{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T04:14:14Z","timestamp":1793506454861,"version":"4.5.0"},"reference-count":23,"publisher":"American Medical Association (AMA)","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA"],"published-print":{"date-parts":[[2025,9,2]]},"abstract":"Importance<\/jats:title>The safety and efficacy of intravenous thrombolytics beyond 4.5 hours after ischemic stroke onset remain inadequately studied.<\/jats:p><\/jats:sec>Objective<\/jats:title>To evaluate the safety and efficacy of intravenous alteplase administered 4.5 to 24 hours after stroke onset in patients with salvageable brain tissue, regardless of the presence of large vessel occlusion.<\/jats:p><\/jats:sec>Design, Setting, and Participants<\/jats:title>This randomized, open-label, blinded end-point trial was conducted at 26 stroke centers across China. A total of 372 patients with acute ischemic stroke and salvageable brain tissue identified by perfusion imaging were enrolled between June 21, 2021, and June 30, 2024 (final follow-up October 2, 2024). Eligibility criteria included stroke onset (or the midpoint between last known well and symptom recognition if onset was unknown) of 4.5 to 24 hours prior to presentation, and no initial plan for endovascular thrombectomy. Data were analyzed from December 2024 to February 2025.<\/jats:p><\/jats:sec>Interventions<\/jats:title>Patients were randomly assigned (1:1) using a minimization algorithm to receive intravenous alteplase (0.9 mg\/kg; maximum dose, 90 mg; n\u2009=\u2009186) or standard medical treatment (n\u2009=\u2009186).<\/jats:p><\/jats:sec>Main Outcomes and Measures<\/jats:title>The primary efficacy outcome was functional independence, defined as a modified Rankin Scale score of 0 to 1 at 90 days. Safety outcomes included symptomatic intracranial hemorrhage within 36 hours and all-cause mortality within 90 days.<\/jats:p><\/jats:sec>Results<\/jats:title>Among 372 patients who were enrolled (median [IQR] age, 72 [64-80] years; 160 [43%] women), all completed the trial. The primary outcome occurred in 75 of 186 patients (40%) in the alteplase group and 49 of 186 (26%) in the control group (adjusted risk ratio, 1.52 [95% CI, 1.14-2.02]; P<\/jats:italic>\u2009=\u2009.004; unadjusted risk difference, 13.98% [95% CI, 4.50%-23.45%]). The incidence of symptomatic intracranial hemorrhage was higher with alteplase at 3.8% compared with 0.51% with standard treatment (adjusted risk ratio, 7.34 [95% CI, 1.54-34.84]; P<\/jats:italic>\u2009=\u2009.01; unadjusted risk difference, 3.23% [0.28%-6.19%]), and mortality was 11% in both groups (adjusted risk ratio, 0.91 [95% CI, 0.52-1.62]; P<\/jats:italic>\u2009=\u2009.76; unadjusted risk difference, 0% [95% CI, \u22126.30% to 6.30%]).<\/jats:p><\/jats:sec>Conclusions and Relevance<\/jats:title>In patients with acute ischemic stroke with salvageable brain tissue identified by perfusion imaging who did not initially receive thrombectomy, intravenous alteplase administered 4.5 to 24 hours after onset provided functional benefit, despite an increase in symptomatic intracranial hemorrhage.<\/jats:p><\/jats:sec>Trial Registration<\/jats:title>ClinicalTrials.gov Identifier: NCT04879615<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1001\/jama.2025.12063","type":"journal-article","created":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T15:31:06Z","timestamp":1754580666000},"page":"788","source":"Crossref","is-referenced-by-count":74,"title":["Alteplase for Acute Ischemic Stroke at 4.5 to 24 Hours"],"prefix":"10.1001","volume":"334","author":[{"given":"Ying","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Neurology, the Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, China"},{"name":"State Key Laboratory of Transvascular Implantation Devices, Hangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaode","family":"He","sequence":"additional","affiliation":[{"name":"Department of Neurology, the Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, China"},{"name":"State Key Laboratory of Transvascular Implantation Devices, Hangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce C. 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