Clinical impact of kidney function in patients with atrial fibrillation receiving oral anticoagulants

Abstract Background Renal function plays a crucial role in the pharmacokinetics of oral anticoagulants, influencing both thrombotic and bleeding risks in patients with atrial fibrillation (AF). However, the association between renal function and clinical outcomes has not been comprehensively evaluated. Purpose This study aims to examine the relationship between renal function and thrombotic and bleeding events in AF patients receiving anticoagulation therapy, with a further analysis stratified by each anticoagulant. Methods We conducted a pooled analysis of three large-scale real-world registries (DIRECT-Extend registry; UMIN000050585) to evaluate the impact of renal function, assessed by creatinine clearance (Ccr), on thrombotic and bleeding events in patients with non-valvular AF receiving oral anticoagulation therapy. The primary efficacy endpoint was a composite of stroke and systemic embolism, and the primary safety endpoint was major bleeding, according to the criteria of the International Society on Thrombosis and Hemostasis. Cox proportional hazards models were used to assess the association between Ccr and clinical outcomes, incorporating restricted cubic splines to model the nonlinear relationship in the overall population and in patients receiving each anticoagulant. Results Among 7,239 eligible patients, lower Ccr was associated with an increased risk of both thrombotic and bleeding events (p0.001 for both). The impact of renal function varied by anticoagulant type. Lower Ccr was significantly associated with a higher thrombotic risk in patients receiving dabigatran (p=0.026), rivaroxaban (p=0.001), and warfarin (p=0.010), while a higher bleeding risk was observed in those receiving edoxaban (p0.001) and warfarin (p=0.023). In contrast, no significant association between Ccr and either thrombotic or bleeding risk was observed in patients receiving apixaban (efficacy endpoint, p=0.102; safety endpoint, p=0.281). Conclusions In patients with AF, impaired renal function was generally associated with an increased risk of both thrombotic and bleeding events. However, among those receiving apixaban, renal function did not significantly influence the incidence of either outcome. These results provide valuable insights for optimizing anticoagulation therapy based on individual patient characteristics.