title: Clinical outcomes in patients with atrial fibrillation according to sex during anticoagulation with apixaban or warfarin: a secondary analysis of a randomized controlled trial.
abstract: OBJECTIVE
  To assess clinical outcomes, efficacy, and safety according to sex during anticoagulation with apixaban compared with warfarin in patients with atrial fibrillation.
  
  
  RESULTS
  Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) was a randomized, double-blind, placebo-controlled, multicentre trial that included 11 785 (64.7%) men and 6416 (35.3%) women with atrial fibrillation or flutter randomized to receive either warfarin or apixaban. The primary efficacy endpoint was stroke or systemic embolism; secondary efficacy endpoints were death from any cause and cardiovascular death. The primary safety endpoint was major bleeding; secondary safety endpoints were a composite of major bleeding and non-major clinically relevant bleeding. The risk of stroke or systemic embolism was similar in women vs. men [adjusted hazard ratio (adjHR): 0.91; 95% confidence interval (CI): 0.74-1.12; P = 0.38]. However, among patients with history of stroke or transient ischaemic attack, women had a lower risk of recurrent stroke compared with men (adjHR: 0.70; 95% CI: 0.50-0.97; P = 0.036). Women also had a lower risk of all-cause death (adjHR: 0.63; 95% CI: 0.55-0.73; P < 0.0001) and cardiovascular death (adjHR: 0.62; 95% CI: 0.51-0.75; P < 0.0001), and a trend towards less major bleeding (adjHR: 0.86; 95% CI: 0.74-1.01; P = 0.066) and major or non-major clinically relevant bleeding (adjHR: 0.89; 95% CI: 0.80-1.00; P = 0.049). The efficacy and safety benefits of apixaban compared with warfarin were consistent regardless of sex.
  
  
  CONCLUSIONS
  In the ARISTOTLE trial, women had a similar rate of stroke or systemic embolism but a lower risk of mortality and less clinically relevant bleeding than men. The efficacy and safety benefits of apixaban compared with warfarin were consistent in men and women.
  
  
  BACKGROUND
  ARISTOTLE ClinicalTrials.gov number, NCT00412984.
authors.affiliation: University of Medicine and Pharmacy Carol Davila, Bucharest, Romania Department of Cardiology, University and Emergency Hospital of Bucharest, 169 Splaiul Independentei, Sector 5, Bucharest, Romania vinereanu@gmail.com.
authors.forename: Dragos
authors.initials: D
authors.lastname: Vinereanu
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA.
authors.forename: Susanna R
authors.initials: SR
authors.lastname: Stevens
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA.
authors.forename: John H
authors.initials: JH
authors.lastname: Alexander
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA.
authors.forename: Sana M
authors.initials: SM
authors.lastname: Al-Khatib
authors.affiliation: Dante Pazzanese Institute of Cardiology, Sao Paulo, Brazil.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Avezum
authors.affiliation: INECO Neurociencias Oroño, Rosario, Argentina.
authors.forename: Marıa Cecilia
authors.initials: MC
authors.lastname: Bahit
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA.
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Granger
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA.
authors.forename: Renato D
authors.initials: RD
authors.lastname: Lopes
authors.affiliation: Oslo University Hospital and University of Oslo, Oslo, Norway.
authors.forename: Sigrun
authors.initials: S
authors.lastname: Halvorsen
authors.affiliation: Bristol-Myers Squibb, Princeton, NJ, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Hanna
authors.affiliation: Hospital Unit West and Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Steen
authors.initials: S
authors.lastname: Husted
authors.affiliation: Boston University Medical Center, Boston, MA, USA.
authors.forename: Elaine M
authors.initials: EM
authors.lastname: Hylek
authors.affiliation: University of Medicine and Pharmacy Carol Davila, Bucharest, Romania Department of Cardiology, University and Emergency Hospital of Bucharest, 169 Splaiul Independentei, Sector 5, Bucharest, Romania.
authors.forename: Andrei D
authors.initials: AD
authors.lastname: Mărgulescu
authors.affiliation: Uppsala Clinical Research Center and Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Wallentin
authors.affiliation: Department of Cardiology B, Oslo University Hospital, and Institute of Clinical Sciences, University of Oslo, Oslo, Norway.
authors.forename: Dan
authors.initials: D
authors.lastname: Atar
mesh_terms: D000328:Adult; D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000401:mortality; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011720:Pyrazoles / Q000627:therapeutic use*; D011728:Pyridones / Q000627:therapeutic use*; D012307:Risk Factors; D017678:Sex Distribution; D020521:Stroke / Q000517:prevention & control; D016896:Treatment Outcome; D014859:Warfarin / Q000627:therapeutic use*
chemical_list: D000925:Anticoagulants; D011720:Pyrazoles; D011728:Pyridones; C522181:apixaban; D014859:Warfarin
keywords: Anticoagulation; Apixaban; Atrial fibrillation; Sex; Stroke prevention; Warfarin