BACKGROUND: Observational and experimental studies suggest that the amount of 
vitamin E ingested in food and in supplements is associated with a lower risk of 
coronary heart disease and atherosclerosis.
METHODS: We enrolled a total of 2545 women and 6996 men 55 years of age or older 
who were at high risk for cardiovascular events because they had cardiovascular 
disease or diabetes in addition to one other risk factor. These patients were 
randomly assigned according to a two-by-two factorial design to receive either 
400 IU of vitamin E daily from natural sources or matching placebo and either an 
angiotensin-converting-enzyme inhibitor (ramipril) or matching placebo for a 
mean of 4.5 years (the results of the comparison of ramipril and placebo are 
reported in a companion article). The primary outcome was a composite of 
myocardial infarction, stroke, and death from cardiovascular causes. The 
secondary outcomes included unstable angina, congestive heart failure, 
revascularization or amputation, death from any cause, complications of 
diabetes, and cancer.
RESULTS: A total of 772 of the 4761 patients assigned to vitamin E (16.2 
percent) and 739 of the 4780 assigned to placebo (15.5 percent) had a primary 
outcome event (relative risk, 1.05; 95 percent confidence interval, 0.95 to 
1.16; P=0.33). There were no significant differences in the numbers of deaths 
from cardiovascular causes (342 of those assigned to vitamin E vs. 328 of those 
assigned to placebo; relative risk, 1.05; 95 percent confidence interval, 0.90 
to 1.22), myocardial infarction (532 vs. 524; relative risk, 1.02; 95 percent 
confidence interval, 0.90 to 1.15), or stroke (209 vs. 180; relative risk, 1.17; 
95 percent confidence interval, 0.95 to 1.42). There were also no significant 
differences in the incidence of secondary cardiovascular outcomes or in death 
from any cause. There were no significant adverse effects of vitamin E.
CONCLUSIONS: In patients at high risk for cardiovascular events, treatment with 
vitamin E for a mean of 4.5 years had no apparent effect on cardiovascular 
outcomes.