Women's Health Study (WHS): A Randomized Trial of Low-dose Aspirin and Vitamin E in the Primary Prevention of Cardiovascular Disease and Cancer
Women's Health Study (WHS): A Randomized Trial of Low-dose Aspirin and Vitamin E in the Primary Prevention of Cardiovascular Disease and Cancer
The purpose of this study is to evaluate the effects of low-dose aspirin and vitamin E in
 primary prevention of cardiovascular disease and cancer in apparently healthy women.
BACKGROUND:

 Various doses of aspirin have been shown to be effective in preventing thrombosis or vascular
 occlusion in several clinical conditions. Short-term studies have documented the efficacy of
 aspirin in preventing occlusion of saphenous vein bypass grants, preventing myocardial
 infarction in patients with unstable angina, preventing transient ischemic attacks and stroke
 in men with cerebral vascular disease, preventing occlusion of injured coronary arteries
 following transluminal angioplasty and aiding in reducing myocardial infarction and total
 mortality in patients receiving fibrinolytic therapy. Additionally, aspirin has been
 effective in the secondary prevention of myocardial infarction in subjects with known
 coronary artery disease. The results of the Physicians' Health Study, a large-scale primary
 prevention trial of aspirin in male physicians, have shown a decrease in myocardial
 infarction, a non-significant increase in cerebral vascular events, and no difference in
 overall mortality. However, few studies have addressed the efficacy of aspirin in vascular
 diseases in women, and it is possible that the risk to benefit ratio may be different in
 women. Specifically, there have been no large primary prevention trials in women, who are at
 risk of coronary heart disease, especially after menopause.

 DESIGN NARRATIVE:

 The Women's Health Study (WHS) is a randomized, double-blind, placebo-controlled trial using
 a 2x2 factorial design. The WHS is sponsored by both NHBLI (HL080467) and NCI (CA047988).
 Approximately 1.75 million female health professionals were contacted by mail to determine if
 they were suitable for inclusion in the study. A three-month run-in phase was performed to
 screen out those with poor compliance. Randomization, which began in February 1993 and ended
 in January 1996, was stratified on five-year age groups. A total of 39,876 participants were
 randomly assigned to either Vitamin E (600 IU every other day) or placebo; and to aspirin
 (100 mg every other day) or placebo. IN the 2x2 factorial design, women were randomly
 assigned to active aspirin and placebo vitamin E (n=9,968), placebo aspirin and active
 vitamin E (n=9,971), active aspirin and active vitamin E (n=9,966), or placebo aspirin and
 placebo vitamin E (n=9,971). A description of the characteristics of women in these 4 groups
 is provided in J Women's Health Gend Based Med 2000;9:19-27. In the main analyses, all women
 on active aspirin (n=19,934) were compared to women on placebo aspirin (n=19,942); and all
 women on active vitamin E (n=19,937) were compared to women on placebo aspirin (n=19,939).

 As part of the initial trial, pre-randomization blood samples from 28,345 participants were
 frozen and stored for genetic analysis which has been supported by non-federal sources.

 The primary endpoint is the reduction of the risk of all important vascular events (a
 combined endpoint of nonfatal myocardial infarction, nonfatal stroke, and total
 cardiovascular death) and a decrease in the incidence of total malignant neoplasms of
 epithelial cell origin. Secondary endpoints are the individual components of the combined
 endpoints. Compliance is measured by replies to a questionnaire sent out every year. The
 trial was completed in 2004 and results were published in 2005 (N Engl J Med
 2005;352:1293-304; JAMA 2005;294:47-55; JAMA 2005;294:56-65).

 Currently, women are being followed on an observational basis.
Inclusion Criteria:

 -  Healthy women

 -  No previous history of cardiovascular disease or cancer

 -  No contraindications to aspirin or vitamin E