Safety and effectiveness of edoxaban in Japanese patients with nonvalvular atrial fibrillation: Final report of a two-year postmarketing surveillance study (ETNA-AF-Japan)

Takeshi Yamashita; Yukihiro Koretsune; Tomoko Nagao; Kazuhito Shiosakai

doi:10.1002/joa3.12520

Safety and effectiveness of edoxaban in Japanese patients with nonvalvular atrial fibrillation: Final report of a two-year postmarketing surveillance study (ETNA-AF-Japan)

J Arrhythm. 2021 Feb 24;37(2):370-383. doi: 10.1002/joa3.12520. eCollection 2021 Apr.

Authors

Takeshi Yamashita¹, Yukihiro Koretsune², Tomoko Nagao³, Kazuhito Shiosakai⁴

Affiliations

¹ The Cardiovascular Institute Tokyo Japan.
² National Hospital Organization Osaka National Hospital Osaka Japan.
³ Pharmacoepidemiology & PMS Department Daiichi Sankyo Co. Ltd Tokyo Japan.
⁴ Data Intelligence Department Daiichi Sankyo Co. Ltd Tokyo Japan.

Abstract

Background: Direct oral anticoagulants (DOACs) are the recommended first-line therapy for ischemic stroke prevention in patients with nonvalvular atrial fibrillation (NVAF). However, the safety and effectiveness of edoxaban for this indication requires monitoring over the long term in real-world settings.

Methods: ETNA-AF-Japan (trial no. UMIN000017011) was a prospective, multicenter observational study (part of postmarketing surveillance in Japan). NVAF patients due to receive edoxaban to prevent ischemic stroke were enrolled between 13 April 2015 and 30 September 2017.

Results: A total of 11 569 patients were enrolled. For the 11 111 patients (female, 40.6%) whose data comprised the safety analysis set, age, body weight, creatinine clearance (CLcr), and CHADS₂ score were 74.2 ± 10.0 years, 60.0 ± 12.7 kg, 63.9 ± 25.8 mL/min, and 2.2 ± 1.3, respectively (mean ± SD). The majority (86.3%) received edoxaban in accordance with package insert information. The mean duration of treatment was 561.9 ± 261.2 days. The annual incidence (95% confidence interval) of all bleeding events and major bleeding events was 5.60% (5.25%-5.98%) and 1.02% (0.88%-1.18%), respectively. The annual incidence of ischemic stroke (excluding transient ischemic attack, TIA) or systemic embolism was 1.08% (0.93%-1.25%). Multivariate analysis showed low body weight, low CLcr, history of gastrointestinal bleeding, anemia, and use of an antiplatelet agent to be associated with major bleeding, and history of ischemic stroke or TIA, vascular disease, and antiplatelet agent use to be associated with ischemic stroke (excluding TIA) or systemic embolism.

Conclusions: These results provide real-world evidence for the long-term good safety and effectiveness profile of edoxaban in Japanese NVAF patients under clinical practice.

Keywords: anticoagulant; atrial fibrillation; direct‐acting oral anticoagulants; edoxaban; postmarketing product surveillance.