Apixaban Benefits A-fib Patients Regardless of Previous Warfarin Use

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Key Points:
  • ARISTOTLE analysis investigates outcomes with apixaban by prior warfarin use
  • A-fib patients randomized to apixaban had less stroke/systemic embolism regardless of previous warfarin exposure
  • Findings similar to RE-LY subanalysis, which showed dabigatran effectiveness regardless of prior warfarin use

By Jason Kahn
Monday, August 05, 2013

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The novel oral anticoagulant apixaban has similar effects on stroke, systemic embolism and major bleeding in patients with atrial fibrillation (A-fib) whether they have been on previous warfarin therapy or not, according to a subanalysis of the ARISTOTLE trial published online July 26, 2013, ahead of print in the American Heart Journal.

ARISTOTLE (Apixaban for Reduction In STroke and Other ThromboemboLic Events in atrial fibrillation) randomized 18,201 patients with A-fib and at least 1 stroke risk factor to dose-adjusted warfarin plus placebo or the oral factor Xa inhibitor apixaban (5 mg [2.5 mg for those at high bleeding risk] twice daily) plus placebo. Apixaban proved superior to warfarin for preventing stroke or systemic embolism, the primary endpoint.

For the subanalysis, David Garcia, MD, of the University of Washington (Seattle, WA), and colleagues assessed the ARISTOTLE results according to whether patients were warfarin naive or not prior to study enrollment. This was done due to the observation from retrospective studies that patients with little or no exposure to anticoagulation may be at higher risk of adverse outcomes than patients who have been on such therapy previously.

In ARISTOTLE, less than half (42.9%) of patients were warfarin naive prior to study enrollment. Compared with patients randomized to warfarin, those receiving apixaban had numerically lower rates of stroke/systemic embolism and other endpoints regardless of prior warfarin use (table 1).

Table 1. Outcomes by Prior Warfarin Use (Per 100 Patient Years)




HR 95% CI

Stroke/Systemic Embolism
Warfarin Naive
Warfarin Experienced



 0.86 (0.67-1.11)
0.73 (0.57-0.95)

Major Bleeding
Warfarin Naive
Warfarin Experienced



 0.73 (0.59-0.91)
0.66 (0.55-0.80)

Intracranial Bleeding
Warfarin Naive
Warfarin Experienced



 0.60 (0.38-0.93)
0.28 (0.17-0.46)

Warfarin Naive
Warfarin Experienced



 0.91 (0.78-1.06)
0.88 (0.76-1.03)

Warfarin Naive
Warfarin Experienced



 0.87 (0.79-0.95)
0.93 (0.85-1.02)

Among all warfarin treated patients, the median percent time in therapeutic range (TTR) in ARISTOTLE was 66%—61.4% in those who were warfarin naive and 69.1% in those who had previously received warfarin (P < 0.001). During the first 90 days, the corresponding median TTRs were 43.7% and 54.9%, respectively (P < 0.001). The difference in TTR between warfarin-naive and warfarin-experienced patients was most noticeable in the subtherapeutic range (INR < 2.0).

“In the present prospective comparison, prior [warfarin] exposure did not modify the effect of apixaban relative to warfarin for most key efficacy and safety outcomes,” the authors conclude, adding that the results were similar to a subanalysis of the RE-LY trial, which found no interaction between lack of previous warfarin therapy and the effects of dabigatran vs. warfarin.

Similar to that trial, the current one suggests “that [warfarin] naivety should not impact decisions about whether to use apixaban or warfarin in clinical practice,” Dr. Garcia and colleagues note, adding that “treatment with apixaban as compared with warfarin will, in patients with [A-fib] and a raised risk for stroke, be associated with lower rates of stroke/systemic embolism and major bleeding both in patients switching from [warfarin] as well as in patients starting oral anticoagulation.”


Garcia DA, Wallentin L, Lopes RD, et al. 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;Epub ahead of print.



  • ARISTOTLE was funded by Bristol-Myers Squibb and Pfizer.
  • Dr. Garcia reports receiving consulting fees from Boehringer-Ingelheim, Bristol-Myers Squibb, and Daiichi Sankyo and payments from Boehringer-Ingelheim for developing educational presentations.


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