Cardiovascular safety of conjugated estrogens plus bazedoxifene: Meta-analysis of the SMART trials

Climacteric

Volumn 18, Issue 4, 2015, Pages 503-511

  Komm, B S ^a   Thompson, J R ^a   Mirkin, S ^a  

^a PFIZER INC   (United States)

Author keywords

adverse effects; bazedoxifene; Conjugated estrogens; coronary artery disease; safety; stroke; transient ischemic attack; venous thromboembolism

Indexed keywords

BAZEDOXIFENE PLUS CONJUGATED ESTROGEN; PLACEBO; BAZEDOXIFENE; CONJUGATED ESTROGEN; INDOLE DERIVATIVE; SELECTIVE ESTROGEN RECEPTOR MODULATOR;

ARTICLE; ATTRIBUTABLE RISK; BODY WEIGHT; BRAIN ISCHEMIA; CEREBROVASCULAR ACCIDENT; CEREBROVASCULAR DISEASE; DIASTOLIC BLOOD PRESSURE; DRUG EFFICACY; DRUG SAFETY; FEMALE; HEART INFARCTION; HUMAN; ISCHEMIC HEART DISEASE; MENOPAUSAL SYNDROME; META ANALYSIS; PHASE 3 CLINICAL TRIAL (TOPIC); POSTMENOPAUSE; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); RISK FACTOR; SUPERFICIAL THROMBOPHLEBITIS; SYSTOLIC BLOOD PRESSURE; TRANSIENT ISCHEMIC ATTACK; TREATMENT DURATION; VENOUS THROMBOEMBOLISM; ADVERSE EFFECTS; CHEMICALLY INDUCED; CORONARY DISEASE; DRUG COMBINATION; ESTROGEN THERAPY; INCIDENCE; PROCEDURES; RISK ASSESSMENT; STROKE;

CORONARY DISEASE; DRUG THERAPY, COMBINATION; ESTROGEN REPLACEMENT THERAPY; ESTROGENS, CONJUGATED (USP); FEMALE; HUMANS; INCIDENCE; INDOLES; POSTMENOPAUSE; RANDOMIZED CONTROLLED TRIALS AS TOPIC; RISK ASSESSMENT; RISK FACTORS; SELECTIVE ESTROGEN RECEPTOR MODULATORS; STROKE; VENOUS THROMBOEMBOLISM;

EID: 84924225664     PISSN: 13697137     EISSN: 14730804     Source Type: Journal    
DOI: 10.3109/13697137.2014.992011     Document Type: Article

References (42)

1. Politi M C, Schleinitz M D, Col N F. R evisiting the duration of vasomotor symptoms of menopause: A meta-analysis. J Gen Intern Med 2008; 23: 1507-13
2. Riggs B L, Khosla S, Melton L J, III. A unitary model for involutional osteoporosis: estrogen deficiency causes both type I and type II osteoporosis in postmenopausal women and contributes to bone loss in aging men. J Bone Miner Res 1998; 13: 763-73
3. North American Menopause Society. Management of osteoporosis in postmenopausal women: 2010 position statement of The North American Menopause Society. Menopause 2010; 17: 25-54
4. Grady D, Gebretsadik T, Kerlikowske K, Ernster V, Petitti D. Hormone replacement therapy and endometrial cancer risk: A meta-analysis. Obstet Gynecol 1995; 85: 304-13
5. North American Menopause Society. T he 2012 hormone therapy position statement of The North American Menopause Society. Menopause 2012; 19: 257-71
6. American College of Obsetrics and Gynecology. P ractice bulletin no. 141: Management of menopausal symptoms. Obstet Gynecol 2014; 123:202-16
7. Manson JE, Chlebowski RT, Stefanick ML, et al. Menopausal hormone therapy and health outcomes during the intervention and extended poststopping phases of the Women's Health Initiative randomized trials. JAMA 2013; 310: 1353-68
8. Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial. JAMA 2002; 288: 321-33
9. Barnabei VM, Cochrane BB, Aragaki AK, et al. Menopausal symptoms and treatment-related effects of estrogen and progestin in the Women's Health Initiative. Obstet Gynecol 2005; 105: 1063-73
10. Lethaby A, Suckling J, Barlow D, et al. H ormone replacement therapy in postmenopausal women: endometrial hyperplasia and irregular bleeding. Cochrane Database Syst Rev 2004;C D000402
11. Wassertheil-Smoller S, Hendrix S L, Limacher M, et al. E ffect of estrogen plus progestin on stroke in postmenopausal women: The Women's Health Initiative: A randomized trial. JAMA 2003; 289: 2673-84
12. Anderson GL, Limacher M, Assaf AR, et al. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: The Women's Health Initiative randomized controlled trial. JAMA 2004; 291: 1701-12
13. Duavee [package insert]. Philadelphia, PA: Wyeth Pharmaceuticals Inc, Asubsidiary of Pfizer Inc.; 2013
14. Archer DF, Lewis V, Carr BR, Olivier S, Pickar JH. Bazedoxifene/ conjugated estrogens (BZA/CE): incidence of uterine bleeding in postmenopausal women. Fertil Steril 2009; 92: 1039-44
15. Bachmann G, Bobula J, Mirkin S. E ffects of bazedoxifene/ conjugated estrogens on quality of life in postmenopausal women with symptoms of vulvar/vaginal atrophy. Climacteric 2010; 13: 132-40
16. Harvey J A, Pinkerton J V, Baracat E C, et al. B reast density changes in a randomized controlled trial evaluating bazedoxifene/conjugated estrogens. Menopause 2013; 20: 138-45
17. Kagan R, Williams RS, Pan K, Mirkin S, Pickar JH. A randomized, placebo-and active-controlled trial of bazedoxifene/ conjugated estrogens for treatment of moderate to severe vulvar/ vaginal atrophy in postmenopausal women. Menopause 2010; 17: 281-9
18. Lindsay R, Gallagher JC, Kagan R, Pickar JH, Constantine G. Efficacy of tissue-selective estrogen complex of bazedoxifene/ conjugated estrogens for osteoporosis prevention in at-risk postmenopausal women. Fertil Steril 2009; 92: 1045-52
19. Lobo R A, Pinkerton J V, Gass M L, et al. E valuation of bazedoxifene/ conjugated estrogens for the treatment of menopausal symptoms and effects on metabolic parameters and overall safety profile. Fertil Steril 2009; 92: 1025-38
20. Mirkin S, Komm B S, Pan K, Chines A A. E ffects of bazedoxifene/ conjugated estrogens on endometrial safety and bone in postmenopausal women. Climacteric 2013; 16: 338-46
21. Pickar J H, Yeh I T, Bachmann G, SperoffL. E ndometrial effects of a tissue selective estrogen complex containing bazedoxifene/ conjugated estrogens as a menopausal therapy. Fertil Steril 2009; 92: 1018-24
22. Pinkerton JV, Utian WH, Constantine GD, Olivier S, Pickar JH. Relief of vasomotor symptoms with the tissue-selective estrogen complex containing bazedoxifene/conjugated estrogens: A randomized, controlled trial. Menopause 2009; 16: 1116-24
23. Pinkerton JV, Pan K, Abraham L, et al. Sleep parameters and health-related quality of life with bazedoxifene/conjugated estrogens: A randomized trial. Menopause 2014; 21: 252-9
24. Pinkerton JV, Harvey JA, Pan K, et al. Breast effects of bazedoxifene-conjugated estrogens: A randomized controlled trial. Obstet Gynecol 2013; 121: 959-68
25. Utian W, Yu H, Bobula J, et al. Bazedoxifene/conjugated estrogens and quality of life in postmenopausal women. Maturitas 2009; 63: 329-35
26. Pinkerton J V, Harvey J A, Lindsay R, et a l. E ffects of bazedoxifene/ conjugated estrogens on the endometrium and bone: A randomized trial. J Clin Endocrinol Metab 2014; 99: E189-98
27. Archer DF, Pinkerton J, Kagan R, et al. Gynecologic safety of bazedoxifene/conjugated estrogens: pooled analysis of phase 3 trials [abstract]. Presented at The North American Menopause Society; October 3-6, 2012; Kissimmee, FL
28. Barrett-Connor E, Mosca L, Collins P, et al. Effects of raloxifene on cardiovascular events and breast cancer in postmenopausal women. N Engl J Med 2006; 355: 125-37
29. Christiansen C, Chesnut C H, III, Adachi J D, et al. S afety of bazedoxifene in a randomized, double-blind, placebo-and activecontrolled Phase 3 study of postmenopausal women with osteoporosis. BMC Musculoskelet Disord 2010; 11: 130
30. Rossouw J E, Prentice R L, Manson J E, et al. P ostmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause. JAMA 2007; 297: 1465-77
31. Hackshaw A, Roughton M, Forsyth S, et al. L ong-term benefits of 5 years of tamoxifen: 10-year follow-up of a large randomized trial in women at least 50 years of age with early breast cancer. J Clin Oncol 2011; 29: 1657-63
32. Schierbeck LL, Rejnmark L, Tofteng CL, et al. Effect of hormone replacement therapy on cardiovascular events in recently postmenopausal women: randomised trial. BMJ 2012; 345: e6409
33. Mirkin S, Ryan KA, Pan K, Chines AA, Lobo RA. A pooled analysis of the effects of bazedoxifene/conjugated estrogens on lipid parameters from the selective estrogens, menopause, and response to therapy trials [abstract]. Endocr Rev 2012; 33: SAT-30
34. Skouby S O, Lobo R A, Ryan K A, Thompson J R, Komm B S, Chines AA. Low risk of thrombophilia with bazedoxifene/conjugated estrogens: summary of pooled coagulation data from the selective estrogens, menopause, and response to therapy trials [abstract]. Presented at the Annual Meeting of the Endocrine Society; June 23-26, 2012; Houston, TX
35. Cushman M, Kuller LH, Prentice R, et al. Estrogen plus progestin and risk of venous thrombosis. JAMA 2004; 292: 1573-80
36. Curb JD, Prentice RL, Bray PF, et al. Venous thrombosis and conjugated equine estrogen in women without a uterus. Arch Intern Med 2006; 166: 772-80
37. de Villiers TJ, Chines AA, Palacios S, et a l. Safety and tolerability of bazedoxifene in postmenopausal women with osteoporosis: results of a 5-year, randomized, placebo-controlled phase 3 trial. Osteoporos Int 2011; 22: 567-76
38. Wardell SE, Nelson ER, Chao CA, McDonnell DP. Bazedoxifene exhibits antiestrogenic activity in animal models of tamoxifenresistant breast cancer: implications for treatment of advanced disease. Clin Cancer Res 2013; 19: 2420-31
39. Lewis-Wambi J S, Kim H, Curpan R, et al. T he selective estrogen receptor modulator bazedoxifene inhibits hormone-independent breast cancer cell growth and down-regulates estrogen receptor alpha and cyclin D1. Mol Pharmacol 2011; 80: 610-20
40. Ethun KF, Wood CE, Cline JM, et al. Endometrial profile of bazedoxifene acetate alone and in combination with conjugated equine estrogens in a primate model. Menopause 2013; 20: 777-84
41. Ethun K F, Wood C E, Register T C, et al. E ffects of bazedoxifene acetate with and without conjugated equine estrogens on the breast of postmenopausal monkeys. Menopause 2012; 19: 1242-52
42. Kulak J, Jr., Fischer C, Komm B, Taylor HS. Treatment with bazedoxifene, a selective estrogen receptor modulator, causes regression of endometriosis in a mouse model. Endocrinology 2011; 152: 3226-32