Women's Angiographic Vitamin and Estrogen Trial (WAVE)
Condition: Cardiovascular Diseases; Coronary Arteriosclerosis; Coronary Disease; Heart Diseases; Myocardial Ischemia; Postmenopause
MeSH terms: Cardiovascular Diseases; Heart Diseases; Coronary Disease; Coronary Artery Disease; Myocardial Ischemia; Arteriosclerosis; Ischemia
Study type: Interventional
Phase: Phase 3

Summary: 
      To assess whether hormonal replacement therapy and/or antioxidant treatment would stabilize
      or inhibit progression, and induce regression of coronary plaques. The mechanisms by which
      these treatments modified atherosclerosis in women were also explored.
    

Detailed description: 
      BACKGROUND:

      Coronary artery disease is the leading cause of death in the United States, accounting for
      over 500,000 deaths each year. Although the onset of coronary artery disease is delayed in
      women, it is the single most important cause of death in women over the entire life span.
      Indeed, because more women than men survive to old age, mortality due to coronary artery
      disease for all ages combined is as great in women as in men. Furthermore, once they present
      with clinical evidence of coronary artery disease, women have a prognosis as poor as, or even
      worse, than that for men. In part, this may be due to late recognition of coronary artery
      disease in women, less intensive treatment of women, or a more adverse risk profile in women
      who develop coronary artery disease. The report of a recent Working Group on Angiographic
      Trials of Atherosclerosis Prevention notes that, compared to males, females who develop
      coronary artery disease, have various different characteristics which may affect the vascular
      response to lipid-altering interventions. These differences led the report to question
      whether the mechanisms and clinical benefits of lipid-altering agents may be different in men
      and women. It further noted that angiographic trials conducted to date have been based
      primarily upon the cholesterol-lowering treatments of diet or drugs and suggested that other
      approaches based upon the lipid hypothesis could profitably be tested and should be given the
      highest priority at this time; specifically recommended were trials of hormone replacement
      and antioxidant therapy in women.

      DESIGN NARRATIVE:

      Subjects were randomized into a 2 x 2 factorial trial of hormone replacement therapy and
      antioxidant therapy. Women were randomized into four treatment groups: both active hormone
      replacement and antioxidant; active hormone replacement therapy and antioxidant placebo;
      active antioxidant therapy and hormone replacement placebo; double placebo plus usual care.
      Hormone replacement therapy consisted of estrogen plus a progestin (PremPro) for all
      gynecologically intact women, and unopposed estrogen (Premarin) for women with
      hysterectomies. Antioxidants consisted of a combination of vitamin E and vitamin C.
      Angiographic change was a primary endpoint of this trial. The study was double-blind to the
      extent permitted by the interventions; however, it was fully-blinded with respect to outcome
      variables. Recruitment ended in August 1999. The mean duration of follow-up was approximately
      three years.

      The NHLBI awarded R01HL68397 in April 2001 as an ancillary study to WAVE. The study entitled
      "Modifying Oxidative Damage in WAVE" has its on site on this database.

      The study completion date listed in this record was obtained from the "End Date" entered in
      the Protocol Registration and Results System (PRS) record.
    

Intervention name(s): estrogen replacement therapy; estrogens, conjugated; progesterone; hormone replacement therapy; supplementation, food; ascorbic acid; vitamin e
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug; Drug
Intervention MeSH terms: Ascorbic Acid; Vitamin E; Hormones; Progesterone; Estrogens, Conjugated (USP); Estrogens
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: Double
Primary purpose: Prevention