Oral Anticoagulant Agents in Patients With Atrial Fibrillation and CKD: A Systematic Review and Pairwise Network Meta-analysis.

Abstract

OBJECTIVE\nTo evaluate the relative efficacy and safety of different oral anticoagulant agents (OACs) for patients with atrial fibrillation (AF) and chronic kidney disease (CKD).\n\n\nSTUDY DESIGN\nSystematic review and pairwise and Bayesian network meta-analysis.\n\n\nSETTING & STUDY POPULATIONS\nAdult patients with AF and CKD stages 3-5D who received OACs.\n\n\nSELECTION CRITERIA FOR STUDIES\nRandomized controlled trials (RCTs) and observational studies that reported the efficacy and safety outcomes of subgroups with a glomerular filtration rate (GFR) <60 mL/min.\n\n\nDATA EXTRACTION\nTwo reviewers independently abstracted data, assessed study quality, and rated the strength of evidence (SOE).\n\n\nANALYTICAL APPROACH\nRandom effects models using restricted maximum likelihood methods were fit for the pairwise meta-analyses as well as a network meta-analysis within a Bayesian framework.\n\n\nRESULTS\nPairwise meta-analysis including 8 RCTs and 46 observational studies showed that direct-acting oral anticoagulants (DOACs) were superior to warfarin in preventing thromboembolic events (HR, 0.86; 95% CI, 0.78-0.95) without heterogeneity (I2 = 10.5%), and in reducing the risk of bleeding events (0.81; 0.66-0.99) with substantial heterogeneity (I2 = 69.8%) in patients with AF and GFR of 15-60 mL/min. Bayesian network meta-analysis including 8 RCTs showed that dose-adjusted apixaban and a 15 mg dose of edoxaban were superior to the other OAC regimens in reducing bleeding events. Dose-adjusted apixaban was more effective than edoxaban in preventing thromboembolic events for patients with AF and GFR of 25/30-50 mL/min. In dialysis patients with AF, the use of OACs increased the risk of bleeding events by 28% (1.28; 1.03-160) without significant beneficial effects compared to not using anticoagulants.\n\n\nLIMITATIONS\nLow SOE and heterogeneity in most comparisons.\n\n\nCONCLUSIONS\nThis study suggests that DOACs are superior to warfarin for the prevention of thromboembolic events and reduction in bleeding risk in patients with AF and mild to moderate kidney disease. However, the low strength of evidence limits the conclusions that can be drawn about the preferred DOAC. Notably, the use of OACs may increase the bleeding risk without significant benefits in dialysis patients with AF.