Tamoxifen Study
Condition: Cardiovascular Diseases; Coronary Disease; Heart Diseases; Hypertension; Myocardial Ischemia
MeSH terms: Cardiovascular Diseases; Heart Diseases; Coronary Disease; Myocardial Ischemia; Ischemia
Study type: Interventional
Phase: Phase 3

Summary: 
      To assess the impact of tamoxifen on development of breast cancer, coronary heart disease,
      and bone fractures. The National Cancer Institute initiated the prevention trial under its
      National Surgical Adjuvant Breast and Bowel Project (NSABP). The National Heart, Lung, and
      Blood Institute provided support to obtain blood pressure and lipid measurements, and
      lipoprotein and selected coagulation factor measurements in a subsample.
    

Detailed description: 
      BACKGROUND:

      Tamoxifen is nominally called an 'anti-estrogen' although it has some estrogen-agonist
      activities and tends to increase plasma endogenous estrogen levels. Several studies have
      confirmed that it decreases plasma total cholesterol and LDL-cholesterol and a review of
      mortality in patients taking tamoxifen as adjuvant therapy for breast cancer indicates a
      decreased number of vascular deaths in women on tamoxifen compared to those not on this
      agent.

      DESIGN NARRATIVE:

      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.
    

Intervention name(s): tamoxifen
Intervention type(s): Drug
Intervention MeSH terms: Tamoxifen
Allocation: Randomized
Primary purpose: Prevention