Subjects were randomized to receive 10 mg of tamoxifen two times a day or to placebo. The primary endpoint was prevention of invasive breast cancer. The secondary endpoint was the effects on fatal and nonfatal cardiovascular events (coronary heart disease, stroke, and thromboembolic disease) and fractures. A total of 13,388 women at increased risk for breast cancer were randomly assigned to receive either tamoxifen (20 milligrams per day) or placebo. Cardiovascular follow-up was available for 13,194 women. The median follow-up was 57 months; the mean follow-up was 49 months. During long-term follow-up, 76 percent of the tamoxifen participants were compliant with the study therapy; 83 percent were compliant through 24 months of follow-up. To evaluate the effects of tamoxifen in women with and without pre-existing heart disease, the 13,388 women enrolled at the 131 clinical sites were divided into subgroups of those with and without a self-reported history of clinical coronary heart disease, defined as myocardial infarction or angina prior to randomization. Medical records for subjects with suspected cardiovascular events were collected by the clinical sites and forwarded to the NSABP Operations Center for adjudication by investigators who were blinded to treatment assignment. Primary cardiovascular events included fatal myocardial infarction, Q-wave myocardial infarction, and non-Q-wave myocardial infarction. Secondary cardiovascular events included unstable angina (angina requiring hospitalization) and severe angina (angina requiring revascularization). All subjects were included in the analysis using the intent-to-treat principle.