AVERROES

Apixaban VERsus acetylsalicylic acid [ASA] to prevent StROke in atrial fibrillation PatiEntS who have failed or are unsuitable for vitamin K antagonist treatment (2011)

Condition

Prevention of ischemic or hemorrhagic stroke in AF

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Objective

To evaluate the safety and efficacy of apixaban versus acetylsalicylic acid (ASA) in preventing strokes in subjects with AF and at least one additional stroke risk factor, who are not suitable for vitamin K antagonist treatment

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Trial design

Randomized, double-blind phase III study
Active treatment: apixaban 5 mg p.o. twice daily for up to 36 months or end of study (n=2808)
Control treatment: ASA (81–324 mg once daily) for up to 36 months or end of study (n=2791)

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Endpoints

Primary efficacy endpoint: time (days) from first dose of study drug to first occurrence of unrefuted ischemic stroke, hemorrhagic stroke or systemic embolism
Primary safety endpoint: occurrence of major bleeding
Other outcome measures: occurrence of myocardial infarction, death from vascular causes, and death from any cause, as well as of composites of major vascular events

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Trial participants

5599 patients ≥50 years of age with atrial fibrillation and increased risk for stroke (presence of at least one risk factor), who are not suitable for vitamin K antagonist therapy

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Results

Efficacy outcome: The data and safety monitoring board recommended early termination of the study because of a clear treatment benefit in favor of apixaban for the primary outcome that exceeded 4 SD. After a mean duration of follow-up of 1.1 years there were 51 primary outcome events (1.6% per year) in patients assigned to apixaban (n=2808) and 113 (3.7% per year) in patients assigned to ASA (n=2791) (absolute risk reduction with apixaban 2.1%, relative risk reduction 55%; p<0.001)
Safety outcome: There were 44 major bleeding events (1.4% per year) among patients taking apixaban and 39 (1.2% per year) among those taking ASA (p=0.57). Significantly fewer patients in the apixaban group than in the ASA group had a serious adverse event (22% vs. 27%, p<0.001)

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Summary

Efficacy: Oral apixaban was superior to aspirin in preventing

  • Stroke or systemic embolism
  • Stroke, systemic embolism or death
  • Stroke, systemic embolism, myocardial infarction, death from vascular cause, or major bleeding event
  • Stroke
  • Systemic embolism
  • Hospitalisation for cardiovascular cause 

Safety: 

  • No difference in major, intracranial, clinically relevant non-major and minor bleeding
  • Significantly less severe adverse events in the apixaban group

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Reference

Connolly SJ, Eikelboom J, Campbell Joyner BS, Diener HC, Hart R, Golitsyn S, Flaker G, Avezum A, Hohnloser SH, Diaz R, Talajic M, Zhu J, Pais P, Budaj A, Parkhomenko A, Jansky P, Commerford P, Tan RS, Sim KH, Lewis BS, Van Mieghem W, Lip GYH, Kim JH, Lanas-Zanetti F, Gonzalez-Hermosillo A, Dans AL, Munawar M, O’Donnell M, Lawrence J, Lewis G, Afzal R, Yusuf S, for the AVERROES Steering Committee and Investigators. Apixaban in patients with atrial fibrillation. N Engl J Med 2011;364:806-817

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Corresponding author

Dr. Stuart J. Connolly, Population Health Research Institute, 237 Barton St. E., Hamilton, ON L8L 2X2, Canada, e-mail: stuart.connolly@phri.ca

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