"Apixaban versus Warfarin in Patients with Atrial Fibrillation".The New England Journal of Medicine. 2011. 365:981-992.

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1Clinical Question 2Bottom Line 3Major Points 4Guidelines 5Design 6Population 6.1Inclusion Criteria 6.2Exclusion Criteria 6.3Baseline Characteristics 7Interventions 8Outcomes 8.1Primary Outcome 8.2Secondary Outcomes 9Funding 10Further Reading

Clinical Question

In patients with atrial fibrillation and at least one additional risk factor for stroke, is apixaban superior to warfarin in preventing stroke or systemic embolism?

Bottom Line

In patients with atrial fibrillation, apixaban is superior to warfarin in preventing stroke or systemic embolism, causes less bleeding, and results in lower mortality.

Major Points

Warfarin, effective in stroke prevention for patients with atrial fibrillation, is limited by its narrow therapeutic range, interactions, and bleeding risk. Apixaban, a factor Xa inhibitor, demonstrates superiority over warfarin in stroke prevention, fewer bleeding events, and reduced mortality.

Guidelines

Current guidelines have not been explicitly adjusted to reflect the results of this trial.

Design

Multicenter, double-blind, parallel-group, randomized, placebo-controlled trial

N=18,201 patients with atrial fibrillation Apixaban 5 mg PO BID (n=9120) Warfarin to INR 2.0-3.0 (n=9081) Setting: 1034 sites in 39 countries Enrollment: 2006-2010 Median follow-up: 1.8 years Analysis: Intention-to-treat Primary Efficacy Outcome: Stroke or systemic embolism Primary Safety Outcome: Major bleeding

Population

Inclusion Criteria Atrial fibrillation/flutter, at least one risk factor for stroke

Exclusion Criteria Reversible atrial fibrillation, moderate/severe mitral stenosis, conditions necessitating anticoagulation, recent stroke, aspirin >165 mg/day, severe renal impairment

Baseline Characteristics Median age: 70 years; 35.3% female; mean CHADS2 score: 2.1

Interventions

Apixaban at a dose of 5 mg BID (2.5 mg BID in a subset) Warfarin with INR target of 2.0-3.0

Outcomes

Primary Outcome Stroke or systemic embolism Apixaban: 1.27% per year Warfarin: 1.60% per year (HR 0.79; 95% CI, 0.66-0.95; P<0.001 for noninferiority; P=0.01 for superiority)

Outcomes

Major bleeding Apixaban: 2.13% per year Warfarin: 3.09% per year (HR 0.69; 95% CI, 0.60-0.80; P<0.001) Death from any cause Apixaban: 3.52% per year Warfarin: 3.94% per year (HR 0.89; 95% CI, 0.80-0.99; P=0.047)

Funding

Bristol-Myers Squibb and Pfizer

Further Reading

For more information, this study is registered on ClinicalTrials.gov, number NCT00412984.