Impact of cyclooxygenase inhibitors in the Women's Health Initiative hormone trials: secondary analysis of a randomized trial
Authors
Hsia, JudithManson, JoAnn E.
Kuller, Lewis H.
Pettinger, Mary B.
Choe, John H.
Langer, Robert D.
Limacher, Marian C.
Oberman, Albert
Ockene, Judith K.
O'Sullivan, Mary Jo
Robinson, Jennifer G.
UMass Chan Affiliations
Department of Medicine, Division of Preventive and Behavioral MedicineDocument Type
Journal ArticlePublication Date
2006-09-29Keywords
Cyclooxygenase InhibitorsEstrogens
Estrogens, Conjugated (USP)
Female
Follow-Up Studies
*Hormone Replacement Therapy
Humans
Postmenopause
Myocardial Infarction
Myocardial Revascularization
United States
Enzymes and Coenzymes
Hormones, Hormone Substitutes, and Hormone Antagonists
Life Sciences
Medicine and Health Sciences
Therapeutics
Women's Studies
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OBJECTIVES: We evaluated the hypothesis that cyclooxygenase (COX) inhibitor use might have counteracted a beneficial effect of postmenopausal hormone therapy, and account for the absence of cardioprotection in the Women's Health Initiative hormone trials. Estrogen increases COX expression, and inhibitors of COX such as nonsteroidal anti-inflammatory agents appear to increase coronary risk, raising the possibility of a clinically important interaction in the trials. DESIGN: The hormone trials were randomized, double-blind, and placebo-controlled. Use of nonsteroidal anti-inflammatory drugs was assessed at baseline and at years 1, 3, and 6. SETTING: The Women's Health Initiative hormone trials were conducted at 40 clinical sites in the United States. PARTICIPANTS: The trials enrolled 27,347 postmenopausal women, aged 50-79 y. INTERVENTIONS: We randomized 16,608 women with intact uterus to conjugated estrogens 0.625 mg with medroxyprogesterone acetate 2.5 mg daily or to placebo, and 10,739 women with prior hysterectomy to conjugated estrogens 0.625 mg daily or placebo. OUTCOME MEASURES: Myocardial infarction, coronary death, and coronary revascularization were ascertained during 5.6 y of follow-up in the estrogen plus progestin trial and 6.8 y of follow-up in the estrogen alone trial. RESULTS: Hazard ratios with 95% confidence intervals were calculated from Cox proportional hazard models stratified by COX inhibitor use. The hazard ratio for myocardial infarction/coronary death with estrogen plus progestin was 1.13 (95% confidence interval 0.68-1.89) among non-users of COX inhibitors, and 1.35 (95% confidence interval 0.86-2.10) among continuous users. The hazard ratio with estrogen alone was 0.92 (95% confidence interval 0.57-1.48) among non-users of COX inhibitors, and 1.08 (95% confidence interval 0.69-1.70) among continuous users. In a second analytic approach, hazard ratios were calculated from Cox models that included hormone trial assignment as well as a time-dependent covariate for medication use, and an interaction term. No significant interaction was identified. CONCLUSIONS: Use of COX inhibitors did not significantly affect the Women's Health Initiative hormone trial results.Source
PLoS Clin Trials. 2006 Sep 29;1(5):e26. Link to article on publisher's site
DOI
10.1371/journal.pctr.0010026Permanent Link to this Item
http://hdl.handle.net/20.500.14038/50915PubMed ID
17016543Related Resources
Rights
Copyright: © 2006 Hsia et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.ae974a485f413a2113503eed53cd6c53
10.1371/journal.pctr.0010026
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