{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T08:03:35Z","timestamp":1771315415254,"version":"3.50.1"},"reference-count":59,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T00:00:00Z","timestamp":1764460800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T00:00:00Z","timestamp":1764460800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:p>\n                    Pretreatment with direct oral anticoagulants (DOACs) may increase bleeding risk after intravenous thrombolysis (IVT) for acute ischemic stroke, but the comparative safety of tenecteplase vs. alteplase remains uncertain. We conducted a real\u2010world retrospective cohort study using the TriNetX Global Network (queried October 2025). Patients with acute ischemic stroke who received IVT were identified and matched 1:1 by propensity scores. Cox proportional hazard models estimated hazard ratios (HRs); a time\u2010split Cox model assessed time\u2010varying effects. The primary composite outcome comprised nontraumatic intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH), transfusion, gastrointestinal bleeding, and mortality; secondary outcomes were the individual components. Outcomes were assessed from the day of IVT through days 1, 7, 14, and 21. A total of 1636 patients receiving tenecteplase and 25,370 receiving alteplase were identified, yielding 1634 matched patients per group. Tenecteplase was associated with higher risks of composite outcomes (Day 1: 13.6% vs. 7.4%; HR 1.87,\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.001; Day 21: HR 1.36,\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.002), ICH (Day 1: 9.1% vs 2.8%; HR 3.26,\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.001; Day 21: HR 3.23,\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.001), SAH (Day 1: 3.2% vs 1.1%; HR 2.84,\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.001; Day 21: HR 2.78,\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.001). Mortality was greater with tenecteplase at Day 1 (2.6% vs 1.3%; HR 2.01,\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.009) and Day 7 (HR 1.38,\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.020). Time\u2010split Cox analysis confirmed that excess risk was confined to the first 24\u2009hours. Among patients pretreated with\n                    <jats:styled-content style=\"fixed-case\">DOACs<\/jats:styled-content>\n                    , tenecteplase was associated with higher early risk of hemorrhagic transformation and mortality than alteplase, underscoring the need for vigilance during the first 24\u2009hours after treatment.\n                  <\/jats:p>","DOI":"10.1002\/cpt.70151","type":"journal-article","created":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T08:14:23Z","timestamp":1764576863000},"page":"763-772","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Comparative Safety of Tenecteplase and Alteplase in Direct Oral Anticoagulant\u2010Pretreated Patients With Acute Ischemic Stroke"],"prefix":"10.1002","volume":"119","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-4774-0627","authenticated-orcid":false,"given":"Hsu\u2010Wei","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Epidemiology Harvard T.H. Chan School of Public Health  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4485-3114","authenticated-orcid":false,"given":"Pin\u2010Jung","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Epidemiology Harvard T.H. Chan School of Public Health  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0661-173X","authenticated-orcid":false,"given":"Hui\u2010An","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, School of Medicine, College of Medicine Taipei Medical University  Taipei Taiwan"},{"name":"Department of Emergency Medicine Taipei Medical University Hospital  Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0470-2184","authenticated-orcid":false,"given":"Sheng\u2010Feng","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine Taipei Medical University Hospital  Taipei Taiwan"},{"name":"Department of Public Health, School of Medicine, College of Medicine Taipei Medical University  Taipei Taiwan"},{"name":"School of Public Health, College of Public Health Taipei Medical University  Taipei Taiwan"},{"name":"Center of Evidence\u2010Based Medicine Taipei Medical University Hospital  Taipei Taiwan"},{"name":"Department of Medical Research Taipei Medical University Hospital  Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,11,30]]},"reference":[{"key":"e_1_2_14_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(24)00367-2"},{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(24)00369-7"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-023-01391-3"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2024.14721"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-022-11242-4"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2024.1386386"},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(24)00206-0"},{"key":"e_1_2_14_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vph.2005.09.003"},{"key":"e_1_2_14_9_1","doi-asserted-by":"publisher","DOI":"10.2147\/NDT.S360967"},{"key":"e_1_2_14_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40263-015-0307-2"},{"key":"e_1_2_14_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1716405"},{"key":"e_1_2_14_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1414792"},{"key":"e_1_2_14_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)01054-6"},{"key":"e_1_2_14_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)02600-9"},{"key":"e_1_2_14_15_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.120.029749"},{"key":"e_1_2_14_16_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.118.022606"},{"key":"e_1_2_14_17_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200241150-00001"},{"key":"e_1_2_14_18_1","doi-asserted-by":"publisher","DOI":"10.1592\/phco.21.2.207.34103"},{"key":"e_1_2_14_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(99)07403-6"},{"key":"e_1_2_14_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0149-2918(01)80086-2"},{"key":"e_1_2_14_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annemergmed.2023.03.022"},{"key":"e_1_2_14_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2022.120537"},{"key":"e_1_2_14_23_1","unstructured":"Muir K.et al.Randomised Trial of Tenectplase Versus Alteplase for Acute Stroke within 4.5 h of Onset: The Second Alteplase\u2010Tenecteplase Trial Evaluation for Stroke Thrombolysis (ATTEST\u20102)."},{"key":"e_1_2_14_24_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2023.1102463"},{"key":"e_1_2_14_25_1","article-title":"A systematic review of the efficacy and safety of tenecteplase versus alteplase in acute ischemic stroke: a time to pass the torch","volume":"4","author":"Rodriguez M.","year":"2024","journal-title":"Stroke Vasc. 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