title: Apixaban versus warfarin in patients with atrial fibrillation.
abstract: BACKGROUND
  Vitamin K antagonists are highly effective in preventing stroke in patients with atrial fibrillation but have several limitations. Apixaban is a novel oral direct factor Xa inhibitor that has been shown to reduce the risk of stroke in a similar population in comparison with aspirin.
  
  
  METHODS
  In this randomized, double-blind trial, we compared apixaban (at a dose of 5 mg twice daily) with warfarin (target international normalized ratio, 2.0 to 3.0) in 18,201 patients with atrial fibrillation and at least one additional risk factor for stroke. The primary outcome was ischemic or hemorrhagic stroke or systemic embolism. The trial was designed to test for noninferiority, with key secondary objectives of testing for superiority with respect to the primary outcome and to the rates of major bleeding and death from any cause.
  
  
  RESULTS
  The median duration of follow-up was 1.8 years. The rate of the primary outcome was 1.27% per year in the apixaban group, as compared with 1.60% per year in the warfarin group (hazard ratio with apixaban, 0.79; 95% confidence interval [CI], 0.66 to 0.95; P<0.001 for noninferiority; P=0.01 for superiority). The rate of major bleeding was 2.13% per year in the apixaban group, as compared with 3.09% per year in the warfarin group (hazard ratio, 0.69; 95% CI, 0.60 to 0.80; P<0.001), and the rates of death from any cause were 3.52% and 3.94%, respectively (hazard ratio, 0.89; 95% CI, 0.80 to 0.99; P=0.047). The rate of hemorrhagic stroke was 0.24% per year in the apixaban group, as compared with 0.47% per year in the warfarin group (hazard ratio, 0.51; 95% CI, 0.35 to 0.75; P<0.001), and the rate of ischemic or uncertain type of stroke was 0.97% per year in the apixaban group and 1.05% per year in the warfarin group (hazard ratio, 0.92; 95% CI, 0.74 to 1.13; P=0.42).
  
  
  CONCLUSIONS
  In patients with atrial fibrillation, apixaban was superior to warfarin in preventing stroke or systemic embolism, caused less bleeding, and resulted in lower mortality. (Funded by Bristol-Myers Squibb and Pfizer; ARISTOTLE ClinicalTrials.gov number, NCT00412984.).
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, NC 27715, USA. christopher.granger@duke.edu
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Granger
authors.forename: John H
authors.initials: JH
authors.lastname: Alexander
authors.forename: John J V
authors.initials: JJ
authors.lastname: McMurray
authors.forename: Renato D
authors.initials: RD
authors.lastname: Lopes
authors.forename: Elaine M
authors.initials: EM
authors.lastname: Hylek
authors.forename: Michael
authors.initials: M
authors.lastname: Hanna
authors.forename: Hussein R
authors.initials: HR
authors.lastname: Al-Khalidi
authors.forename: Jack
authors.initials: J
authors.lastname: Ansell
authors.forename: Dan
authors.initials: D
authors.lastname: Atar
authors.forename: Alvaro
authors.initials: A
authors.lastname: Avezum
authors.forename: M Cecilia
authors.initials: MC
authors.lastname: Bahit
authors.forename: Rafael
authors.initials: R
authors.lastname: Diaz
authors.forename: J Donald
authors.initials: JD
authors.lastname: Easton
authors.forename: Justin A
authors.initials: JA
authors.lastname: Ezekowitz
authors.forename: Greg
authors.initials: G
authors.lastname: Flaker
authors.forename: David
authors.initials: D
authors.lastname: Garcia
authors.forename: Margarida
authors.initials: M
authors.lastname: Geraldes
authors.forename: Bernard J
authors.initials: BJ
authors.lastname: Gersh
authors.forename: Sergey
authors.initials: S
authors.lastname: Golitsyn
authors.forename: Shinya
authors.initials: S
authors.lastname: Goto
authors.forename: Antonio G
authors.initials: AG
authors.lastname: Hermosillo
authors.forename: Stefan H
authors.initials: SH
authors.lastname: Hohnloser
authors.forename: John
authors.initials: J
authors.lastname: Horowitz
authors.forename: Puneet
authors.initials: P
authors.lastname: Mohan
authors.forename: Petr
authors.initials: P
authors.lastname: Jansky
authors.forename: Basil S
authors.initials: BS
authors.lastname: Lewis
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Lopez-Sendon
authors.forename: Prem
authors.initials: P
authors.lastname: Pais
authors.forename: Alexander
authors.initials: A
authors.lastname: Parkhomenko
authors.forename: Freek W A
authors.initials: FW
authors.lastname: Verheugt
authors.forename: Jun
authors.initials: J
authors.lastname: Zhu
authors.forename: Lars
authors.initials: L
authors.lastname: Wallentin
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000150:complications / Q000188:drug therapy*; D004311:Double-Blind Method; D065427:Factor Xa Inhibitors; D005260:Female; D005500:Follow-Up Studies; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D019934:International Normalized Ratio; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011720:Pyrazoles / Q000009:adverse effects / Q000627:therapeutic use*; D011728:Pyridones / Q000009:adverse effects / Q000627:therapeutic use*; D020521:Stroke / Q000517:prevention & control*; D013923:Thromboembolism / Q000517:prevention & control*; D016896:Treatment Outcome; D014859:Warfarin / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D011720:Pyrazoles; D011728:Pyridones; C522181:apixaban; D014859:Warfarin