Standard- Versus Reduced-Dose Apixaban and Vitamin K Antagonists in Patients with Atrial Fibrillation and Advanced Chronic Kidney Disease: A Systematic Review and Network Meta-Analysis

Background: The optimal apixaban dose for patients with atrial fibrillation (AF) and advanced chronic kidney disease (CKD; CrCl < 30 mL/min) remains uncertain because randomized trials largely excluded this population, and dose-specific evidence is limited. Objectives: This study aimed to compare the efficacy and safety of standard- versus reduced-dose apixaban and to evaluate each regimen against vitamin K antagonists (VKAs). Methods: We conducted a systematic review (SR) and network meta-analysis (NMA) that complied with PRISMA 2020. PubMed, Scopus, ScienceDirect, Cochrane Library, and EBSCO Open Dissertations were searched through 10 January 2026. Randomized trials and cohort studies enrolling adults with AF and CrCl < 30 mL/min were included. Primary outcomes were stroke/systemic embolism (SE) and major bleeding; secondary outcomes were any bleeding and all-cause mortality. A frequentist random-effects NMA was conducted using a consistency model. Treatment effects were estimated as hazard ratios (HRs) with 95% confidence intervals (CIs). Pairwise meta-analyses were also performed for direct comparisons. Results: Nine studies involving 65,976 patients were included. In the NMA, standard-dose apixaban did not significantly differ from reduced-dose apixaban for stroke/SE, major bleeding, or any bleeding, but was associated with lower all-cause mortality (HR 0.73, 95% CI 0.62–0.87). Compared with VKAs, both standard- and reduced-dose apixaban were associated with lower risks of stroke/SE, major bleeding, any bleeding, and all-cause mortality. Conclusions: In AF patients with advanced CKD, both standard- and reduced-dose apixaban were associated with more favorable outcomes than VKAs, although the certainty of evidence was generally low.