Antioxidants Don't Reduce Risk of MI, Stroke, or Cardiovascular Death in High-Risk Women

BOSTON, Aug. 14 -- Antioxidant vitamins C and E and beta carotene did not reduce the risk of cardiovascular events in more than 8,000 high-risk women, reported researchers here.

Neither Vitamin C (ascorbic acid), vitamin E, or beta carotene reduced the combined primary end point of myocardial infarction, stroke, coronary revascularization, or cardiovascular death, reported Nancy R. Cook, Sc.D., of Brigham and Women's Hospital and Harvard, and colleagues in the Aug. 13/27 issue of Archives of Internal Medicine.

"For stroke, we found a significant 2-way interaction between ascorbic acid and vitamin E (P =0.03). Those in the active groups for both agents experienced fewer strokes compared with those in placebo groups for both agents (RR 0.69; 95% CI 0.49-0.98 [P =0.04])," they wrote.

And, they noted, there was also "a marginally significant reduction in the primary outcome with active vitamin E among a prespecified group of women with [cardiovascular disease] (RR, 0.89; 95% CI, 0.79-1.00, P =0.04)."

The Women's Antioxidant Cardiovascular Study recruited 8,171 women, average age 61, in 1995 and 1996. All participants had a history of cardiovascular disease or had at least three risk factors for it.

Women were randomized to 500 mg of vitamin C or placebo daily, 500 IU of vitamin E or placebo every other day, and 50 mg of beta carotene or placebo every other day. The study design allowed researchers to assess the efficacy of the vitamins as monotherapy or in combination with other antioxidants.

The women were followed for a mean of 9.4 years during which time 1,450 women had one or more cardiovascular events-274 myocardial infarctions, 298 strokes, and 889 coronary revascularization procedures. There were 995 deaths, 395 of which were from cardiovascular causes.

No additional adverse effects were observed among those taking the vitamins, although there was a small increase in reports of upset stomach among those taking active beta carotene.

Limitations of the study noted by the authors included a lack of complete follow-up and compliance, although, they said, it was above 90% through 2003. Mortality follow-up was 99% complete and compliance was comparable to other trials.

"While additional research into combinations of agents, particularly for stroke, may be of interest, widespread use of these individual agents for cardiovascular protection does not appear warranted," the researchers concluded.