Oral anticoagulation in patients with atrial fibrillation and stage IV and V chronic kidney disease: a systematic review and meta-analysis
Authors: Miranda-Arboleda A F , Davila-Calle A I , Rojas-Gualdron D F , Sierra-David J G , Villegas F 
Published: October 2022

Abstract

Introduction
The association between atrial fibrillation (AF) and chronic kidney disease (CKD) is directly proportional and carries a higher risk of death, bleeding, and thromboembolism (TE). There is uncertainty on the clinical benefit of direct oral anticoagulants (DOAC) in patients with advanced stages of CKD.

Purpose
To perform a systematic review and meta-analysis of the available literature on the efficacy and safety of DOAC compared to warfarin in patients with AF and stage IV and V CKD with or without hemodialysis.

Methods
We reviewed PubMed, SCOPUS, EMBASE, LILACS, Google Scholar, Open Gray, and Clinical Trials until April 30th, 2021. A standardized search was performed independently by 2 authors. The primary efficacy endpoint was the reduction of TE (stroke or systemic embolism). The primary safety outcome was major bleeding, additional bleeding outcomes were analyzed as well. We included randomized controlled trials and observational intervention studies.

Results
We analyzed data from 80,771 patients participating in 14 studies (2 sub-analyses of randomized controlled trials and 12 observational studies). The risk of bias was low, moderate, and high in 2, 6, and 6 studies, respectively.
We did not find any difference between the use of DOAC versus warfarin to reduce the risk of TE; there was a trend but non statistically significant though (RR: 0.88 [95% CI, 0.72–1.06], I2=18.7%). Apixaban showed similar behaviour in the reduction of TE with low heterogeneity (RR: 0.86 [95% CI, 0.68–1.08], I2=0%). Conversely, dabigatran (RR: 0.73 [95% CI, 0.37–1.42], I2=17%) and rivaroxaban (RR: 1.08 [95% CI, 0.62–1.89], I2=49%) showed neutral distribution and had higher heterogeneity (Figure 1).
The risk of major bleeding was not reduced significantly by DOAC compared to warfarin (RR: 0.9 [95% CI, 0.67–1.21], I2=80.6%), apixaban showed a trend to have a lower risk of major bleeding, but it was not statistically significant (RR: 0.7 [95% CI, 0.46–1.08], I2=53.3%). Rivaroxaban expressed neutral outcome (RR: 0.94 [95% CI, 0.66–1.35], I2=68.3%), and dabigatran had a clear inclination to increase major bleeding (RR: 1.42 [95% CI, 0.99–2.04], I2=6.6%) (Figure 2).
Dabigatran significantly increased the risk of gastrointestinal bleeding in our studied population (RR: 1.49 [95% CI, 1.08–2.05]), although this conclusion was obtained from one study.

Conclusion
The use of DOAC compared to warfarin in patients with AF and stage IV and V CKD did not significantly reduce the rate of TE. There was a trend to reduce this outcome with apixaban, but it did not reach significance due to the inclusion in our study of patients in hemodialysis that represent a higher risk subgroup of patients. Major bleeding showed a similar pattern, expressing a non-statistically significant trend to be reduced in the DOAC group, especially with apixaban. Dabigatran increased the risk of bleeding by 49% in the studied population.

Funding Acknowledgement
Type of funding sources: None.