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Jarmo Virtamo, MD, PhD; Janne M. Rapola, MD; Samuli Ripatti, MSc; Olli P. Heinonen, MD, ScD; Philip R. Taylor, MD, ScD; Demetrius Albanes, MD; Jussi K. Huttunen, MD, PhD

Arch Intern Med. 1998;158:668-675.

Background  Oxidized low-density lipoprotein is involved in the pathogenesis of atherosclerosis. In epidemiological studies antioxidants have been inversely related with coronary heart disease. Findings from controlled trials are inconclusive.

Methods  We studied the primary preventive effect of vitamin E (alpha tocopherol) and beta carotene supplementation on major coronary events in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, a controlled trial undertaken primarily to examine the effects of these agents on cancer. A total of 27271 Finnish male smokers aged 50 to 69 years with no history of myocardial infarction were randomly assigned to receive vitamin E (50 mg), beta carotene (20 mg), both agents, or placebo daily for 5 to 8 years (median, 6.1 years). The end point was the first major coronary event, either nonfatal myocardial infarction (surviving at least 28 days; n=1204) or fatal coronary heart disease (n=907).

Results  The incidence of primary major coronary events decreased 4% (95% confidence interval, -12% to 4%) among recipients of vitamin E and increased 1% (95% confidence interval, -7% to 10%) among recipients of beta carotene compared with the respective nonrecipients. Neither agent affected the incidence of nonfatal myocardial infarction. Supplementation with vitamin E decreased the incidence of fatal coronary heart disease by 8% (95% confidence interval, -19% to 5%), but beta carotene had no effect on this end point.

Conclusions  Supplementation with a small dose of vitamin E has only marginal effect on the incidence of fatal coronary heart disease in male smokers with no history of myocardial infarction, but no influence on nonfatal myocardial infarction. Supplementation with beta carotene has no primary preventive effect on major coronary events.

From the National Public Health Institute (Drs Virtamo, Rapola, and Huttunen and Mr Ripatti) and the Department of Public Health, University of Helsinki (Dr Heinonen) Helsinki, Finland; and the National Cancer Institute, Bethesda, Md (Drs Taylor and Albanes).

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