The Great Cholesterol Myth (21 page)

Worth noting: Of the fourteen authors credited in the ASCOT-LLA study, all of them served as consultants to—and received travel expenses, speaking fees, or research funding—from pharmaceutical companies marketing cholesterol-lowering drugs, including Merck, Bristol-Myers Squibb, AstraZeneca, Sanofi, Schering-Plough, Servier, Pharmacia, Bayer, Novartis, and Pfizer. Pfizer (maker of Lipitor) was the principle funding source for the study. That fact alone certainly doesn’t make the results invalid, but it’s still worth mentioning.

The Heart Protection Study (HPS) divided more than twenty thousand adults with either coronary artery disease or diabetes into two groups and gave one group 40 mg of the statin Zocor daily while the other group received a placebo.
²⁸
It was claimed that “massive benefits” were obtained by lowering cholesterol with the statin drug, and indeed fewer people died in the Zocor group than in the placebo group.

But let’s look at the absolute numbers. Those in the Zocor group had an 87.1 percent survival rate after five years, but those in the placebo group had an 85.4 percent survival rate, an absolute difference of 1.8 percent. Most important, the survival rates were independent of lowering cholesterol. In other words, lowering LDL levels made essentially no difference in the risk of death from heart disease. (This is not difficult to understand when you factor in the other things statins do besides lower cholesterol. If anything, it simply shows that statin drugs may be useful in certain populations, but if they are, it’s independent of their ability to lower cholesterol. In fact, it increasingly looks like lowering cholesterol may be the least significant thing statins do.)

As Uffe Ravnskov, M.D., Ph.D., stated in a letter to the editor of the
British Medical Journal
regarding the Heart Protection Study results, “Tell a patient that his chance not to die in five years without statin treatment is 85.4 percent and that [statin] treatment can increase this to 87.1 percent. With these figures
in hand I doubt that anyone should accept a treatment whose long-term effects are unknown.”
²⁹

In this trial, more than forty-seven thousand patients received Zocor over the course of six years. There was quite a variety in their response to this treatment. Some folks saw dramatic lowering of their LDL levels, some saw a moderate fall in their levels, and some experienced essentially no reduction in their levels.

After five years, the researchers examined the death rate among the participants and cross-referenced these deaths with the patients’ LDL levels. You’d think this would be the perfect study to demonstrate a correlation between lower LDL levels and a decreased risk for heart disease, right? Clearly, those whose LDL levels had dropped dramatically would have been far more likely to live, while those whose cholesterol levels had not dropped at all would have been far more likely to die, and those who had lowered their cholesterol only a modest amount would have fallen somewhere in between.

We’re sure that’s what the researchers expected to see.

But they didn’t.

After five years there was exactly no correlation between LDL levels and death rate in the three groups. In other words, whether your cholesterol had been lowered or not had no correlation to whether or not you died. Patients with the highest levels of LDL died at pretty much the exact same rate as patients with the lowest LDL levels (and as patients with LDL levels in between the highest and the lowest). Bottom line: Lowering LDL levels didn’t give you even a drop of protection against dying.

The Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) was interesting for a number of reasons. In this study, older patients were divided into two groups. The first group consisted of patients with no history of heart disease (primary prevention group), and the second group consisted of patients with current or past cardiovascular disease (secondary prevention group). Half of each group received Pravachol (a statin drug), while the other half received a placebo.

There was some reduction in heart attacks or strokes, but only in the secondary prevention group (those who had current heart disease or a history of heart disease). There was, however, no reduction in heart attacks or strokes in the primary prevention group, the group that had no history of heart disease to begin with. This is pretty much in keeping with the findings of the vast majority of other studies.

But there were two other interesting findings, one of them quite troubling.

When pharmaceutical reps spin the data from the PROSPER study, they concentrate on the single fact that Pravachol reduced heart attacks and strokes (while downplaying the fact that it did so only in the group that already had heart disease). Okay,
that’s good; the prevention of a few heart attacks and strokes, even in a limited population, is always nice. But what about other measures of health, disease, and well-being besides heart attacks and strokes?

To answer this question, researchers decided to look at other measures of total health impact. They looked at “total deaths” and “total serious adverse events” and found that both were completely unchanged by Pravachol. Once again, a statin drug had a beneficial effect on heart attacks and strokes in the secondary prevention population but not in the primary prevention population, and once again, not a single life was saved overall.

The second finding was more troubling. Both groups receiving Pravachol had an increased risk of cancer. Amazingly, the investigators simply dismissed this statistically significant finding as “the play of chance.”

We saved this one for last, because it’s the juiciest, most perfect example of utter cholesterol madness, media hype, behind-the-scenes manipulation, and intellectual dishonesty.

If you read the papers or watched the news in 2009, you probably heard about this study, though you may not have known what it was called. Its name—JUPITER—stands for the Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin. (Even the title of the study should give you pause; you don’t do a study to justify the use of a drug you’ve already decided to use. What if the results of the study indicated the opposite? An objective scientific study wouldn’t know the results in advance.)

Anyway, on to the study, about which there’s much to dislike and critique—for example, everything.

The JUPITER trial looked at nearly eighteen thousand people whose cholesterol was perfectly normal or even on the low side. What these folks did have, however, were elevated levels of C-reactive protein (CRP). As we’ve said, CRP is a general measure of inflammation, and for the record, it’s a measure we consider important. (You’ll read more about CRP testing in
chapter 9
.) Now it’s abundantly clear that what the manufacturers of the drug were aiming for here was a demonstration that statin drugs help prevent deaths even in people with normal cholesterol!

So here’s the party line on the JUPITER trial, the line that was robotically repeated in virtually every news outlet in America: The JUPITER trial was such a resounding success that they had to stop it early because it would be “unethical” to continue, given that the group being treated with the drug (Crestor) experienced half as many deaths, strokes, and heart attacks as the control (untreated) group.

The JUPITER trial was touted everywhere as proof that the cholesterol guidelines needed to be changed. Clearly, the drug manufacturers argued, people who met or exceeded the existing standards for cholesterol were demonstrably helped by lowering their “normal”
cholesterol even further, virtually cutting their risk for all kinds of terrible things in half! Obviously, they argued to anyone who would listen, we need to make the recommended “normal” levels even lower! (Can you imagine the cheers that would erupt at stockholders’ meetings if your product just expanded its market by roughly eleven million people?
³⁰
Why that’s almost as good as expanding an adult market by targeting children! Oh, that’s right. As of 2011, that’s what the statin lobbyists were doing. Never mind.)
*

Well that was then. This is now.

Nine respected authors, including a Harvard Medical School faculty member, teamed up to write a critical reappraisal of the JUPITER trial, a reappraisal that was published in 2010 in
Archives of Internal Medicine
, one of the most respected, and conservative, medical journals in the world.
³¹
“The trial was flawed,” they wrote. “It was discontinued (according to pre-specified rules) after fewer than two years of follow-up, with no differences between the two groups on the most objective criteria.” The authors also said, “The possibility that bias entered the trial is particularly concerning because of the strong commercial interest in the study.” They concluded that “[t]he results of the trial do not support the use of statin treatment for primary prevention of cardiovascular diseases.”

So how did this study manage to garner headlines like this one: “Heart Attack Risk Lowered More Than 50 Percent by Taking Crestor!”?

Let’s take a look.

The JUPITER trial took 17,800 people—men over sixty, women over fifty—and put them into two groups. One group received 20 mg of Crestor daily, while the other group received a placebo.

Now before we tell you the results, let’s recall the distinction between relative versus absolute numbers, a distinction we talked about earlier.

The study went on for 1.9 years, and at the end of that time it was determined that the risk of having a heart attack in the placebo group was 1.8 percent, while the risk of having a heart attack in the Crestor group was 0.9 percent.

So, yes, there was a 50 percent reduction in risk! Relatively speaking. But let’s do the math on the number that really matters, the absolute risk.

The placebo group had a 1.8 percent risk, and the Crestor group had a 0.9 percent risk, so the absolute, real reduction in risk was 1.8 minus 0.9, or 0.9 percent. In absolute numbers, this means that if you took a group of 100 untreated people, 1.8 of them would have a heart attack at some point over the course of almost two years. If you took that same group of 100 people and treated them all with Crestor for the same period, 0.9 of them would have a heart attack. Researchers calculate that this translates into 120 people needing treatment for 1.9 years in order to prevent one event. At a cost of well over a quarter of a million dollars for almost two years’ worth of Crestor, that’s an awful lot to spend to prevent one event. Especially when there’s a significant chance of experiencing really bad side effects from the medicine that’s costing you a fortune.

Commenting on the JUPITER study in the
New England Journal of Medicine
in November 2008, Mark A. Hlatky, M.D., wrote: “[A]bsolute differences in risk are
more clinically important than relative reductions in risk in deciding whether to recommend drug therapy, since the absolute benefits of treatment must be large enough to justify the associated risks and costs.” He added that “[l]ong-term safety is clearly important in considering committing low-risk subjects without clinical disease to twenty years or more of drug treatment.”
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Did we mention that there was a significantly higher incidence of diabetes in the group treated with Crestor?
³³
(In her studies on statin side effects, Stephanie Seneff also observed a highly significant correlation—p = 0.006—between mentions of diabetes and statin drug side effect reports.)

Now, if you’re still on the cholesterol-lowering/statin bandwagon, you might be forgiven for trying to look on the bright side. “Look,” we can almost hear you saying, “maybe you guys are right. Maybe lowering cholesterol
doesn’t matter all that much. But clearly there are some good things statins do besides lower cholesterol, as you yourselves have pointed out. They’re anti-inflammatory, they’re powerful anti-oxidants, and they thin the blood. So what’s the harm if people take them?”

Statins are being prescribed left and right to people who have absolutely no business being on them, and to populations for which they have shown no real benefit.

Fair enough. For some people, especially middle-aged men who’ve already had a first heart attack, the good statins do may indeed outweigh the risks. The problem is twofold: One, statins are being prescribed left and right to people who have absolutely no business being on them, and to populations for which they have shown no real benefit. Two, the risks are significant, serious, varied, and highly underpublicized.

Before we get to our evaluation of the risks and benefits of statin drugs, let’s review exactly what it is that cholesterol does in the first place. Understanding the functions of this much maligned molecule will help you understand why so many things can go wrong when we pursue lower and lower cholesterol numbers.