Women's Angiographic Vitamin and Estrogen Trial (WAVE)
Women's Angiographic Vitamin and Estrogen Trial (WAVE)
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.
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.
Postmenopausal women, up to age 86, with angiographically documented coronary artery
 disease of at least 15 percent, but no more than 75 percent occlusion.