After 8 years of treatment, the antioxidant vitamins E and C do not help prevent myocardial infarction (MI), stroke, or cardiovascular (CV) death in low-risk men, according to findings from the Physicians' Health Study II (NCT00270647). These findings refute the belief that long-term treatment with these antioxidant vitamins are cardioprotective, researchers reported.

“Available trial data do not support the use of vitamin E and vitamin C supplements as part of a comprehensive cardiovascular disease prevention strategy,” said J. Michael Gaziano, MD, Brigham and Women's Hospital and VA Medical Center, Boston, MA. Dr. Gaziano presented results of the Physicians' Health Study II, which were simultaneously published online in the Journal of the American Medical Association [Sesso HD et al. JAMA 2008].

In the Physicians' Health Study II, 14,641 male doctors were randomly assigned to receive vitamin E (400 IU every other day) or placebo, and also assigned to receive an additional vitamin C supplement (500 mg/day) or placebo. The participants were relatively healthy when they enrolled in the study, of whom just 5.1% had cardiovascular disease at baseline. The mean age of participants was 64 years at the start of the study, which began in 1997. The primary endpoint was major CV events, which was a composite of nonfatal MI, nonfatal stroke, and CV mortality.

After 8 years of follow-up, there were 1245 confirmed major CV events. A similar number of events were reported in the groups that received vitamin E versus placebo (620 vs 625 events; HR, 1.01; 95% CI, 0.90 to 1.13; p=0.96) and in the groups that received vitamin C versus placebo (619 vs 626 events; HR, 0.99; 95% CI, 0.89 to 1.11; p=0.84).

Treatment with vitamin E was associated with an increased risk of hemorrhagic stroke compared with placebo (39 vs 23 events; HR, 1.74; 95% CI, 1.04 to 2.91; p=0.04). By comparison, vitamin C had no effect on the risk of hemorrhagic stroke (30 vs 32 events; HR, 0.95; 95% CI, 0.57 to 1.56).

Vitamins E and C, alone or in combination, had no effect on any of the other individual endpoints of nonfatal MI, ischemic stroke, CV death, or other CV outcomes. In particular, there was no interaction between vitamin E and congestive heart failure (CHF). The trial investigators designated CHF as a prespecified secondary endpoint, given the suggestion of a relationship between vitamin E and CHF in the HOPE trial.

Data on a third randomization, in which participants received either a daily multivitamin supplement or placebo, are still being evaluated. Researchers also collected information on cancer incidence and will report these findings at a later time, Dr. Gaziano said.