A Novel Bleeding Risk Stratification Scheme in Japanese Patients with Non-valvular Atrial Fibrillation: The J-RISK AF study

Background Oral anticoagulants (OAC) reduce the risk of ischemic stroke, but may increase the risk of major bleeding in non-valvular atrial fibrillation (NVAF) patients. Various risk scores, such as HAS-BLED, ATRIA, and ORBIT, have been proposed to assess the risk of major bleeding in NVAF patients receiving OAC. However, limited data are available on bleeding risk stratification in Japanese NVAF patients. Methods Of the 16,098 NVAF patients from the J-RISK AF study, the combined data of the five major AF registries in Japan (J-RHYTHM Registry, Fushimi AF Registry, Shinken Database, Keio interhospital Cardiovascular Studies, and Hokuriku-Plus AF Registry), we analyzed 11,539 patients receiving OAC (median age, 71 years; female, 39.6%; median CHADS2 score, 2). Multivariable Cox-hazard proportional analysis was performed to explore significant risk factors for major bleeding. Using those factors, we developed a novel bleeding risk stratification scheme and compared its predictive performance with previously reported risk scores. Results During the 2-year follow-up period, major bleeding occurred in 274 patients (1.3% per patient-year). On multivariable analysis, advanced age, uncontrolled hypertension, history of bleeding, anemia, thrombocytopenia, and concomitant antiplatelet agents were significantly associated with higher incidence of major bleeding. We developed a novel risk stratification system, J-RISK bleeding score, that had good predictive performance (C-statistics 0.67) for major bleeding. The predictive performance of our score was better than previous scores. Conclusion Our findings suggest that our novel risk stratification system, the J-RISK bleeding score, is more useful than previous score systems for Japanese NVAF patients receiving OAC. ### Competing Interest Statement Dr Akao received research funding from Bayer, and Daiichi-Sankyo, and Speakers? Bureau/Honorarium from Pfizer, Bristol-Myers Squibb, Boehringer Ingelheim, Bayer and Daiichi Sankyo.; Dr. Tomita received research funding from Boehringer Ingelheim, Bayer, Daiichi-Sankyo, and Pfizer, and Speakers? Bureau/Honorarium from Boehringer Ingelheim, Bayer, Daiichi-Sankyo, and Bristol-Myers Squibb; Dr. Kodani received remuneration from Daiichi-Sankyo; Dr. Suzuki received Speakers? Bureau/Honorarium from Daiichi-Sankyo and Bristol-Myers Squibb; Dr. Hayashi received Speakers? Bureau/Honorarium from Bayer, Daiichi-Sankyo, and Bristol-Myers Squibb; Dr. Sawano received lecture fees from Boehringer Ingelheim, Bristol-Myers Squibb, Astellas Pharma, Sanofi, and research funding from Takeda Pharmaceutical; Dr. Goya received Speakers? Bureau/Honorarium from Daiichi-Sankyo, Abbott, and Japan Life Line; Dr. Yamashita received research funding from Daiichi-Sankyo and Bristol-Myers Squibb, and Speakers? Bureau/Honorarium from Daiichi-Sankyo, Bristol-Myers Squibb, Bayer, Ono Pharmaceutical, Boehringer Ingelheim, Novartis, Otsuka Pharmaceutical and Toa Eiyo; Dr. Isobe received research funding from Medtronic, Abbott, Boston Scientific, BIOTRONIK, Japan Life Line, Terumo, NIPRO, DVx, Active Medical, TORAY INDUSTRIES, KANEKA MEDIX, Johnson & Johnson, and Boehringer Ingelheim; Dr. Toyoda received Speakers? Bureau/Honorarium from Daiichi-Sankyo, Otsuka Pharmaceutical, Bayer, Bristol-Myers-Squibb, and Novartis; Dr. Okamura received Speakers? Bureau/Honorarium from Bayer and Daiichi-Sankyo. The rest of the authors have no relevant disclosures. ### Funding Statement This research is supported by the Practical Research Project for Life-Style related Diseases including Cardiovascular Diseases and Diabetes Mellitus from Japan Agency for Medical Research and Development, AMED (19ek0210082h0003). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Not Applicable The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study was approved and an exemption of informed consent was granted by the ethics committee of the Hirosaki University Graduate School of Medicine, Hirosaki, Japan, because the integrated data used did not include personally identifiable information. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Not Applicable I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Not Applicable I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Not Applicable The data underlying this article will be shared on reasonable request to the corresponding author.