Management of non-valvular atrial fibrillation (AF) in patients with advanced chronic kidney disease (CKD), including end-stage kidney disease (ESKD) requiring dialysis, remains complex due to competing risks of thrombosis and bleeding. Evidence is limited because individuals with creatinine clearance <25–30 mL/min were excluded from pivotal anticoagulation trials.

To address this gap, a meta-analysis of randomized controlled trials (RCTs) and adjusted observational studies compared direct oral anticoagulants (DOACs) with vitamin K antagonists (VKAs) in this population. The results were published in Cureus.

A systematic search of MEDLINE, Embase, and Cochrane databases identified 21 studies (4 RCTs and 17 observational cohorts), including 184,136 participants with AF and CKD stage 4–5 or dialysis. The primary efficacy outcome was stroke or systemic embolism (SE), and the primary safety outcome was major bleeding.

Pooled analyses using random-effects models showed that DOACs were associated with a lower risk of stroke or SE compared with VKAs (hazard ratio [HR] 0.72; 95% CI 0.60–0.86; p=0.0004; moderate certainty). DOACs were also associated with a lower risk of major bleeding (HR 0.74; 95% CI 0.61–0.90; p=0.0026; low to moderate certainty), although substantial heterogeneity was observed (I²=80.2%).

Agent-specific effects contributed to variability. Apixaban (HR 0.63) and rivaroxaban (HR 0.75) were associated with lower bleeding risk, whereas dabigatran was associated with higher bleeding risk (HR 1.48). Trial sequential analysis supported stroke reduction but indicated insufficient information size.