BACKGROUND: Randomized clinical trials demonstrated similar efficacy and improved safety of direct oral anticoagulants versus warfarin in patients with atrial fibrillation (AF). Long-term data in routine clinical practice are needed. HYPOTHESIS: Patients with AF receiving edoxaban at baseline continue to have low annualized effectiveness and safety event rates in the second year of follow-up, with regional variations observed. METHODS: The Global ETNA-AF program is a prospective, noninterventional study of patients with AF receiving edoxaban. Patient characteristics and annualized clinical event rates were assessed overall and by region across the 2-year follow-up. Annualized event rates of bleeding and thromboembolic events were assessed within the first year and conditionally in patients who were event-free up to 12 months in the second year. RESULTS: This analysis comprised 26 805 patients from Europe (n = 13 164), Japan (n = 10 342), and non-Japanese Asian regions (n = 3299). Patients from Europe had the highest burden of comorbidities. The annualized event rates for major bleeding, any stroke, all-cause death, and cardiovascular death varied by region. The global annualized event rates in the first and second year were 1.31%/year and 0.86%/year for major bleeding, 1.06%/year and 0.65%/year for any stroke, 0.84%/year and 0.73%/year for cardiovascular death, and 3.05%/year and 3.18%/year for all-cause death. CONCLUSION: Annualized event rates for any stroke and major bleeding remained low through 2-year follow-up for patients with AF receiving edoxaban at baseline. Differences in annualized event rates for all-cause and cardiovascular mortality between Europe, Japan, and non-Japanese Asian regions may reflect variations in baseline characteristics. TRIAL REGISTRATION: Europe, NCT02944019; Japan, UMIN000017011; Korea/Taiwan, NCT02951039; Hong Kong, NCT03247582; and Thailand, NCT03247569.

Center for Cardiovascular Research University of Birmingham and SWBH and UHB NHS Trusts Birmingham UK

Chair of Cardiology University of Pisa and Cardiology Division Pisa University Hospital Pisa Italy

Daiichi Sankyo Inc Basking Ridge USA

Department of Cardiology Chang Gung Memorial Hospital Chang Gung University Taoyuan Taiwan

Department of Cardiology University Heart and Vascular Center Hamburg Hamburg Germany

Department of Cardiovascular Medicine Cardiovascular Institute Tokyo Japan

Department of Internal Medicine Seoul National University College of Medicine and Seoul National University Hospital Seoul Republic of Korea

Department of Surgical Division of Cardiology Medical and Molecular Pathology and Critical Care Medicine University of Pisa Pisa Italy

Fondazione Villa Serena per la Ricerca Città Sant'Angelo Italy

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

Institute for Pharmacology and Preventive Medicine Cloppenburg Germany

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

Medical Faculty Charles University Pilsen Czech Republic

National Hospital Organization Osaka National Hospital Osaka Japan

Zobrazit více v PubMed

Furie K. L., Goldstein L. B., Albers G. W., et al., “Oral Antithrombotic Agents for the Prevention of Stroke in Nonvalvular Atrial Fibrillation: A Science Advisory for Healthcare Professionals From the American Heart Association/American Stroke Association,” Stroke 43, no. 12 (2012): 3442–3453. PubMed

Giugliano R. P., Ruff C. T., Braunwald E., et al., “Edoxaban Versus Warfarin in Patients With Atrial Fibrillation,” New England Journal of Medicine 369, no. 22 (2013): 2093–2104. PubMed

Ruff C. T., Giugliano R. P., Braunwald E., 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 383, no. 9921 (2014): 955–962. PubMed

Hindricks G., Potpara T., Dagres N., et al., “2020 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,” European Heart Journal 42, no. 5 (2021): 373–498. PubMed

Otto C. M., Nishimura R. A., Bonow R. O., et al., “2020 ACC/AHA Guideline for the Management of Patients With Valvular Heart Disease: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines,” Circulation 143, no. 5 (2021): e72–e227. PubMed

Chao T. F., Joung B., Takahashi Y., et al., “2021 Focused Update Consensus Guidelines of the Asia Pacific Heart Rhythm Society on Stroke Prevention in Atrial Fibrillation: Executive Summary,” Thrombosis and Haemostasis 122, no. 1 (2022): 020–047. PubMed PMC

De Caterina R., Agnelli G., Laeis P., et al., “The Global Edoxaban Treatment in Routine Clinical Practice (ETNA) Noninterventional Study Program: Rationale and Design,” Clinical Cardiology 42, no. 12 (2019): 1147–1154. PubMed PMC

De Caterina R., Kim Y. H., Koretsune Y., 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,” Journal of Clinical Medicine 10, no. 4 (2021): 573. PubMed PMC

Singh K. and Prabhakaran D., “Disparities in Representation of Asian Participants and Investigators in Cardiometabolic Trials,” JACC: Asia 3, no. 5 (2023): 736–738. PubMed PMC

Azzopardi R., Nicholls S. J., Nerlekar N., et al., “Asia‐Pacific Investigators and Asian Enrollment in Cardiometabolic Trials,” JACC: Asia 3, no. 5 (2023): 724–735. PubMed PMC

Qureshi N. Q., Mufarrih S. H., Bloomfield G. S., et al., “Disparities in Cardiovascular Research Output and Disease Outcomes Among High‐, Middle‐ and Low‐Income Countries—An Analysis of Global Cardiovascular Publications Over the Last Decade (2008–2017),” Global Heart 16, no. 1 (2021): 4. PubMed PMC

Huisman M. V., Rothman K. J., Paquette M., et al., “Two‐Year Follow‐Up of Patients Treated With Dabigatran for Stroke Prevention in Atrial Fibrillation: Global Registry on Long‐Term Antithrombotic Treatment in Patients With Atrial Fibrillation (GLORIA‐AF) Registry,” American Heart Journal 198 (2018): 55–63. PubMed

Camm A. J., Amarenco P., Haas S., et al., “XANTUS: A Real‐World, Prospective, Observational Study of Patients Treated With Rivaroxaban for Stroke Prevention in Atrial Fibrillation,” European Heart Journal 37, no. 14 (2016): 1145–1153. PubMed PMC

Martínez C. A. A., Lanas F., Radaideh G., et al., “XANTUS‐EL: A Real‐World, Prospective, Observational Study of Patients Treated With Rivaroxaban for Stroke Prevention in Atrial Fibrillation in Eastern Europe, Middle East, Africa and Latin America,” Egyptian Heart Journal 70, no. 4 (2018): 307–313. PubMed PMC

Li X., Deitelzweig S., Keshishian A., et al., “Effectiveness and Safety of Apixaban Versus Warfarin in Non‐Valvular Atrial Fibrillation Patients in “Real‐World” Clinical Practice. A Propensity‐Matched Analysis of 76,940 Patients,” Thrombosis and Haemostasis 117, no. 6 (2017): 1072–1082. PubMed PMC

Rodeghiero F., Tosetto A., Abshire T., et al., “ISTH/SSC Bleeding Assessment Tool: A Standardized Questionnaire and a Proposal for a New Bleeding Score for Inherited Bleeding Disorders,” Journal of Thrombosis and Haemostasis 8, no. 9 (2010): 2063–2065. PubMed

Hamatani Y., Ogawa H., Uozumi R., et al., “Low Body Weight Is Associated With the Incidence of Stroke in Atrial Fibrillation Patients—Insight From the Fushimi AF Registry,” Circulation Journal 79, no. 5 (2015): 1009–1017. PubMed

Khan S. S., Ning H., Wilkins J. T., et al., “Association of Body Mass Index With Lifetime Risk of Cardiovascular Disease and Compression of Morbidity,” JAMA Cardiology 3, no. 4 (2018): 280–287. PubMed PMC

Must A., J. Spadano, E. H. Coakley, et al., “The Disease Burden Associated With Overweight and Obesity,” Journal of the American Medical Association 282, no. 16 (1999): 1523–1529. PubMed

Abdullah A., Peeters A., de Courten M., and Stoelwinder J., “The Magnitude of Association Between Overweight and Obesity and the Risk of Diabetes: A Meta‐Analysis of Prospective Cohort Studies,” Diabetes Research and Clinical Practice 89, no. 3 (2010): 309–319. PubMed

Kivimäki M., Kuosma E., Ferrie J. E., et al., “Overweight, Obesity, and Risk of Cardiometabolic Multimorbidity: Pooled Analysis of Individual‐Level Data for 120 813 Adults From 16 Cohort Studies From the USA and Europe,” Lancet Public Health 2, no. 6 (2017): e277–e285. PubMed PMC

Krittayaphong R., Winijkul A., Wongtheptien W., et al., “History of Major Bleeding Predicts Risk of Clinical Outcome of Patients With Atrial Fibrillation: Results From the COOL‐AF Registry,” Journal of geriatric cardiology: JGC 17, no. 4 (2020): 184–192. PubMed PMC

Lip G. Y. H., Clementy N., Pericart L., Banerjee A., and Fauchier L., “Stroke and Major Bleeding Risk in Elderly Patients Aged ≥75 Years With Atrial Fibrillation: The Loire Valley Atrial Fibrillation Project,” Stroke 46, no. 1 (2015): 143–150. PubMed

Krittayaphong R., Chichareon P., Komoltri C., Kornbongkotmas S., Yindeengam A., and Lip G. Y. H., “Low Body Weight Increases the Risk of Ischemic Stroke and Major Bleeding in Atrial Fibrillation: The COOL‐AF Registry,” Journal of Clinical Medicine 9, no. 9 (2020): 2713. PubMed PMC

Gomes T., Mamdani M. M., Holbrook A. M., Paterson J. M., Hellings C., and Juurlink D. N., “Rates of Hemorrhage During Warfarin Therapy for Atrial Fibrillation,” Canadian Medical Association Journal 185, no. 2 (2013): E121–E127. PubMed PMC

Shimada Y. J., Yamashita T., Koretsune Y., et al., “Effects of Regional Differences in Asia on Efficacy and Safety of Edoxaban Compared With Warfarin—Insights From the ENGAGE AF‐TIMI 48 Trial,” Circulation Journal 79, no. 12 (2015): 2560–2567. PubMed

Bassand J. P., Accetta G., Camm A. J., et al., “Two‐Year Outcomes of Patients With Newly Diagnosed Atrial Fibrillation: Results From GARFIELD‐AF,” European Heart Journal 37, no. 38 (2016): 2882–2889. PubMed PMC

Zobrazit více v PubMed

ClinicalTrials.gov
NCT03247582, NCT03247569, NCT02944019, NCT02951039