Direct oral anticoagulants versus vitamin K antagonists in patients with atrial fibrillation and stage 5 chronic kidney disease under dialysis: A systematic review and meta-analysis of randomized controlled trials

Background: In patients with atrial fibrillation (AF) and normal or slightly impaired renal function, the use of direct oral anticoagulants (DOACs) is preferable to vitamin K antagonists (VKAs). However, in patients undergoing hemodialysis, the efficacy, and safety of DOACs compared with VKAs are still unknown.

Purpose: To review current evidence about the safety and efficacy of DOACs compared to VKAs, in patients with AF and chronic kidney disease under hemodialysis.

Methods: We systematically searched PubMed, Scopus, and Cochrane databases for RCTs comparing DOACs with VKAs for anticoagulation in patients with AF on dialysis therapy. Outcomes of interest were: (1) stroke; (2) major bleeding; (3) cardiovascular mortality; and (4) all-cause mortality. Statistical analysis was performed using RevMan 5.1.7 and heterogeneity was assessed by I² statistics.

Results: Three randomized controlled trials were included, comprising a total of 383 patients. Of these, 218 received DOACs (130 received apixaban; 88 received rivaroxaban), and 165 were treated with VKAs (116 received warfarin; 49 received phenprocoumon). The incidence of stroke was significantly lower in patients treated with DOACs (4.7%) compared with those using VKAs (9.5%) (RR 0.42; 95% CI 0.18-0.97; p = 0.04; I² = 0%). However, the difference was not statistically significant in the case of ischemic stroke specifically (RR 0.42; 95% CI 0.17-1.04; p = 0.06; I² = 0%). As for the major bleeding outcome, the DOAC group (11%) had fewer events than the VKA group (13.9%) but without statistical significance (RR 0.75; 95% CI 0.45-1.28; p = 0.29; I² = 0%). There was no significant difference between groups regarding cardiovascular mortality (RR 1.23; 95% CI 0.66-2.29; p = 0.52; I² = 13%) and all-cause mortality (RR 0.98; 95% CI 0.77-1.24; p = 0.84; I² = 16%).

Conclusion: This meta-analysis suggests that in patients with AF on dialysis, the use of DOACs was associated with a significant reduction in stroke, and a numerical trend of less incidence of major bleeding compared with VKAs, but in this case with no statistical significance. Results may be limited by a small sample size or insufficient statistical power.