{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T10:12:56Z","timestamp":1788430376830,"version":"build-2803163510"},"reference-count":16,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:sec>\n            <jats:title>BACKGROUND:<\/jats:title>\n            <jats:p>Oral anticoagulants are superior to antiplatelet agents for preventing cardioembolic stroke but concerns about increased risk of intracranial hemorrhage limit their use. Although rivaroxaban demonstrably increases intracranial bleeding risk compared with aspirin, the comparative risk of intracranial hemorrhage with apixaban versus aspirin remains uncertain. We aimed to clarify this risk through a meta-analysis of randomized controlled trials.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS:<\/jats:title>\n            <jats:p>\n              We searched PubMed, Embase, Cochrane Central Register of Controlled Trials, and\n              <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/ClinicalTrials.gov\">ClinicalTrials.gov<\/jats:ext-link>\n              for randomized controlled trials comparing apixaban with aspirin for ischemic stroke prevention. Studies were excluded if no intracranial hemorrhage events were reported in either arm. In the primary analysis, we used the Mantel-Haenszel method to meta-analyze the relative risk of intracranial hemorrhage with apixaban versus aspirin therapy. We conducted sensitivity analyses to examine the strength of these findings and to examine the secondary outcome of hemorrhagic stroke (which excludes epidural and subdural hematomas).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS:<\/jats:title>\n            <jats:p>\n              Three randomized controlled trials met our inclusion criteria, comprising a total of 10\u2005626 patients and 74 incident intracranial hemorrhage events. In the pooled analysis, the relative risk of intracranial hemorrhage with apixaban versus aspirin therapy was 0.67 ([95% CI, 0.43\u20131.08];\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              =0.10). These findings were consistent in sensitivity analyses utilizing alternative statistical estimators, in analyses limited to primary prevention trials, and in analyses utilizing the outcome of hemorrhagic stroke (relative risk, 0.72 [95% CI, 0.39\u20131.31];\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              =0.28).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSIONS:<\/jats:title>\n            <jats:p>In randomized controlled trials evaluating ischemic stroke prevention, apixaban demonstrated a safety profile comparable\u2014and potentially superior\u2014to aspirin with respect to intracranial hemorrhage risk. These findings warrant a reconsideration of clinical practices that favor aspirin over apixaban due to concerns about intracranial hemorrhage risk.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/strokeaha.125.051088","type":"journal-article","created":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T05:00:14Z","timestamp":1749013214000},"page":"2318-2323","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":4,"title":["Risk of Intracranial Hemorrhage With Apixaban Versus Aspirin Therapy: A Meta-Analysis of Randomized Controlled Trials"],"prefix":"10.1161","volume":"56","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6924-0641","authenticated-orcid":true,"given":"Iyas","family":"Daghlas","sequence":"first","affiliation":[{"name":"Department of Neurology, UCSF Weill Institute for Neurosciences, University of California San Francisco (I.D., O.J.L., L.S., A.S.K., J.C.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0467-0875","authenticated-orcid":true,"given":"Ori J.","family":"Lieberman","sequence":"additional","affiliation":[{"name":"Department of Neurology, UCSF Weill Institute for Neurosciences, University of California San Francisco (I.D., O.J.L., L.S., A.S.K., J.C.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leena","family":"Suleiman","sequence":"additional","affiliation":[{"name":"Department of Neurology, UCSF Weill Institute for Neurosciences, University of California San Francisco (I.D., O.J.L., L.S., A.S.K., J.C.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8095-6517","authenticated-orcid":true,"given":"Anthony S.","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Neurology, UCSF Weill Institute for Neurosciences, University of California San Francisco (I.D., O.J.L., L.S., A.S.K., J.C.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4019-7525","authenticated-orcid":true,"given":"J. Claude","family":"Hemphill","sequence":"additional","affiliation":[{"name":"Department of Neurology, UCSF Weill Institute for Neurosciences, University of California San Francisco (I.D., O.J.L., L.S., A.S.K., J.C.H.)."},{"name":"Department of Neurology, Zuckerberg San Francisco General Hospital and Trauma Center, CA (J.C.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.j5058"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/STR.0000000000000407"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1024"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1177\/1747493020968424"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1802686"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2018.2215"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1813959"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1007432"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1056\/EVIDoa2300235"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2023.27188"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2310234"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2021.03.001"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1186\/2046-4053-2-80"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.l4898"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/sim.6301"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1055\/a-2496-5492"}],"container-title":["Stroke"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/STROKEAHA.125.051088","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T15:09:01Z","timestamp":1754579341000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/STROKEAHA.125.051088"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8]]},"references-count":16,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2025,8]]}},"alternative-id":["10.1161\/STROKEAHA.125.051088"],"URL":"https:\/\/doi.org\/10.1161\/strokeaha.125.051088","relation":{},"ISSN":["0039-2499","1524-4628"],"issn-type":[{"value":"0039-2499","type":"print"},{"value":"1524-4628","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8]]},"assertion":[{"value":"2025-02-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-11","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-28","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}