Direct Oral Anticoagulants Versus Warfarin in Atrial Fibrillation With Advanced Chronic Kidney Disease: A Systematic Review and Meta-Analysis.

Patients with non-valvular atrial fibrillation (AF) and advanced chronic kidney disease (CKD), including those with end-stage kidney disease (ESKD) on dialysis, present a unique therapeutic challenge. This population is at an elevated risk for both thromboembolic events and severe bleeding complications. Because patients with creatinine clearance <25-30 mL/min were excluded from pivotal trials, the comparative safety and efficacy of direct oral anticoagulants (DOACs) versus traditional vitamin K antagonists (VKAs) in this cohort remain debated. A search of MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials was performed from inception to the present to identify randomized controlled trials (RCTs) and adjusted observational studies comparing DOACs to VKAs in patients with AF and advanced CKD (stages 4-5 or dialysis). The primary outcomes were stroke or systemic embolism (SE) (efficacy) and major bleeding (safety). Hazard ratios (HRs) and 95% confidence intervals (CIs) were pooled using a random-effects (DerSimonian-Laird) model. Meta-regression, trial sequential analysis (TSA), and GRADE certainty assessments were applied. The final analysis included 21 studies (four RCTs, 17 observational cohorts) encompassing 184,136 participants. Compared to VKAs, DOACs were associated with a statistically significant 28% reduction in the risk of stroke or SE (heart rate (HR), 0.72; 95% confidence interval (CI), 0.60-0.86;