Deborah Grady, MD, MPH; Nanette K. Wenger, MD; David Herrington, MD, MHS; Steven Khan, MD; Curt Furberg, MD; Donald Hunninghake, MD; Eric Vittinghoff, PhD; Stephen Hulley, MD, MPH; for the Heart and Estrogen/progestin Replacement Study Research Group
Acknowledgments: The authors thank Josephine Fong for performing statistical analyses.
Grant Support: By Wyeth-Ayerst Laboratories.
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Current Author Addresses: Drs. Grady, Vittinghoff, and Hulley: University of California, San Francisco, 74 New Montgomery Street, Suite 600, San Francisco, CA 94105.
Dr. Wenger: Emory University School of Medicine, 69 Butler Street SE, Atlanta, GA 30303.
Drs. Herrington and Furberg: Wake Forest University School of Medicine, One Medical Center Boulevard, Winston-Salem, NC 27157-1066.
Dr. Khan: Cedars-Sinai Medical Center, 444 South San Vicente Boulevard, Suite 903, Los Angeles, CA 90048-4174.
Dr. Hunninghake: Heart Disease Prevention Clinic, Box 192, 151 Variety Club Heart and Research Center, 401 East River Parkway, Minneapolis, MN 55455.
Author Contributions: Conception and design: D. Grady, N.K. Wenger, S. Hulley.
Analysis and interpretation of the data: D. Grady, N.K. Wenger, D. Herrington, S. Khan, C. Furberg, D. Hunninghake, E. Vittinghoff, S. Hulley.
Drafting of the article: D. Grady.
Critical revision of the article for important intellectual content: D. Grady, N.K. Wenger, D. Herrington, S. Khan, C. Furberg, D. Hunninghake, S. Hulley.
Final approval of the article: D. Grady, N.K. Wenger, D. Herrington, S. Khan, C. Furberg, D. Hunninghake, E. Vittinghoff, S. Hulley.
Provision of study materials or patients: N.K. Wenger, D. Herrington, S. Khan, D. Hunninghake.
Statistical expertise: E. Vittinghoff, S. Hulley.
Obtaining of funding: D. Grady, C. Furberg, D. Hunninghake, S. Hulley.
Administrative, technical, or logistic support: D. Grady, S. Hulley.
Collection and assembly of data: D. Grady, S. Khan.
Oral contraceptive use increases risk for venous thromboembolism, but data on the effect of postmenopausal hormone therapy are limited.
To determine the effect of therapy with estrogen plus progestin on risk for venous thromboembolic events in postmenopausal women.
Randomized, double-blind, placebo-controlled trial.
20 clinical centers in the United States.
2763 postmenopausal women younger than 80 years of age (mean age, 67 years) who had coronary heart disease but no previous venous thromboembolism and had not had a hysterectomy.
Conjugated equine estrogens, 0.625 mg, plus medroxyprogesterone acetate, 2.5 mg, in one tablet (n = 1380) or placebo that was identical in appearance (n = 1383).
Documented deep venous thrombosis or pulmonary embolism.
During an average of 4.1 years of follow-up, 34 women in the hormone therapy group and 13 in the placebo group experienced venous thromboembolic events (relative hazard, 2.7 [95% CI, 1.4 to 5.0] [P = 0.003]; excess risk, 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 lower-extremity fractures (relative hazard, 18.1 [CI, 5.4 to 60.4]) or cancer (relative hazard, 3.9 [CI, 1.6 to 9.4]) and for 90 days after inpatient surgery (relative hazard, 4.9 [CI, 2.4 to 9.8]) or nonsurgical hospitalization (relative hazard, 5.7 [CI, 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]).
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.
Grady D, Wenger NK, Herrington D, Khan S, Furberg C, Hunninghake D, et al. Postmenopausal Hormone Therapy Increases Risk for Venous Thromboembolic Disease: The Heart and Estrogen/progestin Replacement Study. Ann Intern Med. 2000;132:689–696. doi: 10.7326/0003-4819-132-9-200005020-00002
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Published: Ann Intern Med. 2000;132(9):689-696.
Endocrine and Metabolism, Venous Thromboembolism.
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