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. Epub 2021 Apr 16.


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.

Keywords: Anticoagulation; apixaban; atrial fibrillation (AF); bleeding; chronic kidney disease (CKD); dialysis; direct oral anticoagulant (DOAC); glomerular filtration rate (GFR); network meta-analysis; pairwise meta-analysis; randomized controlled trial (RCT); renal failure; stroke; systematic review; thromboembolism; vitamin K antagonists; warfarin.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Administration, Oral
  • Anticoagulants / adverse effects
  • Atrial Fibrillation* / complications
  • Atrial Fibrillation* / drug therapy
  • Atrial Fibrillation* / epidemiology
  • Humans
  • Network Meta-Analysis
  • Renal Insufficiency, Chronic* / complications
  • Renal Insufficiency, Chronic* / drug therapy
  • Renal Insufficiency, Chronic* / epidemiology
  • Stroke*


  • Anticoagulants