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PLoS One. 2019 Feb 13;14(2):e0212354. doi: 10.1371/journal.pone.0212354. eCollection 2019.

Rivaroxaban administration after acute ischemic stroke: The RELAXED study.

Author information

1
Department of Cerebrovascular Medicine and Neurology, Clinical Research Institute, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan.
2
Departments of Cerebrovascular Medicine and Data Science, National Cerebral and Cardiovascular Center, Suita, Japan.
3
Department of Behavioral Neurology and Neuropsychiatry, United Graduate School of Child Development, Osaka University, Suita, Japan.
4
Department of Stroke and Cerebrovascular Medicine, Kyorin University, Tokyo, Japan.
5
Department of Neurology, Nippon Medical School, Tama-Nagayama Hospital, Tokyo, Japan.
6
Department of Neurosurgery, Hyogo College of Medicine, Hyogo, Japan.
7
International University of Health and Welfare Director, Center for Brain and Cerebral Vessels, Sanno Hospital and Sanno Medical Center, Tokyo, Japan.

Abstract

The efficacy of early anticoagulation in acute stroke with nonvalvular atrial fibrillation (NVAF) remains unclear. We performed a study to evaluate the risk of recurrent ischemic stroke (IS) and major bleeding in acute IS patients with NVAF who started rivaroxaban. This observational study evaluated patients with NVAF and acute IS/transient ischemic attack (TIA) in the middle cerebral arterial territory who started rivaroxaban within 30 days after the index IS/TIA. The primary endpoints were recurrent IS and major bleeding within 90 days after the index IS/TIA. The relationship between the endpoints and the time to start rivaroxaban was evaluated by correlation analysis using cerebral infarct volume, determined by diffusion-weighted magnetic resonance images within 48 hours of onset of the index IS/TIA. Of 1309 patients analyzed, recurrent IS occurred in 30 (2.3%) and major bleeding in 11 (0.8%) patients. Among patients with known infarct size (N = 1207), those with small (<4.0 cm3), medium (≥4.0 and <22.5 cm3), and large (≥22.5 cm3) infarcts started rivaroxaban a median of 2.9, 2.9, and 5.8 days, respectively, after the index IS/TIA. Recurrent IS was significantly less frequent when starting rivaroxaban ≤14 days versus ≥15 days after IS (2.0% versus 6.8%, P = 0.0034). Incidences of recurrent IS and major bleeding in whom rivaroxaban was started <3 days (N = 584) after IS were also low: 1.5% and 0.7%, respectively. Initiation of rivaroxaban administration in acute IS or TIA was associated with a low recurrence of IS (2.3%), and a low incidence of major bleeding events (0.8%) for 90 days after the index stroke. For the prevention of recurrent attacks in acute IS patients with NVAF, it is feasible to start the administration of rivaroxaban within 14 days of onset. Rivaroxaban started within 3 days of onset may be a feasible treatment option for patients with a small or medium-sized infarction.

Conflict of interest statement

I have read the journal's policy and have the following conflicts. Yasaka M received lecture fees from Boehringer Ingelheim, Bayer, Daiichi-Sankyo, Pfizer, BMS, Takeda, Sumitomo-Dainippon, Sanofi, Otsuka, CSL Behring, Ezai, Tanabe-Mitsubishi, Medtronic, Boston Scientific, and Sekisui Medical and research support from Sanofi, Boehringer Ingelheim, and Daiichi-Sankyo. Minematsu K received lecture fees from Bayer Healthcare, Otsuka Pharmaceutical, Boehringer-Ingelheim, AstraZeneca, Pfizer, Mitsubishi Tanabe Pharma Cooperation, Japan Stryker, Kowa, Nihon Medi-Physics Co, BMS, Sawai Pharmaceutical Co., Sumitomo Dainippon Pharma Co Ltd, Medico’s Hirata, Daiichi Sankyo, Astellas Pharma, Kyowa Hakko Kirin Pharma, Inc, Sanofi, MSD, Eisai Co., Nippon Chemiphar, and Towa Pharmaceutical Co. Toyoda K received lecture fees from Boehringer Ingelheim, Bayer, Daiichi-Sankyo, Pfizer, BMS, Takeda, Sumitomo-Dainippon, Sanofi, Otsuka, CSL Behring, Tanabe-Mitsubishi, and Kyowa-Kirin and research support from Bayer, Daiichi-Sankyo, Pfizer, Takeda, and Japan Agency for Medical Research and Development (AMED: 17ek0210091h0001, 15ek0210055h0001). Mori E received lecture fees from Johnson & Johnson, Otsuka, Novartis, Daiichi-Sankyo, Sumitomo Dainippon Pharma, Sosei, Kyowahakko-Kirin, Toshiba, Medtronic, and Nihon Medi-Physics and research support from Eisai, Daiichi-Sankyo, Novartis, Fuji Film RI, General Electric, MHWL, MEXT, and JSPS. Hirano T received lecture fees from Astellas, Bayer, Boehringer Ingelheim, BMS, CSL Behring, Daiichi-Sankyo, Eisai, Medtronic, Otsuka, Pfizer, Sumitomo-Dainippon, Sanofi, Takeda, and Tanabe-Mitsubishi and research support from Astellas, Bayer, Boehringer Ingelheim, Daiichi-Sankyo, Eisai, MSD, Otsuka, Tanabe-Mitsubishi, and JSPS KAKENHI (Grant Number 25461320, PI, 2014-2016; Grant Number 16K09731, PI, 2016-2017). Hamasaki T received lecture fees from Johnson & Johnson and research support from Teikoku Pharmaceuticals. Yamagami H received lecture fees from Boehringer Ingelheim, Bayer, Daiichi-Sankyo, Pfizer, BMS, Takeda, Sanofi, Otsuka, Tanabe-Mitsubishi, Medtronic, Striker, and Medico’s Hirata and research support from Boehringer Ingelheim and BMS. Nagao T received lecture fees from Astellas, AstraZeneca, Bayer, Bristol-Myers Squibb, Daiichi, Sankyo, Sumitomo Dainippon, Eisai, FP, Kyowa Hakko Kirin, Medtronic, Mochida, Nippon Boehringer Ingelheim, Novartis, Otsuka, Pfizer, Sanofi, Takeda, and Mitsubishi Tanabe. Yoshimura S received lecture fees from Boehringer Ingelheim, Bayer, Daiichi-Sankyo, Pfizer, BMS, Takeda, Sanofi, Otsuka, Tanabe-Mitsubishi, Medtronic, Stryker, and Medico’s Hirata and research support from BMS and Takeda. Uchiyama S received lecture fees from Boehringer Ingelheim, Bayer, Daiichi-Sankyo, Takeda, Sumitomo Dainippon, Sanofi, Otsuka, Mitsubishi Tanabe, AstraZeneca, Shionogi, and Astellas Amgen and research support from the Japan Cardiovascular Research Foundation. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

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