Thromboembolic and Hemorrhagic Outcomes in the Direct Oral Anticoagulant Trials Across the Spectrum of Kidney Function
Nita A. Limdi, T. Mark Beasley, Jielin Sun, Norman Stockbridge, Michael Pacanowski, Jeffry Florian
Abstract
Chronic kidney disease is a common comorbidity among patients taking direct‐acting oral anticoagulants (DOACs). Herein, we evaluate the influence of kidney function on stroke or systemic embolism (SEE), hemorrhage, and composite end points (stroke/SEE/hemorrhage/death and stroke/SEE/death) among patients on DOACs and warfarin. Baseline kidney function was categorized as glomerular filtration rate (GFR) ≥ 60 (reference), 45–59, and < 45mL/min/1.73 m 2 for participants in the Randomized Evaluation of Long‐Term Anticoagulant Therapy (RE‐LY) ( n = 18,049), Apixaban for Reduction in Stroke and Other Thromboembolic Events (ARISTOTLE) ( n = 18,187), and The Effective Anticoagulation with Factor Xa Next Generation in AF (ENGAGE AF) ( n = 20,798) trials. Incidence of events was compared across GFR categories. Hazard ratios for events were estimated using Cox regression using intention‐to‐treat analysis adjusting for known predictors. A large proportion of participants had GFR < 60 (25–29% had 45 ≤ GFR < 60 and 9.5–12.6% with GFR < 45). Compared with patients with GFR ≥ 60, warfarin users across the trials with GFR ≥ 45–59 and GFR < 45 had a higher incidence of hemorrhage ( P values < 0.0001) and warfarin users in the ARISTOTLE and ENGAGE trials had higher incidence of stroke/SEE ( P values ≤ 0.05). Compared with patients with GFR ≥ 60, dabigatran users with GFR ≥ 45–59 and GFR < 45 had a higher incidence of stroke/SEE ( P ≤ 0.02), hemorrhage ( P < 0.001), and both composite end points ( P < 0.0001). Compared with patients with GFR ≥ 60, apixaban and edoxaban users with GFR ≥ 45–59 and GFR < 45 had a higher incidence of hemorrhage ( P values ≤ 0.05) and composite end points ( P values ≤ 0.05). After adjustment, compared with patients with GFR ≥ 60, warfarin users with GFR < 60 in the ARISTOTLE and RE‐LY trials had a higher risk of hemorrhage ( P < 0.05), as did dabigatran ( P < 0.001) and edoxaban ( P ≤ 0.005) users, while apixaban users did not exhibit an increased risk ( P = 0.08 GFR ≥ 45–59; P = 0.71 GFR < 45). Kidney function significantly influences the safety and efficacy of oral anticoagulants.