To determine if supplements of vitamin C, vitamin E, and beta-carotene reduce all major cardiovascular events in high risk women with a prior history of atherosclerotic cardiovascular disease. The trial is piggybacked on the Women's Health Study (WHS), a primary prevention trial of vitamin Eand aspirin in a low risk population of women.

BACKGROUND: The antioxidant properties of vitamin C, vitamin E, and beta-carotene are well known and are postulated to prevent lipoprotein oxidation and thereby prevent or retard atherogenesis. Based on the successful experience with the Physicians' Health Study, the results of a pilot study conducted in nurses, and long-term experience following a large cohort of United States nurses, the study should provide either definitive positive or informative null results regarding the study hypothesis.

DESIGN NARRATIVE: Subjects were randomized in a 2 x 2 x 2 factorial design to 500 mg of vitamin C or placebo daily, 600 mg of vitamin E or placebo on alternate days and/or 50 mg of beta-carotene or placebo on alternate days. There was a three month run-in phase in which eligible patients received placebo caplets. Subjects were randomized only if they reported good compliance, willingness to continue in the trial, had no history of cancer, active liver disease, or use of coumadin, and expressed continued willingness to forego the use of beta-carotene and vitamin A, C, or E supplements. Baseline dietary assessments were made using food frequency questionnaires and information was obtained on aspirin and postmenopausal hormone use at entry and during followup. Subjects were randomized with a stratification by age into eight five-year increments, one being 75+. Endpoints are followed by mail for four years and include all major cardiovascular events such as non-fatal myocardial infarction, non-fatal stroke, a coronary revascularization procedure, and cardiovascular mortality. The trial is conducted as a companion to the Women's Health Study (WHS), a large randomized trial assessing the efficacy of low-dose aspirin and vitamin E in the primary prevention of cardiovascular disease and cancer among apparently healthy women.

The trial is currently in treatment and follow-up which continues till February 2006. Starting in May 1998 the protocol was modified to include a folate B6/B12 arm.

Ages Eligible for Study:  40 Years and above,  Genders Eligible for Study:  Female

Criteria