title: Rivaroxaban versus warfarin in nonvalvular atrial fibrillation.
abstract: BACKGROUND
  The use of warfarin reduces the rate of ischemic stroke in patients with atrial fibrillation but requires frequent monitoring and dose adjustment. Rivaroxaban, an oral factor Xa inhibitor, may provide more consistent and predictable anticoagulation than warfarin.
  
  
  METHODS
  In a double-blind trial, we randomly assigned 14,264 patients with nonvalvular atrial fibrillation who were at increased risk for stroke to receive either rivaroxaban (at a daily dose of 20 mg) or dose-adjusted warfarin. The per-protocol, as-treated primary analysis was designed to determine whether rivaroxaban was noninferior to warfarin for the primary end point of stroke or systemic embolism.
  
  
  RESULTS
  In the primary analysis, the primary end point occurred in 188 patients in the rivaroxaban group (1.7% per year) and in 241 in the warfarin group (2.2% per year) (hazard ratio in the rivaroxaban group, 0.79; 95% confidence interval [CI], 0.66 to 0.96; P<0.001 for noninferiority). In the intention-to-treat analysis, the primary end point occurred in 269 patients in the rivaroxaban group (2.1% per year) and in 306 patients in the warfarin group (2.4% per year) (hazard ratio, 0.88; 95% CI, 0.74 to 1.03; P<0.001 for noninferiority; P=0.12 for superiority). Major and nonmajor clinically relevant bleeding occurred in 1475 patients in the rivaroxaban group (14.9% per year) and in 1449 in the warfarin group (14.5% per year) (hazard ratio, 1.03; 95% CI, 0.96 to 1.11; P=0.44), with significant reductions in intracranial hemorrhage (0.5% vs. 0.7%, P=0.02) and fatal bleeding (0.2% vs. 0.5%, P=0.003) in the rivaroxaban group.
  
  
  CONCLUSIONS
  In patients with atrial fibrillation, rivaroxaban was noninferior to warfarin for the prevention of stroke or systemic embolism. There was no significant between-group difference in the risk of major bleeding, although intracranial and fatal bleeding occurred less frequently in the rivaroxaban group. (Funded by Johnson & Johnson and Bayer; ROCKET AF ClinicalTrials.gov number, NCT00403767.).
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, NC 27705, USA. manesh.patel@duke.edu
authors.forename: Manesh R
authors.initials: MR
authors.lastname: Patel
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Mahaffey
authors.forename: Jyotsna
authors.initials: J
authors.lastname: Garg
authors.forename: Guohua
authors.initials: G
authors.lastname: Pan
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Singer
authors.forename: Werner
authors.initials: W
authors.lastname: Hacke
authors.forename: Günter
authors.initials: G
authors.lastname: Breithardt
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Halperin
authors.forename: Graeme J
authors.initials: GJ
authors.lastname: Hankey
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Piccini
authors.forename: Richard C
authors.initials: RC
authors.lastname: Becker
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Nessel
authors.forename: John F
authors.initials: JF
authors.lastname: Paolini
authors.forename: Scott D
authors.initials: SD
authors.lastname: Berkowitz
authors.forename: Keith A A
authors.initials: KA
authors.lastname: Fox
authors.forename: Robert M
authors.initials: RM
authors.lastname: Califf
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000150:complications / Q000188:drug therapy*; D004311:Double-Blind Method; D004617:Embolism / Q000453:epidemiology / Q000517:prevention & control; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D057194:Intention to Treat Analysis; D008297:Male; D008875:Middle Aged; D009025:Morpholines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000069552:Rivaroxaban; D020521:Stroke / Q000453:epidemiology / Q000517:prevention & control; D013876:Thiophenes / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D014859:Warfarin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000925:Anticoagulants; D009025:Morpholines; D013876:Thiophenes; D014859:Warfarin; D000069552:Rivaroxaban