{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T22:12:41Z","timestamp":1792102361846,"version":"4.4.0"},"reference-count":41,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T00:00:00Z","timestamp":1755561600000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007914","name":"University of Texas Southwestern Medical Center","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007914","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Tenecteplase (TNK) is a novel thrombolytic agent gaining attention as an alternative to alteplase for treating acute ischemic stroke (AIS). This meta\u2010analysis evaluates the safety and efficacy of various TNK doses compared to alteplase, integrating recent randomized controlled trials (RCTs) and employing a frequentist network meta\u2010analysis to identify the optimal dose while addressing existing evidence gaps.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Up until December 2024, PubMed, Cochrane Central, and ScienceDirect were searched. Using Review Manager 5.4.1 for pairwise meta\u2010analysis, the Risk Ratios (RR) with 95% Confidence Intervals (CI) were pooled under the random effects model. Additionally, R version 4.3.2 and the \u201cnetmeta\u201d package were used to conduct a network meta\u2010analysis for various dosages of the two thrombolytic drugs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Thirteen RCTs, pooling 9,044 patients, were included in the quantitative synthesis. TNK was associated with a statistically significant improvement in the excellent functional outcome (mRS 0\u20131) (RR = 1.04; 95% CI: [1.00, 1.08]; p = 0.03) compared to alteplase. No significant differences were observed between TNK and alteplase in terms of good functional outcome (mRS 0\u20132), poor functional outcome (mRS 5\u20136), major neurological improvement within 72\u00a0h, symptomatic intracranial hemorrhage (sICH), or mortality at 90 days. On network analysis, TNK 0.25\u00a0mg\/kg showed significant improvement in excellent functional outcome (RR = 1.05, 95% CI: [1.01, 1.10]) and TNK 0.32\u00a0mg\/kg in good functional outcome (1.30, 95% CI: [1.15, 1.48]) compared to alteplase. According to the P\u2010score ranking, TNK 0.25\u00a0mg\/kg was ranked as the best for achieving an excellent outcome (P\u2010score = 0.86), and TNK 0.1\u00a0mg\/kg as the worst (P\u2010score = 0.16). For symptomatic intracranial hemorrhage (sICH), alteplase 0.9\u00a0mg\/kg was ranked as the best (P\u2010score = 0.71), and TNK 0.4\u00a0mg\/kg as the worst (P\u2010score = 0.17).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>TNK (0.25\u20100.32\u00a0mg\/kg) demonstrates superior efficacy compared to alteplase in achieving functional outcomes for AIS, while alteplase remains safer regarding sICH. Optimal dosing favors TNK 0.25\u00a0mg\/kg for efficacy, but safety considerations highlight the need for individualized thrombolytic selection.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/brb3.70756","type":"journal-article","created":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T10:37:41Z","timestamp":1755599861000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Comparative Efficacy and Safety of Different Tenecteplase Doses With Alteplase in Acute Ischemic Stroke: A Systematic Review With Pairwise and Network Meta\u2010Analysis to Determine the Optimal Dose"],"prefix":"10.1002","volume":"15","author":[{"given":"Muhammad Hassan","family":"Waseem","sequence":"first","affiliation":[{"name":"Allama Iqbal Medical College  Lahore Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-8990-7738","authenticated-orcid":false,"given":"Zain ul","family":"Abideen","sequence":"additional","affiliation":[{"name":"King Edward Medical University  Lahore Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad Haris","family":"Khan","sequence":"additional","affiliation":[{"name":"Saidu Medical College  Swat Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad Fawad","family":"Tahir","sequence":"additional","affiliation":[{"name":"H.B.S Medical and Dental College  Islamabad Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marium","family":"Khan","sequence":"additional","affiliation":[{"name":"Jinnah Sindh Medical University  Karachi Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hafsa Arshad Azam","family":"Raja","sequence":"additional","affiliation":[{"name":"Rawalpindi Medical University  Rawalpindi Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2508-4370","authenticated-orcid":false,"given":"Ameer Haider","family":"Cheema","sequence":"additional","affiliation":[{"name":"UT Southwestern Medical Center  Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sania","family":"Aimen","sequence":"additional","affiliation":[{"name":"Quetta Institute of Medical Sciences  Quetta Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad Arslan","family":"Tariq","sequence":"additional","affiliation":[{"name":"Allama Iqbal Medical College  Lahore Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2627-685X","authenticated-orcid":false,"given":"Javed","family":"Iqbal","sequence":"additional","affiliation":[{"name":"Nursing Department Hamad Medical Corporation  Doha Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8,19]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/S12883\u2010017\u20101007\u2010Y"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(22)00171\u20105"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMOA1716405"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMOA1414792"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(14)60584\u20105"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.7759\/CUREUS.46889"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.JCLINEPI.2010.04.026"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2024.08.014"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.109.572040\/SUPPL_FILE\/HALEY_707.PDF"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/9781119536604"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/BMJ.327.7414.557"},{"key":"e_1_2_11_13_1","doi-asserted-by":"crossref","unstructured":"Hu Y. 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