Efficacy of apixaban when compared with warfarin in relation to renal function in patients with atrial fibrillation: insights from the ARISTOTLE trial
Open accessAbstract
AIMS: Atrial fibrillation (AF) is common among patients with impaired renal function. Apixaban, a novel oral anticoagulant with partial renal excretion, was compared with warfarin and reduced the rate stroke, death and bleeding in the ARISTOTLE trial. We evaluated these outcomes in relation to renal function. METHODS AND RESULTS: Baseline glomerular filtration rate (GFR) was estimated using the Cockcroft-Gault and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations as well as cystatin C measurements. According to baseline Cockcroft-Gault, there were 7518 patients (42%) with an estimated GFR (eGFR) of >80 mL/min, 7587 (42%) between >50 and 80 mL/min, and 3017 (15%) with an eGFR of ≤50 mL/min. The rate of cardiovascular events and bleeding was higher at impaired renal function (≤80 mL/min). Apixaban was more effective than warfarin in preventing stroke or systemic embolism and reducing mortality irrespective of renal function. These results were consistent, regardless of methods for GFR estimation. Apixaban was associated with less major bleeding events across all ranges of eGFRs. The relative risk reduction in major bleeding was greater in patients with an eGFR of ≤50 mL/min using Cockcroft-Gault {hazard ratio (HR) 0.50 [95% confidence interval (CI) 0.38-0.66], interaction P = 0.005} or CKD-EPI equations [HR 0.48 (95% CI 0.37-0.64), interaction P = 0.003]. CONCLUSION: In patients with AF, renal impairment was associated with increased risk of cardiovascular events and bleeding. When compared with warfarin, apixaban treatment reduced the rate of stroke, death, and major bleeding, regardless of renal function. Patients with impaired renal function seemed to have the greatest reduction in major bleeding with apixaban.
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Apixaban has 25% renal clearance.
“Renal clearance”
From 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS (2016) · cites this paper as [427]
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- Authors
- Hohnloser, S. H., Hijazi, Z., Thomas, L., Alexander, J. H., Amerena, J., Hanna, M., Keltai, M., Lanas, F., Lopes, R. D., Lopez-Sendon, J., Granger, C. B., & Wallentin, L.
- Affiliations
- Goethe University Frankfurt (DE)
- Uppsala University (SE)
- Duke Medical Center (US)
- Deakin University (AU)
- Bristol-Myers Squibb (United States) (US)
- Hungarian Institute of Cardiology, Semmelweis University, Budapest, Hungary
- Universidad de La Frontera (CL)
- Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA
- Hospital Universitario La Paz (ES)
- Corresponding author
- Hohnloser, Stefan H
- ORCID
- Venue
- European Heart Journal
- Publisher
- Oxford University Press (OUP)
- Published
- 2012-08-29
- Volume
- 33
- Issue
- 22
- Pages
- 2821-2830
- ISSN
- 0195-668X (ISSN-L)
- 1522-9645
- OpenAlex
- W2116559262
- Cited by
- 574
- References
- 23
- Citations by year
- 2026: 13 · 2025: 16 · 2024: 29 · 2023: 15 · 2022: 30 · 2021: 36 · 2020: 35 · 2019: 41 · 2018: 65 · 2017: 45 · 2016: 66 · 2015: 58 · 2014: 59 · 2013: 59 · 2012: 7
- FWCI
- 37.19
- Type
- journal article
- Language
- en
- Open access
- green
- figshare.com
- Licence
- Locations
- European Heart Journal (publishedVersion)
- PubMed (publishedVersion)
- Figshare (submittedVersion, cc-by)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Atrial Fibrillation Management and Outcomes
- Health Sciences › Medicine › Internal Medicine › Venous Thromboembolism Diagnosis and Management
- Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
- Keywords
- apixaban, warfarin, atrial fibrillation, renal dysfunction, glomerular filtration rate, renal function, major bleeding, stroke prevention, systemic embolism, mortality, oral anticoagulants, Cockcroft-Gault formula, CKD-EPI equation, cystatin C, ARISTOTLE trial
- MeSH terms
- Anticoagulants, Atrial Fibrillation, Female, Fibrinolytic Agents, Glomerular Filtration Rate, Hemorrhage, Humans, Male, Middle Aged, Pyrazoles, Pyridones, Risk Factors, Warfarin, Treatment Outcome, Stroke, Renal Insufficiency, Chronic
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