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

Su et al., 2021 | Am J Kidney Dis | Systematic Review

Citation

Su Xiaole, Yan Bingjuan, ... Chen Yipu. Oral Anticoagulant Agents in Patients With Atrial Fibrillation and CKD: A Systematic Review and Pairwise Network Meta-analysis. Am J Kidney Dis. 2021-Nov;78(5):678-689.e1. doi:10.1053/j.ajkd.2021.02.328

Abstract

OBJECTIVE: To evaluate the relative efficacy and safety of different oral anticoagulant agents (OACs) for patients with atrial fibrillation (AF) and chronic kidney disease (CKD). STUDY DESIGN: Systematic review and pairwise and Bayesian network meta-analysis. SETTING & STUDY POPULATIONS: Adult patients with AF and CKD stages 3-5D who received OACs. SELECTION CRITERIA FOR STUDIES: Randomized controlled trials (RCTs) and observational studies that reported the efficacy and safety outcomes of subgroups with a glomerular filtration rate (GFR)<60mL/min. DATA EXTRACTION: Two reviewers independently abstracted data, assessed study quality, and rated the strength of evidence (SOE). ANALYTICAL APPROACH: Random-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. 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 15-60mL/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 30-50mL/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. LIMITATIONS: Low SOE and heterogeneity in most comparisons. 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. REGISTRATION: Registered at PROSPERO with identification number CRD42018090896.

Key Findings

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 15-60mL/min. Bayesian network meta-analysis including 8 RCTs showed that dose-adjusted apixaban and a 15

Outcomes Measured

Requires manual extraction

Population

Field	Value
Population	atrial fibrillation
Sample Size	8
Age Range	See abstract
Condition	See abstract

MeSH Terms

Administration, Oral
Anticoagulants
Atrial Fibrillation
Humans
Renal Insufficiency, Chronic
Stroke

Evidence Classification

Level: Systematic Review
Publication Types: Journal Article, Research Support, Non-U.S. Gov't, Systematic Review, Network Meta-Analysis
Vertical: vitamin-k

Provenance

PMID: 33872690
DOI: 10.1053/j.ajkd.2021.02.328
PMCID: Not in PMC
Verified: 2026-04-09 via PubMed E-utilities API

Source extracted via PubMed E-utilities API on 2026-04-09