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Women's Health Study: Vitamin E in Primary Prevention - Women's Health Study: Vitamin E in Primary Prevention
Description:
The goal of the trial was to evaluate treatment with vitamin E for the primary prevention of cardiovascular disease in women.
Hypothesis:
Treatment with vitamin E compared with placebo will be associated with a reduction in primary cardiovascular events in women.
Study Design
Patients Enrolled: 39,876
Mean Follow Up: Mean 10.1 years
Mean Patient Age: Mean age 55
Female: 100
Patient Populations:
Age ≥45 years; no history of coronary heart disease, cerebrovascular disease, cancer (except nonmelanoma skin cancer), or other major chronic illness; no history of side effects to any of the study medications; not taking aspirin or nonsteroidal anti-inflammatory medications more than once a week (or were willing to forego their use during the trial); not taking anticoagulants or corticosteroids; and not taking individual supplements of vitamin A, E, or beta carotene more than once a week
Primary Endpoints:
Risk of vascular events (combined endpoint of nonfatal MI, nonfatal stroke, and total cardiovascular death) and incidence of total malignant neoplasms of epithelial cell origin
Drug/Procedures Used:
Healthy female health professionals over age 45 participating in the study were randomized to treatment with vitamin E (n=19,937; 600 IU on alternate days) or placebo (n=19,939). Women were also randomized in a factorial design to treatment with low-dose aspirin or placebo. Participants were treated and followed for a mean of 10.1 years. Participants were followed for the occurrence of nonfatal myocardial infarction (MI), nonfatal stroke, and cardiovascular death. Events were reviewed by an Endpoints Committee of physicians who were blinded to treatment assignment.
Principal Findings:
The primary composite endpoint of major cardiovascular events occurred in 482 women in the vitamin E group and 517 in the placebo group (relative risk [RR] 0.93, 95% confidence interval [CI] 0.82-1.05, p=0.26). Among the individual components of the composite endpoint, there was no difference in MI (n=196 vs. n=195, RR 1.01, p=0.96), either fatal or nonfatal. There was also no difference in total stroke (n=241 for vitamin E vs. n=246 for placebo, RR 0.98, p=0.82), ischemic stroke (n=194 vs. n=197, RR 0.99, p=0.88), or hemorrhagic stroke (n=44 vs. n=48, RR 0.92, p=0.68) or fatal or nonfatal stroke. Death from cardiovascular causes was significantly lower in the vitamin E group (n=106 vs. n=140, RR 0.76, 95% CI 0.59-0.98, p=0.03), while there was no difference in all-cause mortality (n=636 vs. n=615, RR 1.04, p=0.53). In subgroup analysis, there was no modification of the primary endpoint results among women with a high level of compliance, women using hormone replacement therapy, or by menopausal status.
Side effects did not differ between the two randomized groups, with a gastrointestinal bleed rate of 4.2% in the vitamin E group and 4.1% in the placebo group (p=0.77). There was no difference by treatment group in total cancer (RR 1.01, p=0.87), breast cancer (RR 1.00, p=0.95), lung cancer (RR 1.09, p=0.52) or colorectal cancer (RR 1.00, p=0.99).
Interpretation:
Among initially healthy women, treatment with vitamin E was not associated with a difference in the primary endpoint of major cardiovascular event reduction compared with placebo at a mean 10-year follow-up.
Following initial promise for vitamin E in observational epidemiologic studies, randomized trials of vitamin E for secondary prevention did not demonstrate benefit, as shown in the large Heart Protection Study. These findings, along with data from the earlier Heart Protection Study, do not support use of vitamin E for prevention of cardiovascular disease.
In the present study, the reduction in cardiovascular death associated with vitamin E use will require further exploration, as there was no decrease in fatal MI or fatal stroke. The cardiovascular mortality reduction was primarily due to a reduction in sudden death.
References:
Lee IM, et al. Vitamin E in the Primary Prevention of Cardiovascular Disease and Cancer. JAMA. 2005;294:56-65.
Presented by Dr. Julie E. Buring at the March 2005 ACC Annual Scientific Session, Orlando, FL.
Keywords: Risk, Myocardial Infarction, Stroke, Skin Neoplasms, Follow-Up Studies, Vitamin E, Chronic Disease, beta Carotene, Death, Sudden, Breast Neoplasms, Coronary Disease, Primary Prevention, Vitamins, Secondary Prevention, alpha-Tocopherol, Vitamin A, Colorectal Neoplasms, Confidence Intervals, Hormone Replacement Therapy, Lung Neoplasms
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