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evident
Original paper
2011NEJMCardiology

AVERROES

Apixaban in patients with atrial fibrillation

RCTAtrial fibrillation anticoagulation

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Overview

Apixaban beat aspirin for stroke prevention in AF patients unsuitable for warfarin.

Clinical takeaway

AVERROES is a clean teaching trial: aspirin is not an adequate substitute for anticoagulation when AF stroke risk warrants treatment.

Key result

Stroke or systemic embolism was 1.6%/yr with apixaban vs 3.7%/yr with aspirin (HR 0.45; 95% CI 0.32-0.62), without a significant increase in major bleeding (1.4%/yr vs 1.2%/yr).

Practice impact

DOACs displaced aspirin for AF stroke prevention in eligible patients.

Evidence

Study design

Randomized, double-blind trial stopped early for benefit.

Enrollment

5,599

Follow-up

Mean 1.1 years.

Geography

Multinational

Clinical question

Is apixaban superior to aspirin for preventing stroke or systemic embolism in AF patients unsuitable for warfarin?

Population

  • Patients with atrial fibrillation at increased stroke risk for whom vitamin K antagonist therapy was considered unsuitable.

Intervention

Apixaban 5 mg twice daily, dose-adjusted when indicated.

Comparator

Aspirin 81 to 324 mg daily.

Primary outcome

Stroke or systemic embolism.

Apixaban was superior to aspirin for preventing stroke or systemic embolism in atrial fibrillation.

Hazard ratio / 0.45 / 95% CI 0.32-0.62 / p<0.001

Key results

  • Stroke or systemic embolism: 1.6% per year with apixaban vs 3.7% per year with aspirin; HR 0.45 (95% CI 0.32-0.62; p<0.001).
  • Major bleeding was not significantly increased: 1.4% vs 1.2% per year; HR 1.13 (95% CI 0.74-1.75; p=0.57); intracranial bleeding 11 vs 13 cases.
  • Death: 3.5% vs 4.4% per year; HR 0.79 (95% CI 0.62-1.02; p=0.07).
  • The trial was stopped early because of clear benefit.

Harms

  • Bleeding remains the major practical concern with any anticoagulant.
  • Dose adjustment and renal function assessment are needed.

Clinical Use

Practice impact

  • Helped end aspirin's role as a default alternative for AF stroke prevention when anticoagulation is indicated.

Applicability

  • AF patients at elevated stroke risk who are candidates for apixaban but not warfarin.

Limitations

  • Warfarin-unsuitable population; ARISTOTLE answers apixaban versus warfarin.
  • Early stopping can magnify apparent benefit.

Common misinterpretations

  • Do not use aspirin for AF stroke prevention simply because it feels safer; it is much less effective.

Related evidence

ARISTOTLE - Later TrialROCKET AF - Similar Question

Citation

Connolly SJ, Eikelboom J, Joyner C, et al. Apixaban in patients with atrial fibrillation. N Engl J Med. 2011;364(9):806-817. doi:10.1056/NEJMoa1007432

There were 51 primary outcome events (1.6% per year) among patients assigned to apixaban and 113 (3.7% per year) among those assigned to aspirin (hazard ratio with apixaban, 0.45; 95% confidence interval [CI], 0.32 to 0.62; P<0.001).