To determine if supplements of vitamin C, vitamin E, beta-carotene, and B-vitamins (folic acid, vitamins B6 and B12) reduce risk of major cardiovascular events in high risk women with a prior history of atherosclerotic cardiovascular disease. The trial is a companion to the Women's Health Study (WHS), a primary prevention trial of vitamin E and aspirin in a low risk population of women.

Study Type: Interventional

Study Design: Prevention, Randomized, Placebo Control, Factorial Assignment

Study Primary Completion Date: February 2006

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.

Folic acid, vitamin B6, vitamin B12 are involved in homocysteine metabolism and are also postulated to have cardioprotective effects. 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 hypotheses.

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. In 1998, participants were further randomized to the B-vitamin intervention (folic acid, vitamin B6, vitamin B12).

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 and include all major cardiovascular events such as non-fatal myocardial infarction, non-fatal stroke, coronary revascularization procedures, 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 will continue until February 2006.

Intervention(s) in this Clinical Trial

• Behavioral: dietary supplements
• Drug: vitamin C
• Drug: vitamin E
• Drug: beta-carotene
• Drug: folic acid/Vitamin B6/Vitamin B12

• Women, aged 40 and over, at high risk, with a history of coronary artery disease, carotid endarterectomy, peripheral artery surgery, or three or more coronary heart disease risk factors.

Gender Eligibility for this Clinical Trial: Female

Minimum Age for this Clinical Trial: 40 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: National Heart, Lung, and Blood Institute (NHLBI)

Overall Clinical Trial Officials and Contacts

JoAnn Manson  Brigham and Women's Hospital  

Information obtained from ClinicalTrials.gov on August 28, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00000541

Study ID Number: 84

ClinicalTrials.gov Identifier: NCT00000541

Health Authority: United States: Federal Government