{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T07:00:57Z","timestamp":1769756457007,"version":"3.49.0"},"reference-count":19,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2019,8,20]],"date-time":"2019-08-20T00:00:00Z","timestamp":1566259200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,8,20]],"date-time":"2019-08-20T00:00:00Z","timestamp":1566259200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Bayer Yakuhin LTD."}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Thromb Thrombolysis"],"published-print":{"date-parts":[[2019,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The approved dose of oral anticoagulant rivaroxaban for patients with non-valvular atrial fibrillation (NVAF) in Japan is 15\u00a0mg once daily (od) in patients whose creatinine clearance is\u2009\u2265\u200950\u00a0mL\/min, but recent real-world studies have demonstrated that these patients often received less than the recommended dose due to bleeding concerns. The effect of under-dosing on safety and effectiveness outcomes remains unclear. We used 1-year follow-up data from the XAPASS, a real-world Japanese prospective, single-arm, observational study. Of the 11,308 patients, 6521 patients who completed a 1-year follow-up and had a creatinine clearance \u2265\u200950\u00a0mL\/min were included in this sub-analysis. Primary endpoints were any bleeding and a composite of stroke\/non-central nervous system systemic embolism (non-CNS SE)\/myocardial infarction (MI). Among the 6521 patients, 4185 (64.2%; mean CHADS<jats:sub>2<\/jats:sub> score: 1.8) received the 15\u00a0mg od (recommended dose), whereas 2336 (35.8%; mean CHADS<jats:sub>2<\/jats:sub> score: 2.3) received 10\u00a0mg od (under-dose). After adjusting for patient characteristics by propensity scoring and inverse probability of treatment weighting, incidence rates of major bleeding were comparable between under-dosed patients and patients who received the recommended dose (1.34 vs. 1.63 events\/100 patient-years, <jats:italic>p<\/jats:italic>\u2009=\u20090.197), although the incidence rates of stroke\/non-CNS SE\/MI were higher in under-dosed patients than in those who received the recommended dose (2.15 vs. 1.48 events\/100 patient-years, <jats:italic>p<\/jats:italic>\u2009=\u20090.009). In Japanese clinical practice, some NVAF patients receive rivaroxaban doses inconsistent with the recommendation. Considering the total clinical benefit, the recommended dose may be preferable in terms of balance of safety and effectiveness.<\/jats:p><jats:p><jats:italic>Clinicaltrials.gov<\/jats:italic> NCT01582737.<\/jats:p>","DOI":"10.1007\/s11239-019-01934-6","type":"journal-article","created":{"date-parts":[[2019,8,20]],"date-time":"2019-08-20T18:02:45Z","timestamp":1566324165000},"page":"653-660","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Outcomes associated with under-dosing of rivaroxaban for management of non-valvular atrial fibrillation in real-world Japanese clinical settings"],"prefix":"10.1007","volume":"48","clinical-trial-number":[{"clinical-trial-number":"nct01582737","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Takanori","family":"Ikeda","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoshi","family":"Ogawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takanari","family":"Kitazono","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jyoji","family":"Nakagawara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuo","family":"Minematsu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susumu","family":"Miyamoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuji","family":"Murakawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sanghun","family":"Iwashiro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoko","family":"Kidani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yutaka","family":"Okayama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshiyuki","family":"Sunaya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shoichiro","family":"Sato","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoshi","family":"Yamanaka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2019,8,20]]},"reference":[{"issue":"2","key":"1934_CR1","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1016\/j.ijcard.2008.06.029","volume":"137","author":"H Inoue","year":"2009","unstructured":"Inoue H, Fujiki A, Origasa H et al (2009) Prevalence of atrial fibrillation in the general population of Japan: an analysis based on periodic health examination. 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TI received research grants from Daiichi Sankyo, Bristol-Myers Squibb, Medtronic Japan, St. Jude Medical and Bayer Yakuhin, Ltd., and honoraria from Daiichi Sankyo, Ono, Bayer Yakuhin, Ltd., Bristol-Myers Squibb and Pfizer and TI was an advisory board member for Bristol-Myers Squibb. TK received a research grant from Bayer Yakuhin, Ltd. JN received a research grant from Nihon Medi-Physics. KM received honoraria from Bayer Yakuhin, Ltd., Otsuka, Boehringer-Ingelheim, AstraZeneca, Pfizer, Mitsubishi-Tanabe, Japan Stryker, Kowa, Nihon Medi-Physics, BMS, Sawai, Sumitomo Dainippon, Dai-ichi Sankyo, Astellas and Nippon Chemiphar, and KM was an advisory board member for CSL Behring and Medico\u2019s Hirata. SM received research grants from Takeda, CSL Behring, Meiji, MSD, Astellas, Eisai, Otsuka, Carl Zeiss Meditec, Philips Electronics Japan, Sanofi, Siemens Healthcare, Daiichi Sankyo, Mitsubishi-Tanabe, Chugai, Nihon Medi-Physics, Pfizer, Bristol-Myers Squibb, Brainlab, Mizuho and Medtronic. YM received research grants from Bayer Yakuhin, Ltd., Daiichi Sankyo and Boehringer-Ingelheim and honoraria from Bayer Yakuhin, Ltd., Daiichi Sankyo, Boehringer-Ingelheim and Bristol-Myers Squibb. SI, YK, YO, TS, SS and SY are employees of Bayer Yakuhin, Ltd.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"All procedures performed in the study were in accordance with the Good Post-marketing Study Practice standards of the Ministry of Health, Labour and Welfare in Japan.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}]}}