{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T03:41:26Z","timestamp":1747194086828,"version":"3.40.5"},"reference-count":24,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2020,7]]},"abstract":"<jats:sec>\n            <jats:title>Background and Purpose:<\/jats:title>\n            <jats:p>Risks, sites, and predictors of major bleeding during antithrombotic therapies have not been well defined for patients with recent embolic stroke of undetermined source.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>Exploratory analysis of major bleeds defined by International Society of Thrombosis and Hemostasis criteria occurring among 7213 participants in international NAVIGATE (New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial) embolic stroke of undetermined source randomized trial comparing rivaroxaban 15 mg daily with aspirin 100 mg daily.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>\n              During a median follow-up of 11 months, 85 major bleeds occurred. The most frequent site was gastrointestinal (38%), followed by intracranial (29%). Assignment to rivaroxaban (hazard ratio [HR], 2.7 [95% CI, 1.7\u20134.3]), East Asia region (HR, 2.5 [95% CI, 1.6\u20133.9]), systolic blood pressure \u2265160 mm Hg (HR, 2.2 [95% CI, 1.2\u20133.8]), and reduced estimated glomerular filtration rate (HR, 1.2 per 10 mL\/min per 1.73 m\n              <jats:sup>2<\/jats:sup>\n              decrease, [95% CI, 1.0\u20131.3]) were independently associated with presence of major bleeds. Five (6%) were fatal. Among 15 patients with intracerebral hemorrhage, 2 (13%) were fatal. There was no evidence of an early high-risk period following initiation of rivaroxaban. The annualized rate of intracerebral hemorrhage was 6-fold higher among East Asian participants (0.67%) versus all other regions (0.11%; HR, 6.3 [95% CI, 2.2\u201318.0]). Distribution of bleeding sites was similar for rivaroxaban and aspirin.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>Among embolic stroke of undetermined source patients participating in an international randomized trial, independent predictors of major bleeding were assignment to rivaroxaban, East Asia region, increased systolic blood pressure, and impaired renal function. East Asia as a region was strongly associated with risk of intracerebral hemorrhage. Estimated glomerular filtration rate should be a consideration for stratifying bleeding risk.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Registration:<\/jats:title>\n            <jats:p>\n              URL:\n              <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\">https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n              . Unique identifier: NCT02313909.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/strokeaha.119.027995","type":"journal-article","created":{"date-parts":[[2020,6,10]],"date-time":"2020-06-10T09:00:21Z","timestamp":1591779621000},"page":"2139-2147","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":6,"title":["Frequency and Predictors of Major Bleeding in Patients With Embolic Strokes of Undetermined Source"],"prefix":"10.1161","volume":"51","clinical-trial-number":[{"clinical-trial-number":"nct02313909","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7458-5166","authenticated-orcid":false,"given":"Robert","family":"Mikul\u00edk","sequence":"first","affiliation":[{"name":"International Clinical Research Center and Neurology Department, St. Anne\u2019s University Hospital and Masaryk University Brno, Czech Republic (R.M.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jens","family":"Eckstein","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University Hospital Basel, Switzerland (J.E.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lesly A.","family":"Pearce","sequence":"additional","affiliation":[{"name":"Biostatistics Consultant, Minot, ND (L.A.P.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hardi","family":"Mundl","sequence":"additional","affiliation":[{"name":"Bayer AG, Wuppertal, Germany (H.M.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salvatore","family":"Rudilosso","sequence":"additional","affiliation":[{"name":"Comprehensive Stroke Center, Department of Neuroscience (S.R.), Hospital Clinic, Barcelona, Spain."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Veron\u00edca V.","family":"Olavarr\u00eda","sequence":"additional","affiliation":[{"name":"Department of Neurology and Psychiatry, Faculty of Medicine, Universidad del Desarrollo, Cl\u00ednica Alemana de Santiago, Santiago, Chile (V.V.O.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashkan","family":"Shoamanesh","sequence":"additional","affiliation":[{"name":"McMaster University\/Population Health Research Institute, Hamilton Health Sciences, ON, Canada (A.S., S.J.C., R.G.H.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u00c1ngel","family":"Chamorro","sequence":"additional","affiliation":[{"name":"Comprehensive Stroke Center, Department of Neuroscience (A.C.), Hospital Clinic, Barcelona, Spain."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joan","family":"Mart\u00ed-F\u00e0bregas","sequence":"additional","affiliation":[{"name":"Hospital de La Santa Creu Isant Pau, Barcelona, Spain (J.M.-F.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roland","family":"Veltkamp","sequence":"additional","affiliation":[{"name":"Imperial College London, United Kingdom (R.V.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u015eerefnur","family":"\u00d6zt\u00fcrk","sequence":"additional","affiliation":[{"name":"Department of Neurology, Selcuk University Faculty of Medicine, Turkey (S.O.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Turgut","family":"Tatlisumak","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Sweden (T.T.)."},{"name":"Department of Neurology, Sahlgrenska University Hospital, Gothenburg, Sweden (T.T.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W. 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