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Chronic kidney disease (CKD) and atrial fibrillation (AF) are common medical conditions that often occur together, creating complex challenges for patient management. Traditional anticoagulants like warfarin require close monitoring and have numerous interactions. Direct oral anticoagulants (DOACs) have emerged as alternatives, but their use in CKD patients is debated. Understanding the potential benefits and risks of novel anticoagulation therapies in CKD patients with AF is essential for optimizing their management and reducing the burden of stroke and thromboembolic events in this vulnerable population. The coexistence of CKD and AF requires a careful evaluation of anticoagulation strategies. There are many conflicting results based on cohort analysis and prospective registries. Consequently, the choice of a specific anticoagulant should be based on solid evidence obtained from randomized clinical trials, which shows the relevance of this research.
We conducted electronic searches to identify relevant studies in PubMed, Embase, and the Cochrane Library for this systematic review. Out of 386 studies, 9 Randomized controlled trials published up to September 2023, which met the inclusion criteria of AF+CKD, were included. Review Manager (Revman) 5.4, a variance-weighted random effects model, was used to estimate event rates and odds ratio. A composite of thromboembolic stroke and systemic embolism defined our primary efficacy. All cause of mortality defined our secondary efficacy, and our primary safety was defined by a composite of major or clinically relevant non-major bleeds.
A pooled analysis of 9 RCTs showed that the primary endpoint for efficacy occurred in 1606 out of 50430 patients. 797 events out of 27713 patients occurred in the DOAC group, and 809 out of 22717 patients occurred in the warfarin group (OR=0.80;95%CI 0.72,0.89; P<0.0001) (Fig 1). The primary safety endpoint (major and clinically relevant non-major bleeding) happened more frequently than stroke and systemic embolism. Total major and clinically relevant non-major events occurred in 2671 out of 46214 patients. 1227 out of 25633 in the DOAC group and 1444 out of 20581 in the warfarin group (OR=0.63;95%CI 0.49,0.82; P=0.0006) (Fig 2). The pooled estimate event for all-cause mortality was 2711 out of 25810. 1493 out of 15230 occurred in the DOAC group vs 1218 out of 10508 in the warfarin group (OR=0.91;95%CI 0.84, 0.99; P=0.02) (Fig 3). Comparing DOAC with Warfarin showed a decreased risk of stroke or systemic embolism and a significantly reduced risk of bleeding and death.
From the pooled analysis of the RCTs, we can conclude that DOAC shows better efficacy and safety of novel anticoagulants for preventing thromboembolic events in patients with chronic kidney disease and Atrial fibrillation. The Beneficial effect of DOAC over warfarin is consistent with all stages of CKD.