Postmarketing surveillance on the clinical use of edoxaban in patients with nonvalvular atrial fibrillation (ETNA-AF-Japan): One-year safety and effectiveness analyses.

Takeshi Yamashita,Yukihiro Koretsune,Tomoko Nagao,Kazuhito Shiosakai

doi:10.1002/joa3.12332

Abstract

BackgroundThe safety and effectiveness of edoxaban in real‐world clinical settings have not yet been elucidated thoroughly among Japanese patients with nonvalvular atrial fibrillation (NVAF). We report the one‐year interim results of ETNA‐AF‐Japan (Edoxaban Treatment in routiNe clinical prActice in patients with nonvalvular Atrial Fibrillation: UMIN000017011), an ongoing two‐year study.MethodsETNA‐AF‐Japan is a prospective, real‐world multicenter observational study that analyzes the long‐term safety and effectiveness of edoxaban. Physicians recorded clinical characteristics, bleeding events, and clinical events of ischemic stroke and systemic embolism, among others.ResultsIn total, 11 569 patients with NVAF were enrolled. The demographic and clinical characteristics of the patients in the safety analysis set (n = 11 107) were a mean age of 74.2 ± 10.0 years; female sex, 40.6%; age ≥75 years, 52.4%; body weight ≤60 kg, 54.3%; creatinine clearance ≤50 mL/min, 31.2%; mean CHADS2 score of 2.2 ± 1.3. The mean treatment period was 311.2 days (median; 366.0 days), and ~80% of patients continued edoxaban treatment. In the safety analysis, the incidence of all bleeding events was 6.32% [95% CI: 5.87, 6.79] (n = 702), and for major bleeding, it was 1.08% [0.90, 1.29] (n = 120). In the effectiveness analysis set (n = 11 059), the incidence of ischemic stroke (excluding TIA) or systemic embolism was 1.10% [0.92, 1.32] (n = 122).ConclusionsAt one‐year follow‐up, the results showed no major concerns about the safety and effectiveness of edoxaban in Japanese patients with NVAF in a real‐world clinical setting.

Highlights

In patients with nonvalvular atrial fibrillation (NVAF), treatment with a direct oral anticoagulant (DOAC)[1-4] for ischemic stroke prevention is preferred over warfarin and especially considered for use in patients who are planning to start anticoagulant therapy as described in the “2013 Guidelines for Pharmacotherapy of Atrial Fibrillation” (JCS 2013) of the Japanese Circulation Society[5,6] and the 2018 European Heart Rhythm Association Practical Guide.[7]
A study of the long-term use of a DOAC in a large sample-size (≥10 000 patients) that analyzes the reduction in risk of ischemic stroke and systemic embolism and the occurrence of bleeding episodes would help physicians understand the most appropriate way to treat patients, elderly patients
This one-year interim analysis of 11 107 patients in the ETNA-AFJapan study provided real-world information about Japanese patients with NVAF and data on edoxaban use in high-risk patients who are commonly excluded in phase-3 studies

Summary

| INTRODUCTION

In patients with nonvalvular atrial fibrillation (NVAF), treatment with a direct oral anticoagulant (DOAC)[1-4] for ischemic stroke prevention is preferred over warfarin and especially considered for use in patients who are planning to start anticoagulant therapy as described in the “2013 Guidelines for Pharmacotherapy of Atrial Fibrillation” (JCS 2013) of the Japanese Circulation Society[5,6] and the 2018 European Heart Rhythm Association Practical Guide.[7]. We analyzed the safety and effectiveness of treatment in patients with a specific background, such as those ≥75 years old, including patients whose body weight is ≤60 kg and who have other factors. Study outcomes were recorded as AEs, including bleeding events, and clinical events such as death, stroke, systemic embolism, and myocardial infarction, the latter of which may provide information for estimating the effectiveness of edoxaban. At one-year, we had collected case report forms for 11 469 patients and excluded 362 patients (3.2%) for the following reasons: a serious protocol deviation (n = 23), nonimplementation of a safety evaluation (n = 213), consent withdrawal (n = 47), and start of edoxaban treatment with the 15 mg dose (n = 79), a dose not indicated for therapeutic use, resulting in a safety analysis set of 11 107. Patient groups whose incidence of thromboembolic events was more than double that of all patients (1.19%) were the DAPT use group (4.97%), cerebrovascular disease group (2.74%), and antiplatelet agent use group (2.56%)

| DISCUSSION

Findings

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