Efficacy of Apixaban When Compared With Warfarin in Relation to Renal Function in Patients With Atrial Fibrillation: Insights From the ARISTOTLE Trial

Study Questions:

What is the effect of apixaban, a novel oral anticoagulant, on the rate of stroke, death, and bleeding among patients with atrial fibrillation in relation to renal function?


In the ARISTOTLE (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation) randomized trial, 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 7,518 patients (42%) with an estimated GFR (eGFR) of >80 ml/min, 7,587 (42%) between >50 and 80 ml/min, and 3,017 (15%) with an eGFR of ≤50 ml/min. Hazard ratios [95% confidence intervals (CI)] comparing apixaban with warfarin were derived from the Cox proportional hazards models.


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% 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).


The authors concluded that when compared with warfarin, apixaban treatment reduced the rate of stroke, death, and major bleeding, regardless of renal function.


This study reports that among patients with atrial fibrillation, the primary endpoint of stroke or systemic embolism occurred less frequently in patients assigned to apixaban than warfarin, regardless of renal function. Also, major bleeding occurred less frequently in the apixaban group. Furthermore, patients with impaired renal function seemed to have the greatest reduction in major bleeding with apixaban, when using creatinine-based estimates of GFR. In light of these data, apixaban appears to be an appealing option for these individuals, potentially leading to a substantial increase in the numbers of appropriately anticoagulated patients. Additional prospective studies are indicated comparing apixaban with other newer anticoagulants (i.e., rivaroxaban and dabigatran) in patients with renal dysfunction.

Clinical Topics: Anticoagulation Management, Novel Agents

Keywords: Stroke, Morpholines, Risk Reduction Behavior, Warfarin, Pyrazoles, Creatinine, Renal Insufficiency, Proportional Hazards Models, beta-Alanine, Benzimidazoles, Glomerular Filtration Rate, Confidence Intervals, Embolism, Pyridones, Cystatin C, Hemorrhage

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