title: Apixaban in patients with atrial fibrillation.
abstract: BACKGROUND
  Vitamin K antagonists have been shown to prevent stroke in patients with atrial fibrillation. However, many patients are not suitable candidates for or are unwilling to receive vitamin K antagonist therapy, and these patients have a high risk of stroke. Apixaban, a novel factor Xa inhibitor, may be an alternative treatment for such patients.
  
  
  METHODS
  In a double-blind study, we randomly assigned 5599 patients with atrial fibrillation who were at increased risk for stroke and for whom vitamin K antagonist therapy was unsuitable to receive apixaban (at a dose of 5 mg twice daily) or aspirin (81 to 324 mg per day), to determine whether apixaban was superior. The mean follow up period was 1.1 years. The primary outcome was the occurrence of stroke or systemic embolism.
  
  
  RESULTS
  Before enrollment, 40% of the patients had used a vitamin K antagonist. The data and safety monitoring board recommended early termination of the study because of a clear benefit in favor of apixaban. There were 51 primary outcome events (1.6% per year) among patients assigned to apixaban and 113 (3.7% per year) among those assigned to aspirin (hazard ratio with apixaban, 0.45; 95% confidence interval [CI], 0.32 to 0.62; P<0.001). The rates of death were 3.5% per year in the apixaban group and 4.4% per year in the aspirin group (hazard ratio, 0.79; 95% CI, 0.62 to 1.02; P=0.07). There were 44 cases of major bleeding (1.4% per year) in the apixaban group and 39 (1.2% per year) in the aspirin group (hazard ratio with apixaban, 1.13; 95% CI, 0.74 to 1.75; P=0.57); there were 11 cases of intracranial bleeding with apixaban and 13 with aspirin. The risk of a first hospitalization for cardiovascular causes was reduced with apixaban as compared with aspirin (12.6% per year vs. 15.9% per year, P<0.001). The treatment effects were consistent among important subgroups.
  
  
  CONCLUSIONS
  In patients with atrial fibrillation for whom vitamin K antagonist therapy was unsuitable, apixaban reduced the risk of stroke or systemic embolism without significantly increasing the risk of major bleeding or intracranial hemorrhage. (Funded by Bristol-Myers Squibb and Pfizer; ClinicalTrials.gov number, NCT00496769.).
authors.affiliation: Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, ON, Canada. stuart.connolly@phri.ca
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Connolly
authors.forename: John
authors.initials: J
authors.lastname: Eikelboom
authors.forename: Campbell
authors.initials: C
authors.lastname: Joyner
authors.forename: Hans-Christoph
authors.initials: HC
authors.lastname: Diener
authors.forename: Robert
authors.initials: R
authors.lastname: Hart
authors.forename: Sergey
authors.initials: S
authors.lastname: Golitsyn
authors.forename: Greg
authors.initials: G
authors.lastname: Flaker
authors.forename: Alvaro
authors.initials: A
authors.lastname: Avezum
authors.forename: Stefan H
authors.initials: SH
authors.lastname: Hohnloser
authors.forename: Rafael
authors.initials: R
authors.lastname: Diaz
authors.forename: Mario
authors.initials: M
authors.lastname: Talajic
authors.forename: Jun
authors.initials: J
authors.lastname: Zhu
authors.forename: Prem
authors.initials: P
authors.lastname: Pais
authors.forename: Andrzej
authors.initials: A
authors.lastname: Budaj
authors.forename: Alexander
authors.initials: A
authors.lastname: Parkhomenko
authors.forename: Petr
authors.initials: P
authors.lastname: Jansky
authors.forename: Patrick
authors.initials: P
authors.lastname: Commerford
authors.forename: Ru San
authors.initials: RS
authors.lastname: Tan
authors.forename: Kui-Hian
authors.initials: KH
authors.lastname: Sim
authors.forename: Basil S
authors.initials: BS
authors.lastname: Lewis
authors.forename: Walter
authors.initials: W
authors.lastname: Van Mieghem
authors.forename: Gregory Y H
authors.initials: GY
authors.lastname: Lip
authors.forename: Jae Hyung
authors.initials: JH
authors.lastname: Kim
authors.forename: Fernando
authors.initials: F
authors.lastname: Lanas-Zanetti
authors.forename: Antonio
authors.initials: A
authors.lastname: Gonzalez-Hermosillo
authors.forename: Antonio L
authors.initials: AL
authors.lastname: Dans
authors.forename: Muhammad
authors.initials: M
authors.lastname: Munawar
authors.forename: Martin
authors.initials: M
authors.lastname: O'Donnell
authors.forename: John
authors.initials: J
authors.lastname: Lawrence
authors.forename: Gayle
authors.initials: G
authors.lastname: Lewis
authors.forename: Rizwan
authors.initials: R
authors.lastname: Afzal
authors.forename: Salim
authors.initials: S
authors.lastname: Yusuf
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001241:Aspirin / 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*; D065427:Factor Xa Inhibitors; D005260:Female; D005343:Fibrinolytic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011720:Pyrazoles / Q000009:adverse effects / Q000627:therapeutic use*; D011728:Pyridones / Q000009:adverse effects / Q000627:therapeutic use*; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology / Q000517:prevention & control*
chemical_list: D065427:Factor Xa Inhibitors; D005343:Fibrinolytic Agents; D011720:Pyrazoles; D011728:Pyridones; C522181:apixaban; D001241:Aspirin