title: Cardiovascular safety of conjugated estrogens plus bazedoxifene: meta-analysis of the SMART trials.
abstract: OBJECTIVE
  Five randomized, phase-3 trials demonstrated the efficacy and safety of conjugated estrogens/bazedoxifene (CE/BZA) in treating menopausal symptoms and preserving bone. This pooled analysis of these studies describes the cardiovascular safety of CE/BZA.
  
  
  METHODS
  We pooled cardiovascular adjudicated safety data from healthy, non-hysterectomized, postmenopausal women who received ≥ 1 dose of CE 0.45 mg/BZA 20 mg (n = 1585), CE 0.625 mg/BZA 20 mg (n = 1583), any CE/BZA dose (n = 4868), or placebo (n = 1241) for up to 2 years in five trials. Venous thromboembolic events (VTEs), coronary heart disease (CHD), and cerebrovascular events were reviewed by three different independent adjudication committees and summarized using a meta-analytic approach.
  
  
  RESULTS
  The rate of VTEs per 1000 woman-years (95% confidence interval, CI) was 0.3 (0.0-2.0) in women taking CE 0.45 mg/BZA 20 mg, 0 (0.0-1.5) in those taking CE 0.625 mg/BZA 20 mg, 0.7 (0.0-1.5) among women taking any CE/BZA dose, and 0.6 (0.0-2.9) with placebo. The incidence of stroke per 1000 woman-years (95% CI) was 0.4 (0.0-2.4), 0.2 (0.0-1.9), 0.44 (0.0-1.1), and 0.0 (0.0-1.7), respectively. The CHD rate per 1000 woman-years was 2.6 (0.0-5.6), 1.4 (0.0-3.9), 2.4 (1.00-3.7) and 2.0 (0.0-5.2). Compared with placebo, relative risk (95% CI) with any CE/BZA dose was 0.5 (0.1-1.8) for VTE, 0.5 (0.1-2.6) for stroke, and 0.63 (0.23-1.74) for CHD.
  
  
  CONCLUSIONS
  Up to 2 years of CE 0.45 or CE 0.625 mg with BZA 20 mg had an acceptable cardiovascular safety profile, with rates of stroke and CHD comparable to placebo in healthy postmenopausal women. VTE risk was low.
authors.affiliation: Pfizer Inc , Collegeville, PA.
authors.forename: B S
authors.initials: BS
authors.lastname: Komm
authors.forename: J R
authors.initials: JR
authors.lastname: Thompson
authors.forename: S
authors.initials: S
authors.lastname: Mirkin
mesh_terms: D003327:Coronary Disease / Q000139:chemically induced* / Q000453:epidemiology; D004359:Drug Therapy, Combination; D015914:Estrogen Replacement Therapy / Q000009:adverse effects* / Q000379:methods; D004966:Estrogens, Conjugated (USP) / Q000009:adverse effects*; D005260:Female; D006801:Humans; D015994:Incidence; D007211:Indoles / Q000009:adverse effects*; D017698:Postmenopause; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D012307:Risk Factors; D020845:Selective Estrogen Receptor Modulators / Q000009:adverse effects*; D020521:Stroke / Q000139:chemically induced* / Q000453:epidemiology; D054556:Venous Thromboembolism / Q000139:chemically induced* / Q000453:epidemiology
chemical_list: D004966:Estrogens, Conjugated (USP); D007211:Indoles; D020845:Selective Estrogen Receptor Modulators; C447119:bazedoxifene
keywords: ADVERSE EFFECTS; BAZEDOXIFENE; CONJUGATED ESTROGENS; CORONARY ARTERY DISEASE; SAFETY; STROKE; TRANSIENT ISCHEMIC ATTACK; VENOUS THROMBOEMBOLISM