Background: This study reports prescribing patterns and the 1-year effectiveness and safety of edoxaban in an Asian cohort of Edoxaban Treatment in routiNe clinical prActice (ETNA)-Atrial Fibrillation (AF) patients. Methods and Results: The Global ETNA-AF program integrates prospective, observational, noninterventional regional studies, collecting data on characteristics and clinical outcomes of patients with AF receiving edoxaban for stroke prevention. Baseline characteristics, medical history, and 1-year clinical event rates were assessed in patients from South Korea, Taiwan, Hong Kong, and Thailand. Clinically relevant events assessed at 12 months included all-cause death, cardiovascular death, ischemic and hemorrhagic stroke, systemic embolic events (SEEs), bleeding, and net clinical outcome (NCO). Overall, 3,359 patients treated with edoxaban 60 or 30 mg once daily completed 1-year follow-up; 70.9% of patients received recommended dosing according to local labels. Baseline mean±standard deviation age was 71.7±9.6 years, CHA2DS2-VASc score was 3.1±1.5, and modified HAS-BLED score was 2.3±1.1. Mean age and sex were similar across countries/regions. The 1-year event rate for all-cause death was 1.8%; major bleeding, 1.3%; ischemic stroke, 1.1%; cardiovascular mortality, 0.7%; hemorrhagic stroke, 0.3%; SEEs, 0%; and NCO, 4.1%; with differences observed between countries/regions and dosing groups. Conclusions: Most Asian patients with AF were prescribed recommended edoxaban dosing in routine care settings. At 1-year follow-up, this analysis supports the effectiveness and safety of edoxaban in these patients.

Cardiology Division Department of Medicine Queen Mary Hospital The University of Hong Kong Hong Kong

Daiichi Sankyo Inc Basking Ridge NJ USA

Department of Cardiology University Heart and Vascular Center Hamburg University Medical Center Hamburg Eppendorf Hamburg Germany

Department of Medicine Bhumibol Adulyadej Hospital Bangkok Thailand

Division of Cardiology Department of Internal Medicine Chang Gung Memorial Hospital Linkou and Chang Gung University Taoyuan Taiwan

Division of Cardiology Department of Internal Medicine Korea University College of Medicine and Korea University Medical Center Seoul Republic of Korea

Division of Cardiology Department of Medicine Faculty of Medicine Srinagarind Hospital Khon Kaen University Khon Kaen Thailand

Division of Neurology Department of Medicine and Therapeutics The Faculty of Medicine The Chinese University of Hong Kong Hong Kong

German Center for Cardiovascular Sciences Partner Site Hamburg Kiel Lübeck Hamburg Germany

Institute of Cardiovascular Sciences University of Birmingham Birmingham UK

Institute of Computer Science of Academy of Sciences of the Czech Republic Prague Czech Republic

University of Pisa and Pisa University Hospital Pisa Italy

Veterans Health Service Medical Center Seoul Republic of Korea

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Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, et al.. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009; 361: 1139–1151. PubMed

Giugliano RP, Ruff CT, Braunwald E, Murphy SA, Wiviott SD, Halperin JL, et al.. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2013; 369: 2093–2104, doi:10.1056/NEJMoa1310907. PubMed

Granger CB, Alexander JH, McMurray JJV, Lopes RD, Hylek EM, Hanna M, et al.. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011; 365: 981–992. PubMed

Hindricks G, Potpara T, Dagres N, Arbelo E, Bax JJ, Blomstrom-Lundqvist C, et al.. ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): The Task Force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC. Eur Heart J 2021; 42: 373–498, doi:10.1093/eurheartj/ehaa612. PubMed

Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W, et al.. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011; 365: 883–892. PubMed

Ruff CT, Giugliano RP, Braunwald E, Hoffman EB, Deenadayalu N, Ezekowitz MD, et al.. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: A meta-analysis of randomised trials. Lancet 2014; 383: 955–962, doi:10.1016/s0140-6736(13)62343-0. PubMed

Chan YH, Kuo CT, Yeh YH, Chang SH, Wu LS, Lee HF, et al.. Thromboembolic, bleeding, and mortality risks of rivaroxaban and dabigatran in Asians with nonvalvular atrial fibrillation. J Am Coll Cardiol 2016; 68: 1389–1401, doi:10.1016/j.jacc.2016.06.062. PubMed

Cha MJ, Choi EK, Han KD, Lee SR, Lim WH, Oh S, et al.. Effectiveness and safety of non-vitamin K antagonist oral anticoagulants in Asian patients with atrial fibrillation. Stroke 2017; 48: 3040–3048, doi:10.1161/STROKEAHA.117.018773. PubMed

Shen AY, Yao JF, Brar SS, Jorgensen MB, Chen W.. Racial/ethnic differences in the risk of intracranial hemorrhage among patients with atrial fibrillation. J Am Coll Cardiol 2007; 50: 309–315, doi:10.1016/j.jacc.2007.01.098. PubMed

Pan WH, Flegal KM, Change HY, Yeh WT, Yeh CJ, Lee WC.. Body mass index and obesity-related metabolic disorders in Taiwanese and US whites and blacks: Implications for definitions of overweight and obesity for Asians. Am J Clin Nutr 2004; 79: 31–39. PubMed

Hori M, Connolly SJ, Zhu J, Liu LS, Lau CP, Pais P, et al.. Dabigatran versus warfarin: Effects on ischemic and hemorrhagic strokes and bleeding in Asians and non-Asians with atrial fibrillation. Stroke 2013; 44: 1891–1896, doi:10.1161/STROKEAHA.113.000990. PubMed

Chao TF, Chen SA, Ruff CT, Hamershock RA, Mercuri MF, Antman EM, et al.. Clinical outcomes, edoxaban concentration, and anti-factor Xa activity of Asian patients with atrial fibrillation compared with non-Asians in the ENGAGE AF-TIMI 48 trial. Eur Heart J 2019; 40: 1518–1527, doi:10.1093/eurheartj/ehy807. PubMed

Chiang CE, Okumura K, Zhang S, Chao TF, Siu CW, Wei Lim T, et al.. 2017 consensus of the Asia Pacific Heart Rhythm Society on stroke prevention in atrial fibrillation. J Arrhythm 2017; 33: 345–367, doi:10.1016/j.joa.2017.05.004. PubMed PMC

Chao TF, Joung B, Takahashi Y, Lim TW, Choi EK, Chan YH, et al.. 2021 Focused update of the 2017 consensus guidelines of the Asia Pacific Heart Rhythm Society (APHRS) on stroke prevention in atrial fibrillation. J Arrhythm 2021; 37: 1389–1426, doi:10.1002/joa3.12652. PubMed PMC

European Medicines Agency.. Lixiana: summary of product characteristics. 2015. https://www.ema.europa.eu/en/documents/product-information/lixiana-epar-product-information_en.pdf (accessed 2021).

Lee SR, Lee YS, Park JS, Cha MJ, Kim TH, Park J, et al.. Label adherence for non-vitamin K antagonist oral anticoagulants in a prospective cohort of Asian patients with atrial fibrillation. Yonsei Med J 2019; 60: 277–284, doi:10.3349/ymj.2019.60.3.277. PubMed PMC

Maura G, Blotiere PO, Bouillon K, Billionnet C, Ricordeau P, Alla F, et al.. Comparison of the short-term risk of bleeding and arterial thromboembolic events in nonvalvular atrial fibrillation patients newly treated with dabigatran or rivaroxaban versus vitamin K antagonists: A French nationwide propensity-matched cohort study. Circulation 2015; 132: 1252–1260, doi:10.1161/CIRCULATIONAHA.115.015710. PubMed PMC

De Caterina R, Agnelli G, Laeis P, Unverdorben M, Rauer H, Wang CC, et al.. The global Edoxaban Treatment in routine cliNical prActice (ETNA) noninterventional study program: Rationale and design. Clin Cardiol 2019; 42: 1147–1154, doi:10.1002/clc.23279. PubMed PMC

De Caterina R, Kim YH, Koretsune Y, Wang CC, Yamashita T, Chen C, et al.. Safety and effectiveness of edoxaban in atrial fibrillation patients in routine clinical practice: One-year follow-up from the global noninterventional ETNA-AF program. J Clin Med 2021; 10: 573, doi:10.3390/jcm10040573. PubMed PMC

Yamashita T, Koretsune Y, Ishikawa M, Shiosakai K, Kogure S.. Postmarketing surveillance on clinical use of edoxaban in patients with nonvalvular atrial fibrillation (ETNA-AF-Japan): Three-month interim analysis results. J Arrhythm 2019; 35: 121–129, doi:10.1002/joa3.12149. PubMed PMC

de Groot JR, Weiss TW, Kelly P, Monteiro P, Deharo JC, de Asmundis C, et al.. Edoxaban for stroke prevention in atrial fibrillation in routine clinical care: 1-year follow-up of the prospective observational ETNA-AF-Europe study. Eur Heart J Cardiovasc Pharmacother 2021; 7: f30–f39, doi:10.1093/ehjcvp/pvaa079. PubMed PMC

World Medical Association.. World Medical Association Declaration of Helsinki: Ethical principles for medical research involving human subjects. JAMA 2013; 310: 2191–2194. PubMed

Rodeghiero F, Tosetto A, Abshire T, Arnold DM, Coller B, James P, et al.. ISTH/SSC bleeding assessment tool: A standardized questionnaire and a proposal for a new bleeding score for inherited bleeding disorders. J Thromb Haemost 2010; 8: 2063–2065, doi:10.1111/j.1538-7836.2010.03975.x. PubMed

Yamashita T, Koretsune Y, Nagao T, Shiosakai K.. Postmarketing surveillance on the clinical use of edoxaban in patients with nonvalvular atrial fibrillation (ETNA-AF-Japan): One-year safety and effectiveness analyses. J Arrhythm 2020; 36: 395–405, doi:10.1002/joa3.12332. PubMed PMC

Chao TF, Hong KS, Lee BC, De Caterina R, Kirchhof P, Reimitz PE, et al.. Factors associated with the dosing of edoxaban for stroke prevention in patients with atrial fibrillation from South Korea and Taiwan: 1-year data from the Global ETNA-AF Program. J Chin Med Assoc 2021; 84: 485–490, doi:10.1097/jcma.0000000000000516. PubMed

Yao X, Shah ND, Sangaralingham LR, Gersh BJ, Noseworthy PA.. Non-vitamin K antagonist oral anticoagulant dosing in patients with atrial fibrillation and renal dysfunction. J Am Coll Cardiol 2017; 69: 2779–2790, doi:10.1016/j.jacc.2017.03.600. PubMed

Chan YH, Chao TF, Chen SW, Lee HF, Yeh YH, Huang YC, et al.. Off-label dosing of non-vitamin K antagonist oral anticoagulants and clinical outcomes in Asian patients with atrial fibrillation. Heart Rhythm 2020; 17: 2102–2110, doi:10.1016/j.hrthm.2020.07.022. PubMed

Steinberg BA, Shrader P, Thomas L, Ansell J, Fonarow GC, Gersh BJ, et al.. Off-label dosing of non-vitamin K antagonist oral anticoagulants and adverse outcomes: The ORBIT-AF II registry. J Am Coll Cardiol 2016; 68: 2597–2604, doi:10.1016/j.jacc.2016.09.966. PubMed