We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Thromboembolic and Hemorrhagic Outcomes in the Direct Oral Anticoagulant Trials Across the Spectrum of Kidney Function.
- Authors
Limdi, Nita A.; Beasley, Timothy Mark; Sun, Jielin; Stockbridge, Norman; Pacanowski, Michael; Florian, Jeffry
- 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 m2 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.
- Subjects
APIXABAN; ANTICOAGULANTS; KIDNEY physiology; THROMBOEMBOLISM; CHRONIC kidney failure; GLOMERULAR filtration rate; WARFARIN
- Publication
Clinical Pharmacology & Therapeutics, 2021, Vol 109, Issue 6, p1593
- ISSN
0009-9236
- Publication type
Article
- DOI
10.1002/cpt.2131