Outcomes of apixaban vs. warfarin by type and duration of atrial fibrillation: results from the ARISTOTLE trial

Eur Heart J. 2013 Aug;34(31):2464-71. doi: 10.1093/eurheartj/eht135. Epub 2013 Apr 17.


Aims: It is uncertain whether the benefit from apixaban varies by type and duration of atrial fibrillation (AF).

Methods and results: A total of 18 201 patients with AF [2786 (15.3%) with paroxysmal and 15 412 (84.7%) with persistent or permanent] were randomized to apixaban or warfarin. In this pre-specified secondary analysis, we compared outcomes and treatment effect of apixaban vs. warfarin by AF type and duration. The primary efficacy endpoint was a composite of ischaemic or haemorrhagic stroke or systemic embolism. The secondary efficacy endpoint was all-cause mortality. There was a consistent reduction in stroke or systemic embolism (P for interaction = 0.71), all-cause mortality (P for interaction = 0.75), and major bleeding (P for interaction = 0.50) with apixaban compared with warfarin for both AF types. Apixaban was superior to warfarin in all studied endpoints, regardless of AF duration at study entry (P for all interactions >0.13). The rate of stroke or systemic embolism was significantly higher in patients with persistent or permanent AF than patients with paroxysmal AF (1.52 vs. 0.98%; P = 0.003, adjusted P = 0.015). There was also a trend towards higher mortality in patients with persistent or permanent AF (3.90 vs. 2.81%; P = 0.0002, adjusted P = 0.066).

Conclusion: The risks of stroke, mortality, and major bleeding were lower with apixaban than warfarin regardless of AF type and duration. Although the risk of stroke or systemic embolism was lower in paroxysmal than persistent or permanent AF, apixaban is an attractive alternative to warfarin in patients with AF and at least one other risk factor for stroke, regardless of the type or duration of AF.

Keywords: Apixaban; Major bleeding; Paroxysmal atrial fibrillation; Permanent atrial fibrillation; Persistent atrial fibrillation; Stroke.

Publication types

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

MeSH terms

  • Aged
  • Anti-Arrhythmia Agents / therapeutic use
  • Anticoagulants / therapeutic use*
  • Atrial Fibrillation / complications*
  • Atrial Fibrillation / mortality
  • Atrial Fibrillation / therapy
  • Catheter Ablation
  • Cause of Death
  • Electric Countershock
  • Electrocardiography
  • Embolism / mortality
  • Embolism / prevention & control
  • Female
  • Hemorrhage / chemically induced
  • Humans
  • Male
  • Pyrazoles / therapeutic use*
  • Pyridones / therapeutic use*
  • Stroke / mortality
  • Stroke / prevention & control*
  • Treatment Outcome
  • Warfarin / therapeutic use*


  • Anti-Arrhythmia Agents
  • Anticoagulants
  • Pyrazoles
  • Pyridones
  • apixaban
  • Warfarin