Comparison of the Safety and Efficacy of Direct Oral Anticoagulants and Warfarin in Atrial Fibrillation or Venous Thromboembolism in Patients with Renal Impairment: Systematic Review, Meta-Analysis and Network Meta-Analysis.

Abstract

Due to the high risk of ischemic and arterial or venous bleeding events in atrial fibrillation (AF) or venous thromboembolism (VTE) patients with renal impairment (RI), selection of appropriate anticoagulant regimen is important. Therefore, we systematically reviewed and compared the safety and effects of oral anticoagulants in AF and VTE patients with RI. Eligible articles were identified through a literature search in PubMed, Embase, ClinicalTrials.gov, and the Cochrane Library for studies published between January 2008 and November 2020. Network meta-analysis was conducted with STATA 14.0 to analyze the effects and safety of each drug with regard to different levels of renal function. 15 studies including 82,931 patients (76,957 with AF and 5974 with VTE) were analyzed. Compared with those of warfarin, the risk ratios of effect and safety outcomes of apixaban were 0.70 (95% confidence interval [CI] 0.60-0.82) and 0.56 (95% CI 0.42-0.76) in AF patients and 0.33 (95% CI 0.19-0.59) and 0.95 (95% CI 0.68-1.34) in VTE patients. Apixaban had the first or second highest probability of being ranked first with respect to surface under the cumulative ranking curve (SUCRA) scores in the prevention of major bleeding events, while in the prevention of ischemic events, rivaroxaban showed a higher SUCRA score (0.78-0.92) in mild RI patients and dabigatran showed a higher SUCRA value (0.90-0.99) in moderate RI patients. In the systematic review and meta-analysis, for AF or VTE patients with RI, direct oral anticoagulants performed comparably to or better than warfarin with regard to safety and effects. The network meta-analysis indicated that for patients with mild RI, apixaban might be safer for patients with a lower risk of ischemic events, while rivaroxaban might be suitable for patients with a lower risk of bleeding events. For patients with moderate RI, apixaban could reduce the risk of ischemic events without increasing the risk of bleeding events. For AF patients with severe RI, apixaban, rivaroxaban, and warfarin showed a similar effect. These results might provide suggestions for clinical arterial and venous thrombosis prevention.