Cardioprotective Benefit of Vitamin E Goes South

OB/GYN News,  March 15, 2000  by Bruce Jancin

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SNOWMASS, COLO. -- It's no longer possible in good conscience to advise patients to take vitamin E to prevent cardiovascular disease, Dr. Robert A. Vogel declared at a conference sponsored by the American College of Cardiology.

Just within the past year, primary and secondary prevention trials involving some 52,000 randomized patients have failed to show that vitamin E has a significant cardioprotective effect, said Dr. Vogel, head of cardiology at the University of Maryland, Baltimore.

Physicians' prejudice that antioxidant vitamins prevent heart disease is based upon a plausible theory coupled with what has turned out to be a "greatly misleading" body of observational data accumulated over a 20-year period in such well-known epidemiologic studies as the Physicians' Health Study and the Nurses' Health Study, he said.

But when the vitamin B hypothesis was put to the test in randomized clinical trials, the three largest trials proved negative. These results have convinced Dr. Vogel: Two years ago, when asked what he as a prominent prevention-oriented cardiologist thought about vitamin E, he recommended taking 400 U daily Now he sees it as nonbeneficial.

The first of the three major negative trials was the Alpha Tocopherol Beta Carotene (ATBC) trial involving 29,000 Finnish smokers. Last year brought the negative 11,324-patient Italian GISSI Prevention trial, followed by the nearly 10,000-patient Heart Outcomes Prevention Evaluation (HOPE) trial.

The attention surrounding the landmark HOPE trial has focused on the impressive reduction in cardiovascular events with ramipril. But the trial had an overshadowed vitamin E arm, in which a nonsignificant 5% increase in cardiovascular events occurred relative to placebo.

The only positive randomized, controlled vitamin E trial was the much smaller Cambridge Heart Antioxidant Study (CHAOS). In this 2,000-patient trial, vitamin E was associated with a sharp reduction in nonfatal MIs. The positive findings remain dogged by troubling questions, including the 17% increase in cardiovascular mortality and 33% rise in total mortality in the vitamin E group (neither reached statistical significance). And the trial failed to show a dose-related response to vitamin E, as would be expected if the antioxidant were truly beneficial, he continued.

It's time for physicians and patients to rearrange their cardiovascular priorities and go with preventive agents that have been shown to work, Dr. Vogel argued.

A wealth of compelling data supports the use of the statins. Four randomized trials, including the GISSI Prevention trial, have shown that fish oil supplements reduce mortality by 20%-60%. One of two aspirin trials has been positive.

Why the marked disparity between observational data and clinical trial outcomes with regard to vitamin E and cardiovascular disease prevention? Dr. Vogel offered a few possible explanations.

It's possible that the oxidative hypothesis of atherosclerosis is simply wrong. Or perhaps vitamin E is effective only in people eating a highly atherogenic diet, as is the norm in the United Kingdom, where CHAOS was conducted. Maybe vitamin E requires rejuvenation via concomitant vitamin C to be an effective antioxidant.

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