title: Direct Comparison of Dabigatran, Rivaroxaban, and Apixaban for Effectiveness and Safety in Nonvalvular Atrial Fibrillation.
abstract: BACKGROUND
  The introduction of non-vitamin K antagonist oral anticoagulants (NOACs) has been a major advance for stroke prevention in atrial fibrillation (AF). Patients and clinicians now have a choice between different NOACs, but there is no direct comparative effectiveness evidence to guide decision-making. We aimed to compare the effectiveness and safety of dabigatran, rivaroxaban, and apixaban in clinical practice.
  
  
  METHODS
  Using a large US administrative claims database, we created three one-to-one propensity-score-matched cohorts of patients with nonvalvular AF who were users of dabigatran, rivaroxaban, or apixaban between October 1, 2010 and February 28, 2015 (rivaroxaban vs dabigatran, n = 31,574; apixaban vs dabigatran, n = 13,084; and apixaban vs rivaroxaban, n = 13,130). The primary outcomes were stroke and systemic embolism (effectiveness) and major bleeding (safety) that occurred during treatment. Cox proportional hazards models were used to compare outcomes in propensity-score-matched cohorts.
  
  
  RESULTS
  We found no differences between the three NOACs in the risk of stroke or systemic embolism (hazard ratio [HR], 1.00; 95% CI, 0.75-1.32 for rivaroxaban vs dabigatran; HR, 0.82; 95% CI, 0.51-1.31 for apixaban vs dabigatran; and HR, 1.05; 95% CI, 0.64-1.72 for apixaban vs rivaroxaban). Apixaban was associated with a lower risk of major bleeding (HR, 0.50; 95% CI, 0.36-0.70; P < .001 vs dabigatran and HR, 0.39; 95% CI, 0.28-0.54; P < .001 vs rivaroxaban). Rivaroxaban was associated with an increased risk of major bleeding (HR, 1.30; 95% CI, 1.10-1.53; P < .01) and intracranial bleeding (HR, 1.79; 95% CI, 1.12-2.86; P < .05) compared with dabigatran.
  
  
  CONCLUSIONS
  Dabigatran, rivaroxaban, and apixaban appear to have similar effectiveness, although apixaban may be associated with a lower bleeding risk and rivaroxaban may be associated with an elevated bleeding risk.
authors.affiliation: Cardiovascular Diseases, Mayo Clinic, Rochester, MN; Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN. Electronic address: noseworthy.peter@mayo.edu.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Noseworthy
authors.affiliation: Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN.
authors.forename: Xiaoxi
authors.initials: X
authors.lastname: Yao
authors.affiliation: Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN; Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Scottsdale, AZ; Division of Health Care Policy and Research, Department of Health Services Research, Rochester, MN.
authors.forename: Neena S
authors.initials: NS
authors.lastname: Abraham
authors.affiliation: Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN.
authors.forename: Lindsey R
authors.initials: LR
authors.lastname: Sangaralingham
authors.affiliation: Cardiovascular Diseases, Mayo Clinic, Rochester, MN; Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN.
authors.forename: Robert D
authors.initials: RD
authors.lastname: McBane
authors.affiliation: Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN; Division of Health Care Policy and Research, Department of Health Services Research, Rochester, MN; Optum Labs, Cambridge, MA.
authors.forename: Nilay D
authors.initials: ND
authors.lastname: Shah
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000991:Antithrombins / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000188:drug therapy*; D002543:Cerebral Hemorrhage / Q000139:chemically induced; D000069604:Dabigatran / Q000627:therapeutic use*; D065427:Factor Xa Inhibitors / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D057216:Propensity Score; D011720:Pyrazoles / Q000627:therapeutic use*; D011728:Pyridones / Q000627:therapeutic use*; D012189:Retrospective Studies; D000069552:Rivaroxaban / Q000627:therapeutic use*; D020521:Stroke / Q000517:prevention & control*; D014481:United States
chemical_list: D000991:Antithrombins; D065427:Factor Xa Inhibitors; D011720:Pyrazoles; D011728:Pyridones; C522181:apixaban; D000069552:Rivaroxaban; D000069604:Dabigatran
keywords: atrial fibrillation; bleeding; non-vitamin K antagonist oral anticoagulants; stroke