Postmenopausal hormone therapy increases risk for venous thromboembolic disease - The heart and estrogen/progestin replacement study

Background: Oral contraceptive use increases risk for venous thromboembolis m, but data on the effect of postmenopausal hormone therapy are limited. Objective: To determine the effect of therapy with estrogen plus progestin on risk for venous thromboembolic events in postmenopausal women. Design: Randomized, double-blind, placebo-controlled trial. Setting: 20 clinical centers in the United States. Participants: 2763 postmenopausal women younger than 80 years of age (mean age, 67 years) who had coronary heart disease but no previous Venous thromb oembolism and had not had a hysterectomy. Intervention: Conjugated equine estrogens, 0.625 mg, plus medroxyprogestero ne acetate, 2.5 mg, in one tablet (n = 1380) or placebo that was identical in appearance (n = 1383). Measurements: Documented deep venous thrombosis or pulmonary embolism. Results: During an average of 4.1 years of follow-up, 34 women in the hormo ne therapy group and 13 in the placebo group experienced Venous thromboembo lic events (relative hazard, 2.7 [95% CI, 1.4 to 5.0] [P = 0.003]; excess r isk, 3.9 per 1000 woman-years [CI, 1.4 to 6.4 per 1000 woman-years]; number needed to treat for harm, 256 [CI, 157 to 692]). In multivariate analysis, the risk for venous thromboembolism was increased among women who had lowe r-extremity fractures (relative hazard, 18.1 [CI, 5.4 to 60.4]) or cancer ( relative hazard, 3.9 [Cl, 1.6 to 9.4]) and for 90 days after inpatient surg ery (relative hazard, 4.9 [CI, 2.4 to 9.8]) or nonsurgical hospitalization (relative hazard, 5.7 [Ct, 3.0 to 10.8]). Risk was decreased with aspirin ( relative hazard, 0.5 [CI, 0.2 to 0.8]) or statin use (relative hazard, 0.5 [CI, 0.2 to 0.9]). Conclusions: Postmenopausal therapy with estrogen plus progestin increases risk for venous thromboembolism in women with coronary heart disease. This risk should be considered when the risks and benefits of therapy are being weighed.