ARISTOTLE
Apixaban versus warfarin in patients with atrial fibrillation
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Overview
Apixaban beat warfarin for stroke prevention with less major bleeding and lower mortality in atrial fibrillation.
Clinical takeaway
ARISTOTLE established apixaban as a superior alternative to warfarin for most patients with nonvalvular atrial fibrillation, reducing stroke or systemic embolism, major bleeding, and all-cause mortality.
Key result
Stroke/systemic embolism: HR 0.79 (95% CI 0.66-0.95), p=0.01 for superiority.
Practice impact
Helped drive the shift toward DOAC-first anticoagulation in nonvalvular atrial fibrillation.
Evidence
Study design
Randomized, double-blind, active-controlled trial
Enrollment
18,201
Follow-up
Median 1.8 years
Geography
Multinational
Clinical question
In patients with nonvalvular atrial fibrillation and at least one additional risk factor for stroke, is apixaban superior to warfarin for prevention of stroke or systemic embolism?
Population
- Nonvalvular atrial fibrillation
- At least one additional stroke risk factor (CHADS2 >= 1)
Intervention
Apixaban 5 mg twice daily (2.5 mg twice daily if dose-reduction criteria met)
Comparator
Dose-adjusted warfarin (target INR 2-3)
Primary outcome
Stroke or systemic embolism
Apixaban reduced stroke or systemic embolism compared with warfarin.
HR / 0.79 / CI 0.66-0.95 / p=0.01
Key results
- Stroke/systemic embolism: HR 0.79 (95% CI 0.66-0.95), p=0.01 for superiority
- Major bleeding: HR 0.69 (0.60-0.80), p<0.001
- All-cause mortality: HR 0.89 (0.80-0.998), p=0.047
- Intracranial hemorrhage markedly reduced
Harms
- Major bleeding was lower with apixaban than with warfarin.
- Intracranial hemorrhage was markedly reduced.
Clinical Use
When to cite
- When justifying apixaban or DOAC use over warfarin in nonvalvular AF
- When discussing anticoagulation choices for stroke prevention
Practice impact
- Helped establish DOAC-first anticoagulation in nonvalvular AF
- Incorporated into major AF guidelines
- Reduced reliance on warfarin and INR monitoring
Applicability
- Most applicable to patients with nonvalvular AF who need stroke prevention
- Useful when balancing stroke prevention against major bleeding risk
Limitations
- Excluded mechanical heart valves
- Excluded clinically significant mitral stenosis
- Quality of warfarin control varied across sites
Common misinterpretations
- Do not extrapolate DOAC preference to mechanical valves or moderate-to-severe mitral stenosis.
Citation
Granger CB, Alexander JH, McMurray JJ, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365(11):981-992. doi:10.1056/NEJMoa1107039
- PMID
- 21870978