{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T23:11:54Z","timestamp":1780528314679,"version":"3.54.1"},"reference-count":26,"publisher":"Japanese Circulation Society","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Circ J"],"published-print":{"date-parts":[[2022,5,25]]},"DOI":"10.1253\/circj.cj-21-0617","type":"journal-article","created":{"date-parts":[[2021,11,16]],"date-time":"2021-11-16T22:07:33Z","timestamp":1637100453000},"page":"958-963","source":"Crossref","is-referenced-by-count":6,"title":["Bridging Therapy With Heparin Before Starting Rivaroxaban in Ischemic Stroke or Transient Ischemic Attack With Non-Valvular Atrial Fibrillation"],"prefix":"10.1253","volume":"86","author":[{"given":"Keisuke","family":"Tokunaga","sequence":"first","affiliation":[{"name":"Department of Cerebrovascular Medicine and Neurology, Clinical Research Institute, National Hospital Organization Kyushu Medical Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Yasaka","sequence":"additional","affiliation":[{"name":"Department of Cerebrovascular Medicine and Neurology, Clinical Research Institute, National Hospital Organization Kyushu Medical Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazunori","family":"Toyoda","sequence":"additional","affiliation":[{"name":"Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Etsuro","family":"Mori","sequence":"additional","affiliation":[{"name":"Department of Behavioral Neurology and Neuropsychiatry, United Graduate School of Child Development, Osaka University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teruyuki","family":"Hirano","sequence":"additional","affiliation":[{"name":"Department of Stroke and Cerebrovascular Medicine, Kyorin University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshimitsu","family":"Hamasaki","sequence":"additional","affiliation":[{"name":"The George Washington University Biostatistics Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Yamagami","sequence":"additional","affiliation":[{"name":"Department of Stroke Neurology, National Hospital Organization Osaka National Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takehiko","family":"Nagao","sequence":"additional","affiliation":[{"name":"Department of Neurology, Nippon Medical School, Tama-Nagayama Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinichi","family":"Yoshimura","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Hyogo College of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinichiro","family":"Uchiyama","sequence":"additional","affiliation":[{"name":"International University of Health and Welfare Director, Center for Brain and Cerebral Vessels, Sanno Medical Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuo","family":"Minematsu","sequence":"additional","affiliation":[{"name":"Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"on behalf of the RELAXED Study Investigators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"330","reference":[{"key":"1","doi-asserted-by":"crossref","unstructured":"1. Hart RG, Coull BM, Hart D. Early recurrent embolism associated with nonvalvular atrial fibrillation: A retrospective study. <i>Stroke<\/i> 1983; 14: 688\u2013693.","DOI":"10.1161\/01.STR.14.5.688"},{"key":"2","doi-asserted-by":"crossref","unstructured":"2. Kelley RE, Berger JR, Alter M, Kovacs AG. Cerebral ischemia and atrial fibrillation: Prospective study. <i>Neurology<\/i> 1984; 34: 1285\u20131291.","DOI":"10.1212\/WNL.34.10.1285"},{"key":"3","doi-asserted-by":"crossref","unstructured":"3. Douketis JD, Spyropoulos AC, Spencer FA, Mayr M, Jaffer AK, Eckman MH, et al. Perioperative management of antithrombotic therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. <i>Chest<\/i> 2012; 141: e326S\u2013e350S.","DOI":"10.1378\/chest.11-2298"},{"key":"4","doi-asserted-by":"crossref","unstructured":"4. Immediate anticoagulation of embolic stroke: A randomized trial. Cerebral Embolism Study Group. <i>Stroke<\/i> 1983; 14: 668\u2013676.","DOI":"10.1161\/01.STR.14.5.668"},{"key":"5","doi-asserted-by":"crossref","unstructured":"5. Turpie AG, Levine MN, Hirsh J, Carter CJ, Jay RM, Powers PJ, et al. Double-blind randomised trial of Org 10172 low-molecular-weight heparinoid in prevention of deep-vein thrombosis in thrombotic stroke. <i>Lancet<\/i> 1987; 1: 523\u2013526.","DOI":"10.1016\/S0140-6736(87)90173-5"},{"key":"6","doi-asserted-by":"crossref","unstructured":"6. Prins MH, Gelsema R, Sing AK, van Heerde LR, den Ottolander GJ. Prophylaxis of deep venous thrombosis with a low-molecular-weight heparin (Kabi 2165\/Fragmin) in stroke patients. <i>Haemostasis<\/i> 1989; 19: 245\u2013250.","DOI":"10.1159\/000215979"},{"key":"7","unstructured":"7. Sandset PM, Dahl T, Stiris M, Rostad B, Scheel B, Abildgaard U. A double-blind and randomized placebo-controlled trial of low molecular weight heparin once daily to prevent deep-vein thrombosis in acute ischemic stroke. <i>Semin Thromb Hemost<\/i> 1990; 16(Suppl): 25\u201333."},{"key":"8","doi-asserted-by":"crossref","unstructured":"8. Kay R, Wong KS, Yu YL, Chan YW, Tsoi TH, Ahuja AT, et al. Low-molecular-weight heparin for the treatment of acute ischemic stroke. <i>N Engl J Med<\/i> 1995; 333: 1588\u20131593.","DOI":"10.1056\/NEJM199512143332402"},{"key":"9","doi-asserted-by":"crossref","unstructured":"9. The International Stroke Trial (IST): A randomised trial of aspirin, subcutaneous heparin, both, or neither among 19435 patients with acute ischaemic stroke. International Stroke Trial Collaborative Group. <i>Lancet<\/i> 1997; 349: 1569\u20131581.","DOI":"10.1016\/S0140-6736(97)04011-7"},{"key":"10","doi-asserted-by":"crossref","unstructured":"10. Low molecular weight heparinoid, ORG 10172 (danaparoid), and outcome after acute ischemic stroke: A randomized controlled trial. The Publications Committee for the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) Investigators. <i>JAMA<\/i> 1998; 279: 1265\u20131272.","DOI":"10.1001\/jama.279.16.1265"},{"key":"11","doi-asserted-by":"crossref","unstructured":"11. Berge E, Abdelnoor M, Nakstad PH, Sandset PM. Low molecular-weight heparin versus aspirin in patients with acute ischaemic stroke and atrial fibrillation: A double-blind randomised study. HAEST Study Group. Heparin in Acute Embolic Stroke Trial. <i>Lancet<\/i> 2000; 355: 1205\u20131210.","DOI":"10.1016\/S0140-6736(00)02085-7"},{"key":"12","doi-asserted-by":"crossref","unstructured":"12. Bath PM, Iddenden R, Bath FJ. Low-molecular-weight heparins and heparinoids in acute ischemic stroke: A meta-analysis of randomized controlled trials. <i>Stroke<\/i> 2000; 31: 1770\u20131778.","DOI":"10.1161\/01.STR.31.7.1770"},{"key":"13","doi-asserted-by":"crossref","unstructured":"13. Bath PM, Lindenstrom E, Boysen G, De Deyn P, Friis P, Leys D, et al. Tinzaparin in acute ischaemic stroke (TAIST): A randomised aspirin-controlled trial. <i>Lancet<\/i> 2001; 358: 702\u2013710.","DOI":"10.1016\/S0140-6736(01)05837-8"},{"key":"14","doi-asserted-by":"crossref","unstructured":"14. Saxena R, Lewis S, Berge E, Sandercock PA, Koudstaal PJ. Risk of early death and recurrent stroke and effect of heparin in 3169 patients with acute ischemic stroke and atrial fibrillation in the International Stroke Trial. <i>Stroke<\/i> 2001; 32: 2333\u20132337.","DOI":"10.1161\/hs1001.097093"},{"key":"15","doi-asserted-by":"crossref","unstructured":"15. Camerlingo M, Salvi P, Belloni G, Gamba T, Cesana BM, Mamoli A. Intravenous heparin started within the first 3 hours after onset of symptoms as a treatment for acute nonlacunar hemispheric cerebral infarctions. <i>Stroke<\/i> 2005; 36: 2415\u20132420.","DOI":"10.1161\/01.STR.0000185730.50480.e7"},{"key":"16","doi-asserted-by":"crossref","unstructured":"16. Paciaroni M, Agnelli G, Micheli S, Caso V. Efficacy and safety of anticoagulant treatment in acute cardioembolic stroke: A meta-analysis of randomized controlled trials. <i>Stroke<\/i> 2007; 38: 423\u2013430.","DOI":"10.1161\/01.STR.0000254600.92975.1f"},{"key":"17","doi-asserted-by":"crossref","unstructured":"17. Wong KS, Chen C, Ng PW, Tsoi TH, Li HL, Fong WC, et al. Low-molecular-weight heparin compared with aspirin for the treatment of acute ischaemic stroke in Asian patients with large artery occlusive disease: A randomised study. <i>Lancet Neurol<\/i> 2007; 6: 407\u2013413.","DOI":"10.1016\/S1474-4422(07)70079-0"},{"key":"18","doi-asserted-by":"crossref","unstructured":"18. Whiteley WN, Adams HP Jr, Bath PM, Berge E, Sandset PM, Dennis M, et al. Targeted use of heparin, heparinoids, or low-molecular-weight heparin to improve outcome after acute ischaemic stroke: An individual patient data meta-analysis of randomised controlled trials. <i>Lancet Neurol<\/i> 2013; 12: 539\u2013545.","DOI":"10.1016\/S1474-4422(13)70079-6"},{"key":"19","doi-asserted-by":"crossref","unstructured":"19. Yasaka M, Minematsu K, Toyoda K, Yamagami H, Yoshimura S, Nagao T, et al. Design and Rationale of the RELAXED (Recurrent Embolism Lessened by rivaroxaban, an Anti-Xa agent, of Early Dosing for acute ischemic stroke and transient ischemic attack with atrial fibrillation) Study. <i>J Stroke Cerebrovasc Dis<\/i> 2016; 25: 1342\u20131348.","DOI":"10.1016\/j.jstrokecerebrovasdis.2016.01.035"},{"key":"20","doi-asserted-by":"crossref","unstructured":"20. Yasaka M, Minematsu K, Toyoda K, Mori E, Hirano T, Hamasaki T, et al. Rivaroxaban administration after acute ischemic stroke: The RELAXED study. <i>PLoS One<\/i> 2019; 14: e0212354.","DOI":"10.1371\/journal.pone.0212354"},{"key":"21","doi-asserted-by":"crossref","unstructured":"21. Larrue V, von Kummer RR, Muller A, Bluhmki E. Risk factors for severe hemorrhagic transformation in ischemic stroke patients treated with recombinant tissue plasminogen activator: A secondary analysis of the European-Australasian Acute Stroke Study (ECASS II). <i>Stroke<\/i> 2001; 32: 438\u2013441.","DOI":"10.1161\/01.STR.32.2.438"},{"key":"22","doi-asserted-by":"crossref","unstructured":"22. Schulman S, Kearon C, Subcommittee on Control of Anticoagulation of the Scientific Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. <i>J Thromb Haemost<\/i> 2005; 3: 692\u2013694.","DOI":"10.1111\/j.1538-7836.2005.01204.x"},{"key":"23","doi-asserted-by":"crossref","unstructured":"23. Altavilla R, Caso V, Bandini F, Agnelli G, Tsivgoulis G, Yaghi S, et al. Anticoagulation after stroke in patients with atrial fibrillation. <i>Stroke<\/i> 2019; 50: 2093\u20132100.","DOI":"10.1161\/STROKEAHA.118.022856"},{"key":"24","doi-asserted-by":"crossref","unstructured":"24. Campbell BCV. More reasons to avoid bridging anticoagulation after stroke in patients with atrial fibrillation. <i>Stroke<\/i> 2019; 50: 1950\u20131951.","DOI":"10.1161\/STROKEAHA.119.025770"},{"key":"25","doi-asserted-by":"crossref","unstructured":"25. Hori M, Matsumoto M, Tanahashi N, Momomura S, Uchiyama S, Goto S, et al. Rivaroxaban vs. warfarin in Japanese patients with atrial fibrillation: The J-ROCKET AF study. <i>Circ J<\/i> 2012; 76: 2104\u20132111.","DOI":"10.1253\/circj.CJ-12-0454"},{"key":"26","doi-asserted-by":"crossref","unstructured":"26. Tanigawa T, Kaneko M, Hashizume K, Kajikawa M, Ueda H, Tajiri M, et al. Model-based dose selection for phase III rivaroxaban study in Japanese patients with non-valvular atrial fibrillation. <i>Drug Metab Pharmacokinet<\/i> 2013; 28: 59\u201370.","DOI":"10.2133\/dmpk.DMPK-12-RG-034"}],"container-title":["Circulation Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.jstage.jst.go.jp\/article\/circj\/86\/6\/86_CJ-21-0617\/_pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,28]],"date-time":"2022-05-28T04:20:52Z","timestamp":1653711652000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jstage.jst.go.jp\/article\/circj\/86\/6\/86_CJ-21-0617\/_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,25]]},"references-count":26,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2022]]}},"URL":"https:\/\/doi.org\/10.1253\/circj.cj-21-0617","relation":{},"ISSN":["1346-9843","1347-4820"],"issn-type":[{"value":"1346-9843","type":"print"},{"value":"1347-4820","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,25]]},"article-number":"CJ-21-0617"}}