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Effects of conjugated estrogens/bazedoxifene on lipid and coagulation variables

a randomized placebo- and active-controlled trial

Skouby, Sven O. MD, DMSc1,2; Pan, Kaijie MS3; Thompson, John R. PhD3; Komm, Barry S. PhD3; Mirkin, Sebastian MD3

doi: 10.1097/GME.0000000000000362
Original Articles
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Objective This study aims to evaluate the effects of conjugated estrogens (CE)/bazedoxifene (BZA) on lipid and coagulation variables in a randomized, double-blind, placebo- and active-controlled phase 3 study of nonhysterectomized postmenopausal women.

Methods The Selective estrogens, Menopause, And Response to Therapy (SMART)-5 trial evaluated the efficacy and safety of CE/BZA in postmenopausal women (N = 1,843) with menopausal symptoms. Lipid (N = 1,843) and coagulation (N = 590) variables were assessed in women receiving daily CE 0.45 mg/BZA 20 mg, CE 0.625 mg/BZA 20 mg, BZA 20 mg, CE 0.45 mg/medroxyprogesterone acetate (MPA) 1.5 mg, or placebo for 12 months.

Results At 12 months, CE 0.45 mg/BZA 20 mg, CE 0.625 mg/BZA 20 mg, BZA 20 mg, and CE 0.45 mg/MPA 1.5 mg decreased total cholesterol and low-density lipoprotein cholesterol compared with placebo (P < 0.01 for all). Both CE/BZA doses and CE/MPA increased high-density lipoprotein cholesterol compared with placebo (P < 0.05 for all). CE 0.45 mg/BZA 20 mg had a neutral effect on triglycerides; CE 0.625 mg/BZA 20 mg and CE/MPA increased triglycerides compared with placebo (P < 0.05). Both CE/BZA doses were associated with small but significant effects on hemostasis variables, including reductions in antithrombin, plasminogen activator inhibitor-1, and fibrinogen activity, and an increase in plasminogen activity relative to placebo at 12 months. Incidences of cardiovascular and venous thromboembolic events were similar among treatment groups.

Conclusions This study provides reassurance that CE/BZA does not adversely affect lipid metabolism or hemostatic balance. In accordance, the incidences of venous thromboembolic events and cardiovascular events in postmenopausal women are similar to those observed with placebo.

From the 1Department of Obstetrics and Gynecology, Herlev Hospital, Copenhagen University Hospital, Denmark; 2Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; and 3Pfizer Inc, Collegeville, PA.

Received May 7, 2014; revised and accepted September 3, 2014.

Funding/support: This study was sponsored by Wyeth Research, which was acquired by Pfizer in October 2009. Medical writing support was provided by Katie McClendon, PhD (MedErgy) and Diane M. Sloan, PharmD (Peloton Advantage) and was funded by Pfizer.

Financial disclosure/conflicts of interest: S.O.S. has served as a consultant for Wyeth and has lectured at the International Microwave Symposium 2014. K.P., J.R.T., and B.S.K. are full-time employees of Pfizer. S.M. was a full-time employee of Pfizer at the time the study was conducted.

Address correspondence to: Sven O. Skouby, MD, DMSc, Department of Obstetrics and Gynecology, Herlev Hospital, 63 C7F, Herlev Ringvej DK 2730, Herlev, Denmark. E-mail: Sven.Olaf.Skouby@regionh.dk

© 2015 by The North American Menopause Society.