BACKGROUND: Epidemiological data suggest that the intake of antioxidants such as 
alpha-tocopherol (vitamin E) and beta-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.
METHODS: 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 alpha-tocopherol (50 mg/day), beta-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.
FINDINGS: 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 (alpha-tocopherol 94/466; beta-carotene 113/461; 
alpha-tocopherol and beta-carotene 123/497; placebo 94/438 [log-rank test, p = 
0.25]). There were significantly more deaths from fatal coronary heart disease 
in the beta-carotene (74/461, multivariate-adjusted relative risk 1.75 [95% CI 
1.16-2.64], p = 0.007) and combined alpha-tocopherol and beta-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 alpha-tocopherol 
supplementation group (54/466, relative risk 1.33 [0.86-2.05], p = 0.20).
INTERPRETATION: The proportion of major coronary events in men with a previous 
myocardial infarction who smoke was not decreased with either alpha-tocopherol 
or beta-carotene supplements. In fact, the risk of fatal coronary heart disease 
increased in the groups that received either beta-carotene or the combination of 
alpha-tocopherol and beta-carotene; there was a non-significant trend of 
increased deaths in the alpha-tocopherol group. We do not recommend the use of 
alpha-tocopherol or beta-carotene supplements in this group of patients.