Impact of Renal Function on Outcomes With Edoxaban in Real-World Patients With Atrial Fibrillation

Background and Purpose— Edoxaban is a direct oral factor Xa inhibitor with proven efficacy and safety among patients with atrial fibrillation. Concerns have been raised about an excess of stroke among patients with creatinine clearance (CrCl) >95 mg/mL treated with edoxaban. We assessed the real-world effectiveness and safety of edoxaban in atrial fibrillation patients in relation to CrCl. Methods— In the Korean National Health Insurance Service data during the period from January to December 2016, we identified 9537 edoxaban-treated patients. Effectiveness and safety outcomes were compared between high-dose edoxaban regimen (HDER, 60 mg daily, n=2840) and a propensity score–matched warfarin group (n=2840) and between low-dose edoxaban regimen (LDER, 30 mg daily, n=3016) and matched warfarin group (n=3016). Results— The median follow-up period was 5.0 months (interquartile range, 2–7 months). The mean age was 68 years, and 63% were men in HDER group, and the mean age was 73 years, and 52% were men in LDER group. Compared with warfarin, both HDER and LDER significantly decreased the risk for ischemic stroke or systemic embolism (S/SE; HDER: adjusted hazard ratio [aHR], 0.44; 95% CI, 0.31–0.64; LDER: aHR, 0.57; 95% CI, 0.42–0.78), major bleeding (HDER: aHR, 0.40; 95% CI, 0.26–0.61; LDER: aHR, 0.61; 95% CI, 0.43–0.85), and mortality (HDER: aHR, 0.34; 95% CI, 0.22–0.53; LDER: aHR, 0.55; 95% CI, 0.41–0.73). In patients with CrCl >95 mL/min, the incidence of S/SE was higher with LDER than warfarin and comparable between HDER and warfarin group. There was lower effectiveness for the prevention of S/SE with LDER compared with warfarin at higher CrCl levels (P for interaction=0.023).Conclusions— In real-world practice, both doses of edoxaban were associated with reduced risks for S/SE, major bleeding, and mortality compared with warfarin. LDER had lower effectiveness for the prevention of S/SE compared with warfarin at higher levels of CrCl (>95 mL/min).