Evaluation of edoxaban in patients with atrial fibrillation and severe renal impairment

Abstract

Purpose: Compare safety and pharmacokinetics of edoxaban (EDX) 15 mg, an oral selective FXa inhibitor, in patients with nonvalvular atrial fibrillation (NVAF) and severe renal impairment (SRI; creatinine clearance [CLCR] ≥15 to <30 mL/min) to that of EDX 60 or 30 mg in NVAF patients with normal renal function or mild renal impairment (N/MiRI; CLCR ≥50 mL/min). Methods: Patients with NVAF and SRI or N/MiRI were enrolled in a randomized, open-label study in Japan. Patients requiring hemodialysis, at high risk for bleeding, or already receiving an anticoagulant (except warfarin, rivaroxaban, or dabigatran) were excluded. SRI patients received EDX 15 mg. N/MiRI patients were randomized to either EDX 60 or 30 mg. N/MiRI patients weighing ≤60 kg or receiving concomitant treatment with quinidine or verapamil had a 50% dose reduction. EDX was administered once daily for 12 wks. Blood samples to assess plasma EDX concentrations and prothrombin time (PT) were taken at wk 2 and 8. Bleeding and adverse events (AEs) were monitored and recorded throughout the study. Results: Of 93 patients enrolled, 50 had SRI and 43 N/MiRI (21 EDX 60 mg and 22 EDX 30 mg). In the EDX 15, 60, and 30 mg groups, median CLCR was 26.3, 62.5, and 64.4 mL/min, respectively. Safety outcomes and plasma concentrations at wk 8 are provided in the Table. No major bleeding events occurred in any treatment group. No serious AE was considered related to study drug. Median PT ratios were similar between the SRI and N/MiRI 30mg groups at all time points. View this table: Bleeding, AEs, and plasma concentrations Conclusions: These results indicate that EDX 15 mg may be an appropriate therapeutic option in SRI patients with AF.