PREVENTION OF CORONARY HEART DISEASE BY DRUGS, BUT NOT BY VITAMINS

(April 2003)

The risk of coronary heart disease and heart attacks is increased by elevated blood levels of cholesterol (or its dangerous component, low-density lipoprotein cholesterol - LDL), and by low levels of high-density lipoprotein cholesterol (HDL, good cholesterol). Antioxidants are thought by some to be protective, particularly vitamins E and C and beta carotene. A very good study in The New England Journal of Medicine examined those factors that increase or decrease risk.

One hundred sixty men and women with known coronary heart disease were assigned to one of four regimens: a drug to lower cholesterol levels (a powerful statin - in this case, simvastatin, trade name Zocor) plus niacin to raise HDL levels; antioxidants (vitamins E, C, beta carotene, selenium); both; neither. The measured endpoint was narrowing of the coronary blood vessels over a three-year period determined by direct visualization of the coronary blood vessels by an invasive technique called angiography.

The results with the cholesterol-lowering statin and the HDL raising niacin were impressive. The LDL concentrations decreased markedly, the HDL increased substantially, and, over the next few years, the narrowing of the coronary vessels actually lessened and only 3 percent of the patients developed a coronary event such as heart attack.

The results with the antioxidants were unimpressive. Although only one-half as much progression of coronary vessel narrowing was found compared to the controls (who received only an inactive placebo), the differences were not statistically significant and there were more than 20 percent new coronary events, identical to the controls.

The results with the combination of statin-niacin-antioxidants were intriguing. The antioxidants actually interfered somewhat with the beneficial effects of the statin plus niacin. Instead of lessened narrowing, there was a small amount of increased blood vessel narrowing, though not nearly as much as seen with the controls or the antioxidants alone. Similarly, the occurrence of heart attack events during followup in the statin-niacin-antioxidants group was greater than in the statin-niacin group, and actually was midway between the statin-niacin group and the controls (or the antioxidants alone).

The authors concluded that the statin-niacin combination was very effective in preventing progression of coronary heart disease and heart attacks, but "the use of antioxidant vitamins in this setting must be questioned".

Commentary: This is a very interesting report. However, the roles of the two drugs may not be quite as separate as the report suggest. The statin lowered the LDL (bad cholesterol), but it also may have played some role in raising the HDL. On the other hand, the niacin acted, in large part, by raising the HDL; all the participants in the study at the start had low blood HDL levels. But, niacin, which was given in huge doses (2,000 milligrams a day as contrasted with a standard multivitamin dosage of 20 milligrams) can also lower LDL. At that huge dosage, it often has unpleasant side reactions that may make it difficult to keep taking it.

The lack of effectiveness of the antioxidants alone is not surprising - vitamin C and beta carotene have never looked impressive in prevention of coronary heart disease and multiple recent studies on vitamin E in preventing progression have been discouraging. Selenium is a trace element. Its role in preventing the onset or progression of coronary heart disease has never been adequately documented. But, the interference with the benefits of the statin-niacin combination was unexpected. The authors believe it resulted from reduction in the HDL raising effect that was primarily due to the niacin. Obviously, it is impossible to tell which of the four antioxidants was responsible for the interference; it could have been one of the agents or any combination.

for the benefit of marked lowering of cholesterol (and of LDL) by powerful statins (such as Zocor, Pravachol, Lipitor) and the benefit of raising HDL levels. It is often hard to raise HDL levels; stopping smoking, exercise, weight loss, and a drink or two a day may help, but the increase if it occurs at all, it is usually very modest. The statins and a drug called Gemfibrozil are often somewhat effective, but niacin in very large doses is clearly the best; however, side reactions, particularly episodes of flushing, warmth, and redness, can be quite unpleasant.

or even

for the ability of any vitamin (other than folic acid and huge doses of niacin) to either prevent the occurrence of heart attacks or slow the progression of coronary heart disease.

Brown, B.G., et al. Simvastatin and niacin, antioxidant vitamins or the combination for the prevention of coronary disease. The New England Journal of Medicine. Vol 345 (November 29) Pgs 1587-1592. 2001.