Abstract 16326: Safety and Efficacy of Novel Oral Anticoagulants in Subjects With Atrial Fibrillation in Relation to Renal Function: Meta-analysis of Randomized Clinical Trials

Abstract

Introduction: The efficacy and safety of novel oral anticoagulants (NOACs) has not been assessed in subjects with renal impairment. Methods: We performed a meta-analysis of RCTs comparing NOACs with warfarin in patients with atrial fibrillation (AF), in relation to renal function estimated by glomerular filtration rate (GFR): normal (GFR>80 ml/min/1.73m2), mild (50-80 mL/min/1.73m2), and moderate (<50 mL/min/1.73m2) impairment. MEDLINE, Embase, Web of Science and the Cochrane Library were searched to identify articles published up to the third week of January 2015. Data were supplemented with FDA data. Data on stroke or systemic embolism (S/SE) and major bleeding according to renal function were collected and extracted. We estimated the pooled relative risk (RR) of S/SE and major bleeding, for NOACs compared to warfarin. Results: We retrieved four randomized clinical trials (each randomizing dabigatran, rivaroxaban, apixaban, or endoxaban versus warfarin) enrolling a total of 58338 subjects, 29123 randomized to NOACs and 29123 randomized to warfarin; 21132 had normal renal function, 13126 had mild and 11027 had moderate renal impairment. In subjects with moderate renal impairment, compared to warfarin, NOACs reduced the risk of S/SE (RR 0.8; 95% CI 0.68-0.94) and major bleeding (RR 0.80; 95% CI 0.71-0.91). In subjects with mild renal impairment NOACs were associated with a reduced risk of S/SE (RR 0.75; 95% CI 0.66-0.85) and major bleeding (RR 0.87; 95% CI 0.79-0.95). In subjects with normal renal function no difference in the risk of S/SE was observed, while the risk of major bleeding was slightly less for subjects taking NOACs (RR 0.87; 95% CI 0.76-0.99). The test for interaction among groups of renal function was borderline significant for S/SE, but not for major bleeding. Conclusions: The use of NOACs was associated with a reduced risk of S/SE in subjects with mild or moderate renal impairment; while the risk of bleeding was reduced by NOACs compared to warfarin.