title: Major bleeding in patients with atrial fibrillation receiving apixaban or warfarin: The ARISTOTLE Trial (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation): Predictors, Characteristics, and Clinical Outcomes.
abstract: OBJECTIVE
  This study sought to characterize major bleeding on the basis of the components of the major bleeding definition, to explore major bleeding by location, to define 30-day mortality after a major bleeding event, and to identify factors associated with major bleeding.
  
  
  BACKGROUND
  Apixaban was shown to reduce the risk of major hemorrhage among patients with atrial fibrillation in the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial.
  
  
  METHODS
  All patients who received at least 1 dose of a study drug were included. Major bleeding was defined according to the criteria of the International Society on Thrombosis and Haemostasis. Factors associated with major hemorrhage were identified using a multivariable Cox model.
  
  
  RESULTS
  The on-treatment safety population included 18,140 patients. The rate of major hemorrhage among patients in the apixaban group was 2.13% per year compared with 3.09% per year in the warfarin group (hazard ratio [HR] 0.69, 95% confidence interval [CI]: 0.60 to 0.80; p < 0.001). Compared with warfarin, major extracranial hemorrhage associated with apixaban led to reduced hospitalization, medical or surgical intervention, transfusion, or change in antithrombotic therapy. Major hemorrhage followed by mortality within 30 days occurred half as often in apixaban-treated patients than in those receiving warfarin (HR 0.50, 95% CI: 0.33 to 0.74; p < 0.001). Older age, prior hemorrhage, prior stroke or transient ischemic attack, diabetes, lower creatinine clearance, decreased hematocrit, aspirin therapy, and nonsteroidal anti-inflammatory drugs were independently associated with an increased risk.
  
  
  CONCLUSIONS
  Apixaban, compared with warfarin, was associated with fewer intracranial hemorrhages, less adverse consequences following extracranial hemorrhage, and a 50% reduction in fatal consequences at 30 days in cases of major hemorrhage.
authors.affiliation: Boston University Medical Center, Boston, Massachusetts. Electronic address: ehylek@bu.edu.
authors.forename: Elaine M
authors.initials: EM
authors.lastname: Hylek
authors.affiliation: Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
authors.forename: Claes
authors.initials: C
authors.lastname: Held
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina.
authors.forename: John H
authors.initials: JH
authors.lastname: Alexander
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina.
authors.forename: Renato D
authors.initials: RD
authors.lastname: Lopes
authors.affiliation: G. d'Annunzio University, Chieti, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: De Caterina
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Wojdyla
authors.affiliation: Wilhelminen Hospital, Vienna, Austria.
authors.forename: Kurt
authors.initials: K
authors.lastname: Huber
authors.affiliation: Motol University Hospital, Prague, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Jansky
authors.affiliation: Hôpital Bichat-Claude Bernard, Paris, France.
authors.forename: Philippe Gabriel
authors.initials: PG
authors.lastname: Steg
authors.affiliation: Bristol-Myers Squibb, Princeton, New Jersey.
authors.forename: Michael
authors.initials: M
authors.lastname: Hanna
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina.
authors.forename: Laine
authors.initials: L
authors.lastname: Thomas
authors.affiliation: Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Wallentin
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina.
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Granger
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects; D001281:Atrial Fibrillation / Q000150:complications / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D014943:Global Health; D006470:Hemorrhage / Q000139:chemically induced* / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011720:Pyrazoles / Q000008:administration & dosage* / Q000009:adverse effects; D011728:Pyridones / Q000008:administration & dosage* / Q000009:adverse effects; D012189:Retrospective Studies; D020521:Stroke / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control*; D015996:Survival Rate / Q000639:trends; D013923:Thromboembolism / Q000150:complications / Q000517:prevention & control*; D014859:Warfarin / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D000925:Anticoagulants; D011720:Pyrazoles; D011728:Pyridones; C522181:apixaban; D014859:Warfarin
keywords: atrial fibrillation; bleeding; factor Xa inhibitor