Conjugated Equine Estrogens and Coronary Heart Disease: The Women???s Health Initiative

In the Women's Health Initiative study, 10,739 postmenopausal women 50 to 79 years of age who had undergone hysterectomy were randomized to receive 0.625 mg daily of conjugated equine estrogens (CEE; Premarin) or placebo. The participants were seen at 40 clinical centers in the United States starting in 1993 and continuing until the trial was ended after 6.8 years rather than after 8.5 years as planned. Follow up averaged 7.1 years. At the end of the study, 54% of women assigned to receive CEE and 53.5% of those assigned to placebo had stopped using their study medication. The hazard ratio (HR) for coronary heart disease (CHD) events (coronary death and nonfatal myocardial infarction) was 0.95 (nominal 95% confidence interval [CI], 0.79-1.16). The HR for women who took at least 80% of assigned medication was 0.91 (nominal 95% CI, 0.69-1.20). The HR for the primary outcome at year 6 or later was 0.81 (95% CI, 0.60-1.10). Hazard ratios increased progressively with advancing age. The HR for women 50 to 54 years of age at baseline was 0.60 (95% CI, 0.25-1.44). Younger women had coronary revascularization less frequently when given CEE rather than placebo. For women aged 50 to 59 years at baseline, the HR of a composite outcome (myocardial infarction, coronary death, coronary revascularization, and confirmed angina) was 0.66 (95% CI, 0.45-0.96). In women aged 60 or over, secondary coronary outcomes did not differ between the CEE and placebo groups. CEE provided no overall protection against coronary death or nonfatal myocardial infarction in these posthysterectomy women, although a somewhat lower risk of CHD events was a possibility in women 50 to 59 years of age at baseline who received CEE.