Overdosed America (22 page)

The drug companies have plenty to gain from the pro-drug orientation of the updated guidelines. If the guidelines are followed, sales of cholesterol-lowering statin drugs will increase by at least $20 billion to $30 billion per year. (The total cost will be even more because of the extra doctor visits and blood tests necessary to make sure that the drugs are not causing side effects such as inflammation of the liver or breakdown of muscle tissue.) Of course, experts’ financial ties to corporations do not necessarily mean that the report itself is biased by corporate influence. A close comparison of the data and recommendations presented in the guidelines to the available scientific evidence speaks for itself.

Two of the five major studies incorporated into the new guidelines tested the effectiveness of statin therapy in the primary prevention of coronary heart disease. One was the West of Scotland Coronary Prevention Study (WOSCOPS), published in the
New England Journal of Medicine
in 1995. Western Scotland has one of the highest rates of heart disease in the world, and the 6600 men included in the WOSCOPS study were at particularly high risk: their average LDL cholesterol level was 192 mg/dL; 44 percent of them smoked; and, though men with a history of heart attack were excluded from the study, one out of five had symptoms of blocked arteries, such as angina or leg pain with exertion. The men were randomly assigned to receive either a statin drug, Pravachol 40 mg per day, or a placebo.

After almost five years, the men who took Pravachol had 31 percent fewer heart attacks (statistically significant) and 22 percent fewer deaths (not quite statistically significant) than the men in the control group. More relevant than these large reductions in relative risk in determining the real benefit of treating these very high risk men with Pravachol is the actual number of heart attacks and deaths prevented. This turns out to be a much less impressive number: 100 men in the study had to take Pravachol for two full years in order to prevent a single heart attack.
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The cost of treating 100 people for two years with Pravachol 40 mg per day was $336,000 (for the drugs alone). In order to prevent a single death, 100 men in the WOSCOPS study would have had to take Pravachol for five and a half years.

Of course, when I was in practice, I wanted to protect my very high risk patients from suffering a heart attack, and recommended they take a statin. At the same time, it is important to remember that even among the highest-risk men without coronary heart disease, 99 out of every 100 would take Pravachol for two years without any benefit. The problem is that we can’t know in advance who the hundredth man is going to be, and for that individual the protection conferred by the statin drug is very important.

In contrast to the very high risk men in the WOSCOPS study, the other major study of primary prevention, the
Air Force/Texas Coronary Atherosclerosis Prevention Study
(AFCAPS/TexCAPS), included people with only a moderately elevated risk of developing heart disease. Researchers randomly assigned 6600 healthy middle-aged and older people with mildly elevated LDL cholesterol and below-normal HDL cholesterol levels
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to be treated with lovastatin (brand name Mevacor) or a placebo for five years. The study then compared the frequency of several health outcomes in the two groups: occurrence of coronary heart disease, any serious disease, death from coronary heart disease, and death from any cause. The guidelines summarize the results: “AFCAPS/TexCAPS is important because it showed that LDL-lowering therapy in persons with only borderline-high LDL-cholesterol levels produces a large reduction in relative risk.”

Well, sort of. The report neglected to specify the relative risk of what, exactly, the statin reduced. The relative risk of developing coronary heart disease was indeed significantly lower (37 percent) in the people who took the statin compared with those who took placebos. However, the guidelines failed to disclose an even more important measure of the impact of treatment with a statin, a finding that was reported in the original article published in JAMA in 1998. The risk of developing any serious disease (the kind of illness that requires hospitalization or that causes death) was identical in the people who took the statin and those who took the placebo. The new guidelines report that the effect of statin treatment on the overall risk of death in the AFCAPS/TexCAPS study was inconclusive. Not so. A definitive conclusion can be drawn: In a five-year study involving 6600 people with moderately elevated LDL cholesterol levels, treatment with a statin did not decrease overall mortality. In fact, a few more of the people who took the statin died (80) than those who took the placebo (77).

In other words, the net result of treating people with moderate risk of developing coronary artery disease with a statin was simply to trade coronary heart disease for other serious diseases, with no overall improvement in health.

Disregarding, for the moment, the fact that statins had no effect on the overall risk of serious illness or death, even the “large reduction in relative risk” of developing coronary heart disease touted in the guidelines translates into a much less impressive reduction in absolute risk. One hundred people in this study would have to be treated with a statin drug for two and a half years to prevent a single episode of heart disease—and the other 99 people would not have derived any benefit. In order to prevent one death from cardiovascular disease, 100 people in this study would have to have been treated with a statin drug for
25
years.
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The updated guidelines relied heavily on AFCAPS/TexCAPS to develop the two-step risk-assessment process that doctors now use to determine which patients should take statins. A look at how those criteria actually apply to the men in this study, however, reveals a paradoxical result.
At least 85 percent of the men
are in the risk category for which the executive summary of the guidelines states, “Use of LDL-lowering drugs at this risk level reduces CHD risk and is cost-effective.”

Notwithstanding the lack of overall health benefits in the people who received statin therapy in AFCAPS/TexCAPS, the guidelines later contradict their own recommendation, concluding that the
“incremental cost per additional year
of life gained would be >$100,000 for the whole cohort of AFCAPS/TexCAPS,” and that this is too expensive to justify statin treatment. In other words, if you do the arithmetic, the guidelines recommend statin therapy for everyone who has a health profile similar to 85 percent of the men in AFCAPS/TexCAPS. But the report then goes on to say that the cost would be prohibitive. And notwithstanding this internal contradiction, it is simply nonsensical (or perhaps a diversion) to even contemplate how much each year of life gained in AFCAPS/TexCAPS would cost, because the overall death rate was
higher,
not lower, in the people who took a statin drug.

The bottom line is that these two studies show that men who do not have CHD but do have very high cholesterol levels might benefit from taking a statin drug, though not nearly as much as all the talk of “miracle drugs” leads us to believe. The case for prescribing statins for men with only moderately elevated cholesterol levels is far less compelling.

The updated guidelines are definitive: “In recent trials,
statin therapy reduced risk for CHD in . . . women
, in those with or without heart disease.” The
NCEP’s full report convincingly cites six references
to back up this statement.

None of the six references cited, however, provides significant evidence to back up the claim that statin therapy reduces the risk of CHD in women without heart disease: three apply to people who already have heart disease; one is the WOSCOPS study, which included no women; one is AFCAPS/TexCAPS, in which there were only a total of 20 episodes of heart disease among the women in the study—not nearly enough to reach statistical significance; and one was a compilation of five other studies. A review article published in JAMA in 1995 concluded:
“There is no evidence from primary prevention trials
that cholesterol lowering affects total mortality in healthy women.”

It is hard to believe that the only evidence from randomized controlled (gold standard) studies that addresses the primary prevention of heart disease in women with statins consists of these statistically inconclusive 20 episodes of coronary heart disease, which are being used to justify putting millions of healthy women on statins. This fact is not disputed in the guidelines, which later state under the heading
“Special Considerations for Cholesterol Management in Women (Ages 45–75)”
:
“Clinical trials of LDL lowering generally are lacking for this risk category; rationale for therapy is based on extrapolation of benefit from men of similar risk” (
italics mine
)
.

The cholesterol guidelines’ cavalier extrapolation to women of the benefit of lowering cholesterol in men, especially after the recent surprise provided by the results of the “Heart and Estrogen/Progesterone Replacement Study” (HERS study),
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demonstrates the medical industry’s unrepentant opportunism in its attempt once again to impose scientifically unsubstantiated medical treatment on women. Such a sweeping recommendation, without unimpeachable evidence from the gold standard of at least one large randomized clinical trial, and optimally several such trials, makes a travesty of the claim that American medicine upholds its standards of excellence by adhering strictly to scientific evidence.

The guidelines are very enthusiastic about the prospects for reducing heart disease in people age 65 and older who have an increased risk of, but have not yet developed, coronary heart disease. Specifically for this group, the report states that recent trials have shown
“aggressive LDL-lowering therapy
[meaning with a statin drug] is effective in reducing CHD (see Table II.2-3).”
The table cites nine references
to support this strong claim.

Checking each reference produced the same results as checking the references that supposedly showed that women without heart disease benefit from statin therapy: only one of the nine references (AFCAPS/TexCAPS) is at all relevant to primary prevention of CHD in the elderly, and even in this study only one-fifth of the people involved had reached the age of 65, and the reduction in their risk of heart disease was not statistically significant.

What about the other studies? Six were of secondary prevention (people who are at much higher risk because they already have CHD); two were of primary prevention, but one of these did not include patients over the age of 64, and the other was published in 1978, long before statins were available, and the
average age was 51
. So, the nine references notwithstanding, no significant evidence from randomized controlled trials has been presented to support this recommendation.

The guidelines also refer to population-based (epidemiological) data to justify the increased use of statins:
“The relationship between serum cholesterol
levels and lifetime risk for CHD has been evaluated in the Framingham Heart Study.. . . Even at age 70 the lifetime risk for CHD remains high.” Though both halves of this statement are true independently, their juxtaposition could easily lead the reader to draw the wrong conclusion.

Of course the lifetime risk for CHD is high once the age of 70 is reached; eventually hearts give out in people lucky enough to reach a ripe old age and otherwise in good health. And it’s true that the Framingham study examined the relationship between increased cholesterol levels and the risk of heart disease at different ages. But, as mentioned before, the data showed exactly the opposite of what the guidelines imply:
total cholesterol is not significantly related to mortality
from coronary heart disease beyond the age of 60. Indeed, the authors of the paper, based on data from the Framingham Heart Study, warned: “Physicians should be cautious about initiating cholesterol-lowering treatment in men and women above 65 to 70 years of age. Only randomized clinical trials in older people can settle the debate over the efficacy and cost-effectiveness of lipid-lowering interventions for reducing mortality and morbidity in this population.” At the time the updated guidelines were published, no such studies had been reported. Furthermore, a study published in the
Archives of Internal Medicine
in 1999 and referenced by the guidelines showed that “None of the lipid measures (total, high-density lipoprotein, and low-density lipoprotein cholesterol or triglycerides) was associated with the risk of MI [myocardial infarction] in this population [of people aged 65 and older].” In other words, there is
not even an increase in the risk of heart attack
associated with higher cholesterol levels once the age of 65 is reached.

The guidelines then rely on two assumptions that make statins appear very effective in the primary prevention of CHD in people who have reached the age of 65. The first is that statin therapy reduces the risk of coronary heart disease in people between the ages of 65 and 80 “by approximately one-third.” The only problem is that none of the nine references cited to justify this assumption provides any significant evidence of benefit from statin therapy after the age of 65 is reached.

The second assumption is that in the elderly, the risk of coronary heart disease increases with increasing cholesterol levels. The article cited to justify this assumption does indeed show that the risk of developing coronary heart disease
remains high in the elderly
, but the article does not examine the relationship between cholesterol levels and the risk of developing CHD.

As we will see at the end of the chapter, when a randomized controlled study of the effect of statins in elderly patients without heart disease was published in 2002, the overreaching estimates of the benefits of statin therapy for people in this age group were not borne out.