study, published in an obscure journal, indicates that people who have low LDL-cholesterol (LDL) levels have a higher risk of developing Parkinson’s disease (PD). The authors of the study didn’t actually test to see if statin drugs caused the lower LDL levels that are associated with PD, they simply made the case that patients with PD have lower LDL levels than those who don’t. In fact, the control group (the subjects without PD) contained many more people taking statins than did the study group of patients with PD, which could conceivable lead to the conclusion that statins somehow prevent PD. The authors made such a case:

In summary, our study shows an association between lower LDL-C and the occurrence of PD. This may be interpreted either as linking lower LDL-C levels etiologically to PD, or as cholesterol-lowering agents having a neuroprotective effect as regards PD. [My bold]

Despite the authors making this statement and the data itself showing what could be considered a protective effect, the pro-statin folks went ballistic. Just the idea that perhaps lowered LDL might be a factor in PD was enough to set them off at full bellow on the idea that should people actually believe this and stop taking statins, thousands of them–no, millions–might die of heart disease and/or stroke.

Dr. Peter Weissberg leads the pack.

There is no evidence to suggest that statins cause Parkinson’s disease. There is, however, overwhelming evidence that statins save lives by preventing heart attacks and strokes.

Nobody should stop taking statins on the basis of this report. If they do, they will be putting themselves at increased risk of heart attack or stroke.

Dr. Peter Weissberg is the head of the British Heart Foundation, an independent funding organization that provides considerable money to UK research on cardiovascular disease. The British Heart Foundation is also funded by, among others, companies that make statins. If you look up Dr. Weissbergs papers, you’ll find that most are underwritten by the British Heart Foundation and sometimes makers of statins as well. It would not be in Dr. Weissberg’s best interest for people to stop taking statins.

But what about the people who are taking statins. What’s in their best interest? Statins are extremely expensive and are not without side effects. In fact, some of the side effects are fatal. So, again, what about the people taking statins? Are they getting their money’s worth of protection against heart disease? And are the risk of side effects offset by the decrease in risk for heart disease? Let’s take a look.

In 2001 probably the most momentous publication in medical history occurred. It was momentous not because it was of astounding importance like Einstein’s four papers in 1905, but momentous because it has ended up affecting so many people. The document is the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults, produced as part of the National Cholesterol Education Program. The goal of these guidelines is to markedly decrease the incidence of coronary heart disease (CHD). How is this goal to be accomplished? First, by a regimen of low-fat dieting combined with exercise. But if this regimen should fail to lower LDL levels to below 130 mg/dL (more than half of adults over age 35 have LDL levels of 130 mg/dL or higher), then the guidelines recommend treatment with statin drugs to prevent CHD. Readers of this blog know how great the chances are of a low-fat, high-carb diet lowering the LDL to sub 130 mg/dL levels, so these recommendations are tantamount to recommending the use of statins to more than 50% of adults over the age of 35.

I don’t know the exact number of people over age 35 in the United States right now, but I think it would be safe to say that there are at least 100 million. Half that number is 50 million, which would represent the population of adults over 35 with LDL levels of 130 mg/dL or greater. Now, let’s make a big assumption and say that a third of that 50 million can lower their LDL levels with a combination of diet and exercise (highly unlikely, but lets say it just for grins), that leaves us with about 34 million people who–according to the recommendations–should go on statin drugs. Statin drugs cost, depending upon the brand, somewhere between $2.66 and $4.86 a day, so let’s average it out to $3.75 per day. If we multiply $3.75 per day times 365 days per year times 34 million people we end up with $46.537 billion per year, a tidy little sum that will find it’s way into the pockets of Big Pharma should these recommendations be carried out. (Of interest is the fact that in the paper on low LDL and PD that started this post, the average age of the control subjects was 66.7 and 34% of them were taking statins, so the numbers I’m postulating on numbers of people taking statins are pretty much right on the money.)

If you divide this $46+ billion by 453,189 (the number of people who died from CHD in 2004 from the last available statistics) you come up with a cost of $101,923, which would be the cost per year per person saved by statin drugs if those drugs could somehow prevent every single death from CHD. Now multiply this $101,923 times the number of years the average person would have to take these drugs to prevent death, and you come up with some hefty figures. Probably well over a million dollars per person saved. Is it worth it to society to pay that much? Remember, we all pay for this either directly if we take statins or through increased insurance premiums because of others who do. And we really have to ask that question because most of the deaths from heart disease are self inflicted.

Why self inflicted? Because by far the major cause of CHD is smoking with high blood pressure running a close second. I’ve thought back on all the people I know who have had heart attacks and on all the patients I’ve cared for who have had heart attacks, and all of them – 100% – were smokers. I’ve called a couple of colleagues and asked the same question and have gotten the same answer: people who have never smoked and who have heart attacks are scarce as hens teeth. They exist, to be sure, but they are in the minority. Think back about the people you know who have had heart attacks, and I suspect you will realize the same thing. There is a correlation for you. Smoking equals heart disease. Not cholesterol equals heart disease. Michael DeBakey, the Houston heart surgeon who pioneered bypass surgery,once famously remarked that at least half the patients he operated on had low cholesterol levels.

So, why should we as a society spend over $100,000 per year to prevent one self inflicted death from heart disease? And remember, that figure is only good if we prevent every single death from heart disease. What if we only prevent half? Then the price goes up to $200,000 per year per death prevented. What if we only prevent 25% of deaths, then the price goes to $400,000. It would be nice to know how many deaths we prevent if we give a third of the population statins. Let’s take a look.

We can look in a couple of places. First we can look in the executive summary of the full 2001 report. This 12 page summary, published in the May 16, 2001 issue of Journal of the American Medical Association (JAMA), gets right to the point. The recommendations of the full report

expands the indications for intensive cholesterol-lowering therapy in clinical practice.

In other words, the recommendations increase the number of people and conditions that need statin-driven cholesterol-lowering therapy. As you go through this executive summary it becomes clear that the authorities believe that cholesterol-lowering is extremely important in both the primary and secondary prevention of CHD and that statins are the way to lower cholesterol.

Who wrote this executive summary? A long list of esteemed experts in the field of cholesterol study. Do they have any conflicts of interest? Let’s take a look. Here is the list of members on the panel that produced the summary:

Scott M. Grundy, MD, PhD (Chair of the panel), Diane Becker, RN, MPH, ScD, Luther T. Clark, MD, Richard S. Cooper, MD, Margo A. Denke, MD, Wm. James Howard, MD, Donald B. Hunninghake, MD, D. Roger Illingworth, MD, PhD, Russell V. Luepker, MD, MS, Patrick McBride, MD, MPH, James M. McKenney, PharmD, Richard C. Pasternak, MD, Neil J. Stone, MD, Linda Van Horn, PhD, RD

Here is the financial disclosure:

Dr Grundy has received honoraria from Merck, Pfizer, Sankyo, Bayer, and Bristol-Myers Squibb. Dr Hunninghake has current grants from Merck, Pfizer, Kos Pharmaceuticals, Schering Plough, Wyeth Ayerst, Sankyo, Bayer, AstraZeneca, Bristol-Myers Squibb, and G. D. Searle; he has also received consulting honoraria from Merck, Pfizer, Kos Pharmaceuticals, Sankyo, AstraZeneca, and Bayer. Dr McBride has received grants and/or research support from Pfizer, Merck, Parke-Davis, and AstraZeneca; has served as a consultant for Kos Pharmaceuticals, Abbott, and Merck; and has received honoraria from Abbott, Bristol-Myers Squibb, Novartis, Merck, Kos Pharmaceuticals, Parke-Davis, Pfizer, and DuPont. Dr Pasternak has served as a consultant for and received honoraria from Merck, Pfizer, and Kos Pharmaceuticals, and has received grants from Merck and Pfizer. Dr Stone has served as a consultant and/or received honoraria for lectures from Abbott, Bayer, Bristol-Myers Squibb, Kos Pharmaceuticals, Merck, Novartis, Parke-Davis/Pfizer, and Sankyo. Dr Schwartz has served as a consultant for and/or conducted research funded by Bristol-Myers Squibb, AstraZeneca, Merck, Johnson & Johnson-Merck, and Pfizer. [My bold type]

So, you’ve got about half the panel – including the Chair – who are, like so much lint, buried deep in the pockets of the pharmaceutical companies that make statin drugs. Do you think these folks might have a motivation to promote the products of the companies that are paying them a lot of money?

But, you say, these people are only summarizing the contents of the real report as an executive summary. They don’t have any say in the data that the report contains. True, but this is where the plot thickens.

The executive summary is 12 pages long and was published in JAMA, which is sent to every physician in America free of charge. The real report is 284 pages long and has to be pulled down from online or ordered from the government. (If you go to the website referenced in the executive summary to get the full report, you are sent here. See how much time it takes you to find it) Which of the two do you think most physicians read? Why should they read the full report when the prestigious authors of the executive summary assure them that

The full ATP III document is an evidence-based and extensively referenced report that provides the scientific rationale for the recommendations contained in the executive summary.

That says it all. According to the executive summary, the full report is like Fox News purports to be: fair and balanced. And the executive summary is then a fair and balanced report of a fair and balanced report.

What do we find when we read the full 284 page report (which you can get here)?

We find that the full report presents a totally biased misrepresentation of the underlying scientific material and seems intent on promoting the use of statin drugs despite any evidence to the contrary. Not the “evidence-based and extensively referenced report that provides the scientific rationale” for statin therapy that the executive report would have us believe.

Before we get into some of the specifics of this full report, let’s recall that the Framingham data, the Queen Mother of all dietary cholesterol studies, didn’t show a correlation between diet and cholesterol, cholesterol and heart disease, nor diet and heart disease. And we need to remember that, despite all the hoopla about statins and lowering cholesterol levels, that cholesterol is an extremely important molecule. The brain is rich in cholesterol, the sex hormones are made on a cholesterol structure, and even vitamin D is built on cholesterol. Consequently, statin drug use has been associated with decreased cognitive ability and sexual dysfunction. Statins can cause liver damage and the breakdown of muscle tissue, both of which can lead to death. In my opinion, these drugs would have to lead to huge reductions in risk for death from all causes to overcome the risk one accepts by taking them.

Let’s digress for a moment and discuss all-cause mortality. Let’s say we’ve got a drug that studies show decreases the risk of death from heart disease by 50%. Let’s say that the only half the subjects in study who are taking that drug die of heart disease as compared to those subjects in the control group. At first blush, it appears that we’ve got a great drug on our hands. But, what if the same number of subjects die in both groups? The study group has way fewer deaths from heart disease but has a lot more deaths from cancer so that the total number of deaths in both groups is the same. This would mean that the people taking the drug traded their decreased risk for death from heart disease for an increased risk for death from cancer. The all-cause mortality didn’t change. All that changed was the cause of death. If we had a drug that brought about the 50% decrease in heart disease deaths in the study group and no increased death from other causes, giving a big decrease in all-cause mortality, then we have something.

The full report looks at both primary prevention against heart disease in men and women under the age of 65 and over the age of 65. And it looks at secondary prevention for men and women who already have heart disease. (Primary prevention is prevention against the development of heart disease in the first place; secondary prevention is prevention against having a heart attack in someone who already has heart disease.)

This post has dragged on long enough, so I’m going to briefly summarize the findings.

In men under 65 with no known heart disease but with risk factors, i.e. LDL of 130 mg/dL or greater, the studies cited showed no difference in all cause mortality. For those men under 65 who had very high LDL levels, the evidence showed that these men might have a slight benefit from taking a statin, but nothing to write home about. Certainly nothing that would justify putting a third of the population on statins.

In women who are under 65 there is virtually no evidence that statins do squat. In fact, the report doesn’t even produce evidence that cholesterol lowering does anything for women. The report states that it bases its rationale for treatment of women on an extrapolation of data from men.

In men and women over 65 the studies cited show no evidence that cholesterol lowering brings about any significant decrease in risk for heart disease. (Remember the 34% of subjects, average age 66.9, in the control group of the PD study mentioned at the start of this post who were on statins. According to the papers cited in this full report, none of those subjects could expect a decreased risk for CHD by taking the statins, but based on this report’s false reporting of the conclusions of these papers, a third of these folks are on statins.)

Men of all ages with diagnosed heart disease were the only group that the studies used in this report show receive an actual benefit from taking statins. And even that is slight.

Women who have heart disease and who take statins have a reduced death rate from heart disease but no decrease in all-cause mortality.

So there you have it. The giant report that, thanks to the executive summary, has driven most physicians in America to prescribe statins to practically everyone who walks through the door shows, when the data is examined, that statins are only really indicated in men who already have heart disease. They don’t do much for anyone else but put them at risk for a host of other problems while running health care costs through the roof for the rest of us.

Who could possibly benefit from this situation? How about the underwriters of the whole scheme: the drug companies and the ‘experts’ on their payroll.

We’ve got a situation where ‘experts’ paid by the drug companies write an executive summary about a report written by ‘experts’ paid by the drug companies, a report that misinterprets (purposefully?) the underlying data to make the case that the drugs made by the drug companies paying the ‘experts’ are under prescribed. Others jump on the bandwagon, making pronouncements, based on this faulty reporting, that almost everyone should be taking these drugs made by the drug companies that underwrote the entire enterprise. One buffoon, cloaked in all the trappings of academia, even made the comment that since statins are so wonderful perhaps they should be added to the drinking water. As a consequence, we’re paying billions of dollars for drugs that don’t particularly work and that cause a number of pretty bad side effects to prevent a disease that can be prevented by fairly simple lifestyle changes. Pitiful.

Is it any wonder that Dr. Weissberg got his panties in a wad when he thought a study might persuade people not to take statins. Based on what you know now, go back and read his comments to the BBC. And get mad.