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Effects of bazedoxifene alone and with conjugated equine estrogens on coronary and peripheral artery atherosclerosis in postmenopausal monkeys

Clarkson, Thomas B. DVM1; Ethun, Kelly F. DVM, PhD1; Chen, Haiying MD, PhD2; Golden, Debbie BS1; Floyd, Edison BS1; Appt, Susan E. DVM1

doi: 10.1097/gme.0b013e318271e59b
Original Articles
Editorial

Objective: The objectives of this study were to evaluate the effects of bazedoxifene acetate (BZA), a new selective estrogen receptor modulator, on coronary and peripheral artery atheroscleroses and to determine if it would antagonize the atheroprotective effects of conjugated equine estrogens (CEE) on a monkey model.

Methods: Ninety-eight surgically postmenopausal monkeys (Macaca fascicularis) were fed a moderately atherogenic diet and randomized to receive no treatment or women’s equivalent doses of BZA (20 mg/d), CEE (0.45 mg/d), or BZA + CEE. The experimental period lasted for 20 months (equivalent to approximately 5 y in humans) during which interim measures of cardiovascular risk factors were made. At the end of the experimental period, the extent and severity of coronary and iliac artery atheroscleroses were quantified.

Results: Body weight, adiposity, fasting glucose concentrations, and plasma lipid profiles were not different among treatment conditions. BZA had no adverse effects on the extent or severity of coronary or common iliac artery atherosclerosis when compared with no treatment. CEE, administered soon after inducing menopause, had robust atheroprotective effects on both the extent and the severity of iliac and coronary artery atheroscleroses. The addition of BZA to CEE treatment antagonized the atheroprotective effects of CEE.

Conclusions: In this nonhuman primate trial, treatment with BZA alone, CEE alone, and combined BZA and CEE does not have significant effects on plasma lipid profiles. CEE markedly inhibits the progression and complications of both coronary and iliac artery atheroscleroses. BZA has no adverse effects on atherosclerosis but attenuates the atheroprotective effects of CEE.

From the Departments of 1Pathology/Comparative Medicine and 2Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC.

Received May 31, 2012; revised and accepted August 2, 2012.

Funding/support: This work was supported by grants from Pfizer Inc. (an investigator-originated grant to T.B.C.) and the Office of the Director, National Institutes of Health (8T32OD010957 to K.F.E.).

Financial disclosure/conflicts of interest: T.B.C. received an investigator-originated grant from Pfizer Inc. and an investigator-originated cardiovascular grant from Merck.

Address correspondence to: Thomas B. Clarkson, DVM, Department of Pathology/Comparative Medicine, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1040. E-mail: tclarkso@wakehealth.edu

© 2013 by The North American Menopause Society.