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

Am Heart J. 2013 Sep;166(3):549-58. doi: 10.1016/j.ahj.2013.05.016. Epub 2013 Jul 25.

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.

Methods and 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).

Conclusion: 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.

Trial registration: ClinicalTrials.gov NCT00412984.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Anticoagulants / adverse effects
  • Anticoagulants / therapeutic use*
  • Atrial Fibrillation / complications
  • Atrial Fibrillation / drug therapy*
  • Double-Blind Method
  • Female
  • Fibrinolytic Agents / adverse effects
  • Fibrinolytic Agents / therapeutic use*
  • Hemorrhage / chemically induced*
  • Hemorrhage / epidemiology
  • Humans
  • Male
  • Middle Aged
  • Pyrazoles / adverse effects
  • Pyrazoles / therapeutic use*
  • Pyridones / adverse effects
  • Pyridones / therapeutic use*
  • Stroke / drug therapy*
  • Stroke / prevention & control
  • Thromboembolism / drug therapy*
  • Thromboembolism / prevention & control
  • Treatment Outcome
  • Warfarin / adverse effects
  • Warfarin / therapeutic use*

Substances

  • Anticoagulants
  • Fibrinolytic Agents
  • Pyrazoles
  • Pyridones
  • apixaban
  • Warfarin

Associated data

  • ClinicalTrials.gov/NCT00412984