63 other researchers. Three of the co-workers came from the drug company Bristol-Myers Squibb, the makers of the trial drug.
After six years, total mortality was lowered significantly-by 14 per cent in the controls compared with 11 per cent in the treatment group. CHD mortality was lowered by 8.3 per cent in the controls and by 6.2 per cent in the treatment group. These effects were again more pronounced in men. In fact, the benefit to women
was much lower and not statistically significant.
In addition, although an effect was seen regardless of
the initial total or low-density lipoprotein (LDL) cholesterol levels, the effect in patients with LDL cholesterol levels below 135 mg/dL was not
statistically significant (N Engl
J Med, 1998; 339: 1349-57).
The wrong culprit
In their reports, the directors
of these trials cited LDL chol-esterol as an important risk
factor in CHD. But what these trials actually provide, in spite of the glowing reports they re-ceived in the press, is strong evidence that cholesterol levels do not matter.
In some trials, the statins were almost as effective in women as they were in men. Indeed, in the CARE trial (see box on p 4), the effects were more pronounced in the fe-male sex, although almost all studies have shown that high cholesterol is not a risk factor
Second, the elderly were protected as much as younger individuals, although all studies have shown that high cho-lesterol is only a weak risk factor, if at all, in men over 50.
Third, the number of strokes was reduced after statin treatment, although all studies have shown that high cholesterol is, at best, a weak risk factor for stroke.
Fourth, patients who had suffered a heart attack were protected, even though most studies have shown that high cholesterol is a weak risk factor, if at all, in those who have already had a heart attack (Am J Med Sci, 1964; 247: 145-55).
Furthermore, the statins protected against CHD whe-ther cholesterol was high or low, even though most studies have shown that normal or low cholesterol is not a risk factor for CHD.
Most important, there was no association between the degree of cholesterol lowering and the outcome. The risk of having a heart attack was reduced by the same degree regardless of whether the cholesterol level was lowered by a large or small amount.
This phenomenon is called 'lack of exposure response' and is a strong indication that the factor under investigation is not the true cause, but secondary to the real cause.
So, why are the statins effective in individuals for whom cholesterol is not a risk factor? And why is it that the effect of the statins does not depend on how much they lower blood cholesterol? If the cholesterol level is not a risk factor
for CHD in these people, why should a reduction of that cholesterol improve their chances of avoiding a heart attack? If the level of our blood cholesterol is as important as we have been told it is for so many years, then why doesn't it matter whether we lower it by large or small amounts?
The only reasonable explanation is that the statins do more than just lower cholesterol. There is strong evidence to show exactly that.
The statins inhibit the body's production of a substance called mevalonate, a precursor of cholesterol. When the production of mevalonate goes down, less cholesterol is produced by the cells, and blood cholesterol goes down as well.