Abstract 12404: Efficacy and Safety of Apixaban Compared With Warfarin in Patients With Atrial Fibrillation and Normal Renal Function over Time: Insights From the ARISTOTLE Trial

Abstract

Introduction: It has been recently observed that one oral factor-Xa inhibitor (at the dose studied) might be associated with decreased efficacy in patients with atrial fibrillation (AF) and normal renal function. In the ARISTOTLE trial, apixaban compared to warfarin reduced stroke, mortality, and major bleeding irrespective of renal function at baseline. Our aim was to evaluate the efficacy and safety of apixaban vs. warfarin in patients with normal renal function over time. Methods: In ARISTOTLE, 16,971 patients had serial creatinine measurements available after randomization. There were a total of 397 stroke or systemic embolic events, 286 ischemic or unspecified strokes, and 712 major bleed events during median follow-up of 1.8 years. Normal renal function was predefined as an estimated glomerular filtration rate (eGFR) >80 mL/min. The relations between renal function, treatment, and outcomes were investigated by using Cox regression with renal function as a continuous time dependent covariate, fitted using restricted splines. Hazard ratios with 95% confidence intervals (CI) were analyzed based on continuous eGFR level during follow-up using both the Cockcroft-Gault and CKD-EPI equations. Results: The relative risk of stroke or systemic embolism was consistently lower in participants randomized to apixaban compared with warfarin. The patterns were similar for the ischemic or unspecified stroke outcome as well as for major bleeding (Table). Conclusions: Apixaban, relative to warfarin, demonstrated preserved efficacy and safety in AF patients with normal renal function over time.