Peripheral arterial disease in randomized trial of estrogen with progestinin women with coronary heart disease - The heart and estrogen/progestin replacement study

Background-Postmenopausal estrogen use has been associated with reduced car otid atherosclerosis in observational studies, but this relationship has no t been confirmed in a clinical trial. The impact of estrogen on atheroscler otic disease in other peripheral arteries is unknown. Methods and Results-Postmenopausal women with coronary heart disease (CHD) and an intact uterus (n=2763)were randomly assigned to conjugated equine es trogens (0.625 mg) combined with medroxyprogesterone acetate (2.5 mg) daily or to placebo in a secondary CHD prevention trial. This analysis focuses o n incident peripheral arterial procedures and deaths in the 2 treatment gro ups; peripheral vascular disease was a predefined secondary outcome. During a mean of 4.1 years of follow-up, 311 peripheral arterial events were repo rted in 213 women, an annual incidence of 2.9%. The number of women who had peripheral arterial events was 99 among those assigned to active estrogen/ progestin and 114 among those assigned to placebo, a nonsignificant differe nce (relative hazard 0.87, 95% CI 0.66 to 1.14), In the placebo group, hype rtension and diabetes mellitus were independently associated with higher ra tes of peripheral arterial events, and plasma HDL cholesterol and body mass index were associated with lower rates of peripheral arterial events. In t he estrogen/progestin group, current smoking and diabetes ware independent predictors of peripheral arterial events. Incident peripheral arterial dise ase was not a significant predictor of coronary, cardiovascular, or total m ortality. Conclusions-Treatment with oral conjugated estrogen plus medroxyprogesteron e acetate was not associated with a significant reduction in incident perip heral arterial events in postmenopausal women with preexisting CHD.