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

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)

Secondary 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.