{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T06:49:07Z","timestamp":1774594147808,"version":"3.50.1"},"reference-count":49,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T00:00:00Z","timestamp":1774569600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Although several newer thrombolytic agents for acute ischemic stroke (AIS) within 4.5\u202fh of onset have been developed, their relative efficacy, safety, and optimal dosing remain unclear. A comprehensive comparison across all available agents is therefore needed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We systematically searched PubMed, Embase, the Cochrane Central Register of Controlled Trials, and Web of Science for English-language reports of randomized controlled trials (RCTs) published up to December 12, 2025. Eligible trials enrolled adult AIS patients treated with intravenous thrombolysis. Primary outcomes were 90-day excellent (modified Rankin Scale [mRS] score 0\u20131) and good (mRS 0\u20132) functional outcomes. Safety outcomes were symptomatic intracranial hemorrhage (sICH), and all-cause mortality. A frequentist network meta-analysis using a fixed-effect consistency model was conducted to estimate odds ratios (ORs) with 95% confidence intervals (CIs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 21 RCTs involving 16,837 patients were included. For achieving mRS 0\u20131, reteplase (18\u202f+\u202f18\u202fmg) showed a statistically significant advantage over alteplase (0.9\u202fmg\/kg) (OR 1.60; 95% CI, 1.27\u20132.02), and non-immunogenic recombinant staphylokinase (10\u202fmg) demonstrated a statistically significant benefit (OR 2.23; 95% CI, 1.43\u20133.48). Reteplase (18\u202f+\u202f18\u202fmg) also improved the likelihood of mRS 0\u20132 compared with alteplase (OR 1.41; 95% CI, 1.08\u20131.84). For safety, non-immunogenic recombinant staphylokinase significantly reduced sICH risk compared with tenecteplase 0.25\u202fmg\/kg (OR 0.31; 95% CI, 0.11\u20130.94). No significant differences in 90-day mortality were observed among treatments.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Within the 4.5-h treatment window, reteplase (18\u202f+\u202f18\u202fmg) and non-immunogenic recombinant staphylokinase (10\u202fmg) were associated with the highest probabilities of improved functional outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Systematic review registration<\/jats:title>\n                    <jats:p>\n                      <jats:uri>https:\/\/www.crd.york.ac.uk\/PROSPERO\/view\/CRD420251152754<\/jats:uri>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fneur.2026.1775325","type":"journal-article","created":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T05:19:50Z","timestamp":1774588790000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Comparison of the efficacy and safety of different thrombolytic drugs in the treatment of acute ischemic stroke within 4.5\u202fh: a systematic review and network meta-analysis"],"prefix":"10.3389","volume":"17","author":[{"given":"Xinmin","family":"Yu","sequence":"first","affiliation":[{"name":"Graduate School, Shanghai University of Traditional Chinese Medicine","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiale","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Clinical Medicine, Shanghai University of Medicine and Health Sciences","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chenlei","family":"Shi","sequence":"additional","affiliation":[{"name":"School of Clinical Medicine, Shanghai University of Medicine and Health Sciences","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Degang","family":"Xue","sequence":"additional","affiliation":[{"name":"Department of Cardiology, General Hospital of Fushun Mining Bureau of Liaoning Health Industry","place":["Fushun, Liaoning, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuting","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, General Hospital of Fushun Mining Bureau of Liaoning Health Industry","place":["Fushun, Liaoning, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weiwei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Public Health, Jinshan Central Hospital Affiliated to Shanghai University of Medicine and Health Sciences","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miaomiao","family":"Zhao","sequence":"additional","affiliation":[{"name":"School of Clinical Medicine, Shanghai University of Medicine and Health Sciences","place":["Shanghai, China"]},{"name":"Shanghai University of Traditional Chinese Medicine","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,27]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"e16481","DOI":"10.1111\/ene.16481","article-title":"Global, regional, and National Epidemiology of ischemic stroke from 1990 to 2021","volume":"31","author":"Hou","year":"2024","journal-title":"Eur J Neurol"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1474","DOI":"10.1007\/s12975-024-01319-9","article-title":"Global and regional burden of ischemic stroke disease from 1990 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randomised, open-label, blinded endpoint study","volume":"14","author":"Huang","year":"2015","journal-title":"Lancet Neurol"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"520","DOI":"10.1016\/s1474-4422(22)00171-5","article-title":"Comparison of tenecteplase with alteplase for the early treatment of ischaemic stroke in the Melbourne Mobile stroke unit (taste-a): a phase 2, randomised, open-label trial","volume":"21","author":"Bivard","year":"2022","journal-title":"Lancet Neurol"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"2313","DOI":"10.1056\/NEJMoa1515510","article-title":"Low-dose versus standard-dose intravenous alteplase in acute ischemic stroke","volume":"374","author":"Anderson","year":"2016","journal-title":"N Engl J Med"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"2766","DOI":"10.1161\/strokeaha.123.044267","article-title":"Effect of time to thrombolysis on clinical outcomes in patients with acute ischemic stroke treated with 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Tissue plasminogen activator for acute ischemic stroke","volume":"333","year":"1995","journal-title":"N Engl J Med"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"628","DOI":"10.1016\/s0140-6736(15)61478-7","article-title":"Network Meta-analysis: a norm for comparative effectiveness?","volume":"386","author":"Higgins","year":"2015","journal-title":"Lancet"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"e1003082","DOI":"10.1371\/journal.pmed.1003082","article-title":"Cinema: an approach for assessing confidence in the results of a network Meta-analysis","volume":"17","author":"Nikolakopoulou","year":"2020","journal-title":"PLoS Med"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"e1080","DOI":"10.1002\/cl2.1080","article-title":"Cinema: software for Semiautomated assessment of the confidence in the results of network Meta-analysis","volume":"16","author":"Papakonstantinou","year":"2020","journal-title":"Campbell Syst 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