Stroke Risk Reduction with Apixaban vs Aspirin in Atrial Fibrillation
Apixaban reduces stroke risk by 54% compared to aspirin in patients with atrial fibrillation, preventing approximately 2 strokes per 100 patient-years, with similar major bleeding rates between the two agents. 1
Primary Efficacy Data from AVERROES Trial
The direct comparison trial (AVERROES) enrolled 5,600 patients with atrial fibrillation who were unsuitable for warfarin therapy and demonstrated clear superiority of apixaban over aspirin 1:
Stroke or systemic embolism occurred in 1.6% per year with apixaban vs 3.6% per year with aspirin (relative risk 0.46; 95% CI 0.33-0.64), representing a 54% relative risk reduction 1
The absolute risk reduction translates to preventing 2 strokes per 100 patient-years of treatment 1
Major bleeding rates were nearly identical: 1.4% per year with apixaban vs 1.2% per year with aspirin, demonstrating no significant increase in bleeding risk 1
Stroke Risk Stratification by CHA₂DS₂-VASc Score
The benefit of apixaban over aspirin varies substantially based on baseline stroke risk 2:
For patients with CHA₂DS₂-VASc >4: Apixaban prevents 1.28 strokes/systemic emboli per 100 patient-years while causing only 0.68 additional major bleeds per 100 patient-years—a clearly favorable benefit-risk profile 2
For patients with CHA₂DS₂-VASc <4: Apixaban prevents only 0.12 strokes per 100 patient-years while causing 0.33 additional major bleeds per 100 patient-years—a less compelling benefit 2
For patients with CHA₂DS₂-VASc =4: The benefit-risk balance is intermediate, with 0.32 strokes prevented and 0.28 major bleeds caused per 100 patient-years 2
Special Population: Chronic Kidney Disease
In patients with stage III chronic kidney disease (eGFR 30-60 mL/min), apixaban demonstrates even greater superiority over aspirin 3:
Apixaban reduced stroke by 68% in CKD stage III patients (1.8% per year vs 5.6% per year with aspirin; HR 0.32; 95% CI 0.18-0.55) 3
This compares to a 43% reduction in patients with normal renal function, suggesting CKD patients derive greater benefit from apixaban over aspirin 3
Major bleeding rates remained similar between apixaban and aspirin even in CKD patients (2.5% vs 2.2% per year; HR 1.2; 95% CI 0.65-2.1) 3
Bleeding Risk Comparison
The bleeding profile of apixaban vs aspirin is remarkably similar across multiple parameters 4:
Overall bleeding events (major plus clinically relevant non-major): 4.5% per year with apixaban vs 3.8% per year with aspirin (HR 1.18; 95% CI 0.92-1.51; not significant) 4
Anatomic sites of bleeding did not differ between the two therapies 4
Risk factors for bleeding were identical for both agents, including non-study aspirin use and history of nosebleeds 4
The relative risk of bleeding with apixaban vs aspirin remains constant across all CHADS₂ categories, while the stroke reduction benefit favors apixaban regardless of baseline risk 4
Clinical Context: Aspirin's Limited Efficacy
Understanding aspirin's modest efficacy in atrial fibrillation helps contextualize apixaban's superiority 1:
Aspirin provides only 19% relative risk reduction compared to placebo (95% CI 2%-34%) in atrial fibrillation patients 1
Aspirin is more effective for non-cardioembolic strokes but less effective for the cardioembolic strokes that predominate in atrial fibrillation 1
Cardioembolic strokes are more disabling on average than non-cardioembolic strokes, making aspirin's preferential prevention of less severe strokes clinically less meaningful 1
Mortality Benefit
Beyond stroke prevention, apixaban demonstrates survival advantages not seen with aspirin 5:
In the ARISTOTLE trial comparing apixaban to warfarin, apixaban reduced all-cause mortality by 11% (P = 0.047) 5
This mortality benefit, combined with stroke reduction, represents a meaningful improvement in both morbidity and mortality that aspirin cannot provide 5
Common Pitfalls to Avoid
Do not assume aspirin is "safer" than apixaban—the AVERROES trial definitively showed similar major bleeding rates, making this a false equivalence 1
Do not use aspirin as a substitute for anticoagulation in patients who can tolerate apixaban—the stroke reduction with apixaban is substantially greater with no additional bleeding risk 1
Do not overlook CKD patients—these individuals derive even greater benefit from apixaban over aspirin and should not be denied anticoagulation based on renal concerns alone (if eGFR >15 mL/min) 3
Do not combine apixaban with aspirin routinely—this increases bleeding without providing additional stroke protection in most atrial fibrillation patients 6