Trial Information

Women's Health Study of Low-dose Aspirin and Vitamin E 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.