Comparative Efficacy and Safety of Novel Oral Anticoagulants in Atrial Fibrillation with Chronic Kidney Disease: A Systematic Review, Meta-Regression, and Network Meta-Analysis

BackgroundPatients with both atrial fibrillation (AF) and chronic kidney disease (CKD) face a difficult clinical trade-off: they need protection from stroke but are at higher risk of bleeding. With more anticoagulant options now available, especially among newer oral agents, its unclear which offers the safest and most effective choice in this high-risk group. MethodsWe conducted a systematic review and network meta-analysis of randomized controlled trials involving adults with AF and CKD. We searched five major databases, focusing on three key outcomes: all-cause mortality, stroke or systemic embolism, and significant bleeding. Analyses were performed using MetaInsight in R, and risk of bias was assessed using Cochranes RoB 2.0 tool. ResultsWe included 29 trials with over 187,000 participants. Apixaban stood out across outcomes, showing the lowest risk of all-cause mortality (OR 0.45; 95% CI: 0.22-0.92) and stroke/systemic embolism (OR 0.39; 95% CI: 0.25-0.62), along with a favorable bleeding profile. Asundexian, a newer factor XIa inhibitor, showed some early promise in lowering stroke risk, but theres still not enough evidence to know how safe it really is. In contrast, warfarin and aspirin repeatedly came up short, providing less protection and carrying more risk than the newer options. These patterns remained consistent across all sensitivity and subgroup analyses. ConclusionAmong the available options, apixaban stands out as offering the most dependable mix of safety and effectiveness for patients with both AF and CKD. While newer drugs like asundexian show potential, we still need more data, particularly in those with advanced CKD, before they can be confidently recommended. In the end, treatment decisions should be tailored to each patient, taking into account their risks, kidney function, and personal needs in this complex setting.