Renal Function and 4‐Year Outcomes in Edoxaban‐Treated Patients: A Sub‐Analysis From the ETNA ‐ AF Europe Study

ABSTRACT Background Non‐vitamin K oral anticoagulants, like edoxaban, are essential in managing atrial fibrillation (AF). The impact of renal function on edoxaban dosages in real‐world settings remains unclear. This 4‐year ETNA‐AF‐Europe study follow‐up analysis investigated how chronic kidney disease (CKD) stages affect the safety and effectiveness of usual edoxaban doses. Methods ETNA‐AF‐Europe (NCT02944019) was an observational study conducted from 2016 to 2022 across 776 centres in 10 European countries. Hazard ratios (HR) and annualized event rates were calculated for all‐cause death, cardiovascular (CV) death, stroke and bleeding events for the overall population and participants stratified by dose (30/60 mg) and CKD stages at baseline. Results Of the 13,164 participants in the full analysis set, 9114 participants with CKD (Stage 1, n = 2064; Stage 2, n = 4855; Stage 3, n = 1985; Stage 4, n = 135; missing, n = 75) received label‐recommended edoxaban doses. Compared with CKD Stage 1, higher CKD stages were associated with increased risks for stroke (Stage 3: HR [95% CI]: 1.889 [1.240–2.878], p = 0.003) and CV death (HR [95% CI]; Stage 4: 14.450 [8.270–25.247], Stage 3: 4.672 [3.312–6.969], Stage 2: 2.066 [1.394–3.062], all p < 0.001). All‐cause death followed a similar trend. After adjusting for age, sex, body weight, CHA 2 DS 2 ‐VASc and modified HAS‐BLED scores, most bleeding and effectiveness outcomes showed no nominally significant differences across CKD stages. Conclusions Edoxaban in patients with AF is effective and well tolerated across CKD stages and appropriate label dosing can offset the risk from renal impairment.