{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T14:39:26Z","timestamp":1792852766913,"version":"4.5.0"},"reference-count":37,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:sec>\n            <jats:title>BACKGROUND:<\/jats:title>\n            <jats:p>Stroke secondary to intracranial atherosclerotic disease (ICAD) is associated with high recurrence risk despite currently available secondary prevention strategies. In patients with systemic atherosclerosis, a significant reduction of stroke risk with no increase in intracranial or fatal hemorrhage was seen when rivaroxaban 2.5 mg twice daily was added to aspirin. However, there are no trials in ICAD using this combination. To facilitate the design of future ICAD trials, the CATIS-ICAD study (Combination Antithrombotic Treatment for Prevention of Recurrent Ischemic Stroke in Intracranial Atherosclerotic Disease) assessed (1) the feasibility of recruitment, (2) the safety of low-dose rivaroxaban plus aspirin compared with standard-of-care antiplatelet therapy, and (3) trends toward efficacy.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS:<\/jats:title>\n            <jats:p>This was a prospective, randomized, open-label, blinded end point pilot trial conducted in 10 Canadian centers. Eligible participants aged \u226540 years, with acute ischemic stroke or high-risk transient ischemic attack, were randomly assigned in a 1:1 ratio to receive low-dose rivaroxaban plus aspirin or aspirin alone within 7 to 100 days of their index event. The primary safety outcome was hemorrhagic stroke. The main efficacy end point was the composite of ischemic stroke or covert brain infarct on magnetic resonance imaging at the end of the study.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS:<\/jats:title>\n            <jats:p>\n              A total of 101 participants were randomized. Average enrollment was 10 participants\/site per year. Average follow-up was 20 months. Median time from index stroke to randomization was 67 days. The median age of participants was 67 years (\u00b110.94), and 29% of participants were women. There was no hemorrhagic stroke in either arm. The composite efficacy outcome was less frequent in the combination arm (15.7%) compared with the aspirin arm (24.0%), with a hazard ratio of 0.78 ([95% CI, 0.32\u20131.93];\n              <jats:italic>P<\/jats:italic>\n              =0.59) favoring the intervention.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSIONS:<\/jats:title>\n            <jats:p>A multicenter randomized trial comparing the combination of low-dose rivaroxaban and aspirin in patients with recent ischemic stroke or transient ischemic attack due to ICAD is feasible and appears safe without an increased risk of hemorrhagic stroke. A numerical trend toward efficacy for the composite primary end point of symptomatic ischemic stroke and covert infarcts was observed. These findings will inform the design of a phase III trial.<\/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: NCT04142125.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/strokeaha.124.047715","type":"journal-article","created":{"date-parts":[[2025,1,9]],"date-time":"2025-01-09T10:00:25Z","timestamp":1736416825000},"page":"380-389","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":17,"title":["Combination Antithrombotic Therapy for Reduction of Recurrent Ischemic Stroke in Intracranial Atherosclerotic Disease"],"prefix":"10.1161","volume":"56","clinical-trial-number":[{"clinical-trial-number":"nct04142125","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7646-240X","authenticated-orcid":true,"given":"Kanjana S.","family":"Perera","sequence":"first","affiliation":[{"name":"Department of Medicine (Neurology) (K.S.P., K.K.H.N.), McMaster University, Hamilton, Ontario, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6119-342X","authenticated-orcid":true,"given":"Mukul A.","family":"Sharma","sequence":"additional","affiliation":[{"name":"Population Health Research Institute (M.A.S., J.W.E., A.H.K., A. Shoamanesh, A.T., R.G.H., A.C., R.Z.), Hamilton Health Sciences, Ontario, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4126-1285","authenticated-orcid":true,"given":"John W.","family":"Eikelboom","sequence":"additional","affiliation":[{"name":"Population Health Research Institute (M.A.S., J.W.E., A.H.K., A. Shoamanesh, A.T., R.G.H., A.C., R.Z.), Hamilton Health Sciences, Ontario, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelvin Kuan Huei","family":"Ng","sequence":"additional","affiliation":[{"name":"Department of Medicine (Neurology) (K.S.P., K.K.H.N.), McMaster University, Hamilton, Ontario, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1176-0633","authenticated-orcid":true,"given":"Thalia S.","family":"Field","sequence":"additional","affiliation":[{"name":"Faculty of Medicine (T.S.F.), University of British Columbia, Vancouver, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7984-6062","authenticated-orcid":true,"given":"Brian H.","family":"Buck","sequence":"additional","affiliation":[{"name":"Division of Neurology, Department of Medicine, University of Alberta, Edmonton, Canada (B.H.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6269-1543","authenticated-orcid":true,"given":"Michael D.","family":"Hill","sequence":"additional","affiliation":[{"name":"University of Calgary and Foothills Medical Centre, Alberta, Canada (M.D.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8226-4883","authenticated-orcid":true,"given":"Grant","family":"Stotts","sequence":"additional","affiliation":[{"name":"University of Ottawa and Ottawa Hospital Research Institute, Ontario, Canada (G.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9792-1257","authenticated-orcid":true,"given":"Leanne K.","family":"Casaubon","sequence":"additional","affiliation":[{"name":"Division of Neurology, University of Toronto, Ontario, Canada (L.K.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1331-0695","authenticated-orcid":true,"given":"Jennifer","family":"Mandzia","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Western University, London, Ontario, Canada (J.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6359-0023","authenticated-orcid":true,"given":"Aristeidis H.","family":"Katsanos","sequence":"additional","affiliation":[{"name":"Population Health Research Institute (M.A.S., J.W.E., A.H.K., A. 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Bryan","family":"Young","sequence":"additional","affiliation":[{"name":"Grey Bruce Health Service, Owen Sound, Ontario, Canada (G.B.Y.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1831-5804","authenticated-orcid":true,"given":"Ramana","family":"Appireddy","sequence":"additional","affiliation":[{"name":"Division of Neurology, Department of Medicine, Queen\u2019s University, Kingston, Ontario, Canada (R.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumiti","family":"Nayar","sequence":"additional","affiliation":[{"name":"Department of Neurology (S.N., A. 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