title: Apixaban versus warfarin in patients with atrial fibrillation according to prior warfarin use: results from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation trial.
abstract: BACKGROUND
  Patients with atrial fibrillation who are vitamin K antagonist (VKA)-naive may have a higher risk of thrombosis and/or bleeding than VKA-experienced patients.
  
  
  RESULTS
  Using data from ARISTOTLE, we assessed baseline characteristics and the treatment effect of apixaban versus warfarin in the VKA-naive and VKA-experienced cohorts. We compared rates of study drug discontinuation and time-in-therapeutic range. Overall, 7,800 (43%) were VKA naive, and 10,401 were VKA experienced. At baseline, both groups were similar with respect to age and congestive heart failure, hypertension, age, diabetes, stroke score (CHADS2). Fewer VKA-naive patients had a history of prior stroke (18% vs 21%) or prior bleeding (10% vs 22%) and were more often female (39% vs 33%). The effect of apixaban on the primary efficacy and safety outcomes was similar in VKA-naive (stroke/systemic embolism: hazard ratio [HR] 0.86, 95% CI 0.67-1.11 and major bleeding: HR 0.73, 95% CI 0.59-0.91) and VKA-experienced populations (stroke/systemic embolism: HR 0.73, 95% CI 0.57-0.95, P value for interaction = 0.39 and major bleeding: HR 0.66, 95% CI 0.55-0.80, P value for interaction = 0.50). Permanent study drug discontinuation was numerically less likely in patients receiving apixaban whether they were VKA naive (HR for discontinuation: 0.87, 95% CI 0.79-0.95) or VKA experienced (HR for discontinuation: 0.93, 95% CI 0.85-1.02). Among patients receiving warfarin, the mean/median times in therapeutic range were lower in the VKA-naive group (VKA-naive: 57.5/61.4, VKA-experienced: 66.0/69.1, P < .001).
  
  
  CONCLUSIONS
  The treatment effects of apixaban (vs warfarin) were not modified by VKA naivety. The rates of stroke/systemic embolism and major bleeding were numerically lower among the patients assigned to apixaban, irrespective of prior VKA use.
authors.affiliation: Division of Hematology, University of Washington, Seattle, WA. Electronic address: davidg99@u.washington.edu.
authors.forename: David A
authors.initials: DA
authors.lastname: Garcia
authors.forename: Lars
authors.initials: L
authors.lastname: Wallentin
authors.forename: Renato D
authors.initials: RD
authors.lastname: Lopes
authors.forename: Laine
authors.initials: L
authors.lastname: Thomas
authors.forename: John H
authors.initials: JH
authors.lastname: Alexander
authors.forename: Elaine M
authors.initials: EM
authors.lastname: Hylek
authors.forename: Jack
authors.initials: J
authors.lastname: Ansell
authors.forename: Michael
authors.initials: M
authors.lastname: Hanna
authors.forename: Fernando
authors.initials: F
authors.lastname: Lanas
authors.forename: Greg
authors.initials: G
authors.lastname: Flaker
authors.forename: Patrick
authors.initials: P
authors.lastname: Commerford
authors.forename: Denis
authors.initials: D
authors.lastname: Xavier
authors.forename: Dragos
authors.initials: D
authors.lastname: Vinereanu
authors.forename: Hongqiu
authors.initials: H
authors.lastname: Yang
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Granger
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000150:complications / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D005343:Fibrinolytic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D006470:Hemorrhage / Q000139:chemically induced* / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011720:Pyrazoles / Q000009:adverse effects / Q000627:therapeutic use*; D011728:Pyridones / Q000009:adverse effects / Q000627:therapeutic use*; D020521:Stroke / Q000188:drug therapy* / Q000517:prevention & control; D013923:Thromboembolism / Q000188:drug therapy* / Q000517:prevention & control; D016896:Treatment Outcome; D014859:Warfarin / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000925:Anticoagulants; D005343:Fibrinolytic Agents; D011720:Pyrazoles; D011728:Pyridones; C522181:apixaban; D014859:Warfarin