Randomised trial of α-tocopherol and β-carotene supplements on incidence of major coronary events in men with previous myocardial infarction

Epidemiological data suggest that the intake of antioxidants such as α-tocopherol (vitamin E) and β-carotene has an inverse correlation with the incidence of coronary heart disease. The results from clinical trials of antioxidant supplementation in people with known coronary heart disease are inconclusive. We studied the frequency of major coronary events in 1862 men enrolled in the Alpha-tocopherol Beta-carotene Cancer Prevention Study (smokers aged between 50 and 69 years) who had a previous myocardial infarction. In this randomised, double-blind, placebo-controlled study, men had received dietary supplements of α-tocopherol (50 mg/day), β-carotene (20 mg/day), both, or placebo. The median follow-up was 5·3 years. The endpoint of this substudy was the first major coronary event after randomisation. Analyses were by intention to treat. 424 major coronary events (non-fatal myocardial infarction and fatal coronary heart disease) occurred during follow-up. There were no significant differences in the number of major coronary events between any supplementation group and the placebo group (α-tocopherol 94/466; β-carotene 113/461; α-tocopherol and β-carotene 123/497; placebo 94/438 [log-rank test, p=0·25]). There were significantly more deaths from fatal coronary heart disease in the β-carotene (74/461, multivariate-adjusted relative risk 1·75 [95% Cl 1·16–2·64], p=0·007) and combined α-tocopherol and β-carotene groups (67/497, relative risk 1·58 [1·05–2·40], p=0·03) than in the placebo group (39/438), but there was no significant increase in the α-tocopherol supplementation group (54/466, relative risk 1·33 [0·86–2·05], p=0·20). The proportion of major coronary events in men with a previous myocardial infarction who smoke was not decreased with either α-tocopherol or β-carotene supplements. In fact, the risk of fatal coronary heart disease increased in the groups that received either β-carotene or the combination of α-tocopherol and β-carotene; there was a non-significant trend of increased deaths in the α-tocopherol group. We do not recommend the use of α-tocopherol or β-carotene supplements in this group of patients.