What is the efficacy of Apixaban (apixaban) in preventing stroke and systemic embolism in patients with atrial fibrillation?

Apixaban Efficacy for Stroke Prevention in Atrial Fibrillation

Apixaban 5 mg twice daily is superior to warfarin for preventing stroke and systemic embolism in patients with nonvalvular atrial fibrillation, reducing these events by 21% while simultaneously decreasing major bleeding by 31% and all-cause mortality by 11%. 1, 2, 3

Primary Efficacy Evidence

The ARISTOTLE trial provides the strongest evidence for apixaban's efficacy, demonstrating clear superiority over warfarin across multiple critical outcomes: 1

• Stroke/systemic embolism reduction: 1.27% per year with apixaban versus 1.60% per year with warfarin (HR 0.79,95% CI 0.66-0.95, P=0.01 for superiority) 2, 3
• Major bleeding reduction: 2.13% per year versus 3.09% per year (HR 0.69,95% CI 0.60-0.80) 1
• Intracranial hemorrhage reduction: 0.24% per year versus 0.47% per year (HR 0.50,95% CI 0.31-0.79) 1
• All-cause mortality reduction: 11% relative risk reduction (P=0.046), primarily driven by reduced cardiovascular and stroke deaths 2, 3

This represents a number needed to treat of 303 patients to prevent one stroke or systemic embolism event. 1

Efficacy Compared to Aspirin

For patients unsuitable for warfarin therapy, apixaban demonstrates even more dramatic superiority over aspirin: 1, 4

• Stroke/systemic embolism reduction: 55% relative risk reduction (1.6% per year versus 3.7% per year; HR 0.45,95% CI 0.32-0.62) 1, 2
• Absolute risk reduction: Prevents 2 strokes per 100 patient-years compared to aspirin 4
• Major bleeding: Nearly identical rates (1.4% per year with apixaban versus 1.2% per year with aspirin), demonstrating no safety penalty for the superior efficacy 1, 4, 2
• Number needed to treat: Only 48 patients to prevent one stroke or systemic embolism 1

The AVERROES trial was terminated early due to overwhelming efficacy favoring apixaban. 1, 2

Consistency Across Patient Subgroups

The efficacy of apixaban remains consistent regardless of baseline stroke risk, prior stroke history, renal function, age, weight, or geographic region. 2

Key subgroup findings include: 1, 2

• Primary prevention (no prior stroke/TIA): HR 0.82 (95% CI 0.65-1.03) for stroke/systemic embolism, with particularly strong reduction in intracranial hemorrhage (HR 0.44,95% CI 0.30-0.66) 1
• Renal impairment (CrCl 30-50 mL/min): Consistent efficacy with even greater bleeding reduction in patients with more advanced renal dysfunction 1
• Stage III chronic kidney disease: 68% reduction in stroke/systemic embolism versus aspirin (HR 0.32,95% CI 0.18-0.55) without increased major bleeding 5
• CHADS₂ score: Benefit maintained across all risk strata from 0-1 to 3-6 1

Mechanism of Superior Efficacy

The superior efficacy profile stems from apixaban's balanced reduction in both ischemic and hemorrhagic stroke: 1

• Hemorrhagic stroke reduction: Substantial decrease compared to warfarin (0.24% versus 0.47% per year) 1
• Ischemic stroke: Modest but consistent reduction (0.97% versus 1.05% per year) 1
• Cardioembolic stroke prevention: More effective than aspirin because cardioembolic strokes (the predominant type in atrial fibrillation) are more disabling and apixaban specifically targets this mechanism 4

Clinical Implications for Practice

Apixaban should be the preferred anticoagulant for most patients with nonvalvular atrial fibrillation requiring stroke prevention, given its triple benefit of superior efficacy, reduced bleeding, and lower mortality compared to warfarin. 1, 3

The standard 5 mg twice daily dose applies to the majority of patients, with dose reduction to 2.5 mg twice daily only when patients meet at least 2 of these criteria: age ≥80 years, weight ≤60 kg, or serum creatinine ≥1.5 mg/dL. 1, 6, 7

Common Pitfalls to Avoid

• Inappropriate dose reduction: Approximately 60% of patients receiving reduced-dose apixaban in clinical practice do not meet labeling criteria, potentially compromising stroke prevention efficacy 8
• Assuming aspirin is safer: The AVERROES trial definitively showed similar major bleeding rates between apixaban and aspirin, making aspirin's inferior efficacy unjustifiable in patients who can tolerate apixaban 4
• Discontinuation without bridging: A black box warning exists for increased stroke risk after apixaban cessation; coverage with another anticoagulant should be strongly considered unless pathological bleeding occurs 1
• Combining with antiplatelet therapy: Adding aspirin to apixaban increases bleeding without clear stroke benefit in most atrial fibrillation patients 1, 6