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

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

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Introduction

Atrial fibrillation (AF) is the most common cardiac arrhythmia and it is frequently encountered in chronic kidney disease (CKD) patients. CKD patients are already at high risk for cardiovascular (CV) complications and the addition of AF further aggravates the prognosis. Among patients with CKD, there is a progressively increased risk of  ischemic stroke, Atrial Fibrillation  and hemorrhage as renal function declines, complicating the decision to initiate anticoagulation.

Whether to initiate oral anticoagulant therapy in advanced chronic kidney disease patients with atrial fibrillation remains debatable. Although randomized trial data are lacking, observational studies yield controversial results. This study evaluates the relative efficacy and safety of different oral anticoagulant agents (OACs) for patients with atrial fibrillation and chronic kidney disease.

Study Design

A systematic review and pairwise and Bayesian network meta-analysis was carried out for this study.  The study population included adult patients with AF and CKD stages 3-5D who received OACs. Randomized controlled trials (RCTs) and observational studies that reported the efficacy and safety outcomes of subgroups with a glomerular filtration rate (GFR) <60 mL/min were included in the study. Within a Bayesian framework, random-effects models with constrained maximum-likelihood approaches were fit for paired meta-analyses and a network meta-analysis.

Results

Pairwise meta-analysis including 8 RCTs and 46 observational studies showed that direct OACs (DOACs) were superior to warfarin in preventing thromboembolic events (hazard ratio [HR], 0.86 [95% CI, 0.78-0.95]), without heterogeneity (I2 = 10.5%), and in reducing the risk of bleeding events (HR, 0.81 [95% CI, 0.66-0.99]), with substantial heterogeneity (I2 = 69.8%), in patients with AF and a 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 in the range of 25-50 or 30-50 mL/min.  In dialysis recipients with AF, the use of OACs increased the risk of bleeding events by 28% (HR, 1.28 [95% CI, 1.03-1.60]) without significant beneficial effects versus not using anticoagulants.

Conclusions

This 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 SOE limits the conclusions that can be drawn about the preferred DOAC. Notably, the use of OACs may increase bleeding risk without significant benefits in dialysis recipients with AF.

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