{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T20:55:33Z","timestamp":1788209733452,"version":"build-2803163510"},"reference-count":65,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,7]],"date-time":"2025-12-07T00:00:00Z","timestamp":1765065600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Acute ischemic stroke (AIS) is a leading cause of disability and death worldwide, requiring rapid reperfusion to minimize damage. Current treatments, including intravenous thrombolysis (IVT) with alteplase (rt-PA) and mechanical thrombectomy (MT), face limitations such as thrombolysis resistance, dosing complexity, and reduced efficacy in large vessel occlusions (LVOs) or fibrin-rich clots. Tenecteplase (TNK), a bioengineered thrombolytic agent with superior pharmacokinetics, simplified administration, and higher fibrin specificity, offers promising advantages over rt-PA, including potential synergy with MT and efficacy against resistant thrombi. Direct oral anticoagulants (DOACs) further complicate AIS management, but evidence suggests that DOAC-treated patients may experience better thrombolysis outcomes due to distinct thrombus characteristics. Advances in imaging now enable precise visualization of vessel occlusion and treatment effects, opening opportunities to refine therapies. Combination approaches targeting fibrin thrombus components may enhance thrombolysis and improve outcomes in resistant cases. Future research should explore TNK\u2019s role in intra-arterial (IA) applications, combination therapies, and its interaction with MT to optimize reperfusion strategies. TNK\u2019s simplified use and promising efficacy position it as a potential breakthrough in AIS management, with the potential to improve functional recovery and reduce treatment complexity.<\/jats:p>","DOI":"10.3390\/jcm14248675","type":"journal-article","created":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T16:20:29Z","timestamp":1765210829000},"page":"8675","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Thrombus Composition and the Evolving Role of Tenecteplase in Acute Ischemic Stroke"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9494-160X","authenticated-orcid":false,"given":"Senta","family":"Frol","sequence":"first","affiliation":[{"name":"Department of Vascular Neurology, University Medical Centre Ljubljana, Zalo\u0161ka cesta 2, 1000 Ljubljana, Slovenia"},{"name":"Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matija","family":"Zupan","sequence":"additional","affiliation":[{"name":"Department of Vascular Neurology, University Medical Centre Ljubljana, Zalo\u0161ka cesta 2, 1000 Ljubljana, Slovenia"},{"name":"Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"I","DOI":"10.1177\/2396987321989865","article-title":"European Stroke Organisation (ESO) guidelines on intravenous thrombolysis for acute ischaemic stroke","volume":"6","author":"Berge","year":"2021","journal-title":"Eur. Stroke J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e344","DOI":"10.1161\/STR.0000000000000211","article-title":"Guidelines for the Early Management of Patients with Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association\/American Stroke Association","volume":"50","author":"Powers","year":"2019","journal-title":"Stroke"},{"key":"ref_3","first-page":"81","article-title":"Hemorrhagic transformation after cerebral infarction: Current concepts and challenges","volume":"2","author":"Zhang","year":"2014","journal-title":"Ann. Transl. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2688","DOI":"10.1161\/STROKEAHA.123.044123","article-title":"Neurovascular Inflammation and Complications of Thrombolysis Therapy in Stroke","volume":"54","author":"Liu","year":"2023","journal-title":"Stroke"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Desilles, J.P., Di Meglio, L., Delvoye, F., Ma\u00efer, B., Piotin, M., Ho-Tin-No\u00e9, B., and Mazighi, M. (2022). Composition and Organization of Acute Ischemic Stroke Thrombus: A Wealth of Information for Future Thrombolytic Strategies. Front. Neurol., 13.","DOI":"10.3389\/fneur.2022.870331"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"100178","DOI":"10.1016\/j.rpth.2023.100178","article-title":"Thrombus composition and thrombolysis resistance in stroke","volume":"7","author":"Desilles","year":"2023","journal-title":"Res. Pract. Thromb. Haemost."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1007\/s11239-025-03074-6","article-title":"Thrombus composition in ischaemic stroke: Histological and radiological evaluation, and implications for acute clinical management","volume":"58","author":"Dohle","year":"2025","journal-title":"J. Thromb. Thrombolysis"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2206","DOI":"10.1161\/STROKEAHA.117.016590","article-title":"Ischemic stroke: What does the histological composition tell us about the origin of the thrombus?","volume":"48","author":"Sporns","year":"2017","journal-title":"Stroke"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1007\/s00234-023-03115-y","article-title":"Association between thrombus composition and stroke etiology in the Mr Clean registry biobank","volume":"65","author":"Hund","year":"2023","journal-title":"Neuroradiology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"498","DOI":"10.3324\/haematol.2019.219881","article-title":"Structural analysis of ischemic stroke thrombi: Histological indications for therapy resistance","volume":"105","author":"Staessens","year":"2020","journal-title":"Haematologica"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1016\/j.neurad.2023.01.004","article-title":"Spatial heterogeneity of occlusive thrombus in acute ischemic stroke: A systematic review","volume":"50","author":"Reymond","year":"2023","journal-title":"J. Neuroradiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"57","DOI":"10.3174\/ajnr.A6866","article-title":"Increased Perviousness on CT for Acute Ischemic Stroke is Associated with Fibrin\/Platelet-Rich Clots","volume":"42","author":"Patel","year":"2021","journal-title":"AJNR Am. J. Neuroradiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"101848","DOI":"10.1016\/j.nuclcard.2024.101848","article-title":"Translational molecular imaging: Thrombosis imaging with positron emission tomography","volume":"39","author":"Balmforth","year":"2024","journal-title":"J. Nucl. Cardiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1161\/STROKEAHA.120.032810","article-title":"Thrombus Composition and Efficacy of Thrombolysis and Thrombectomy in Acute Ischemic Stroke","volume":"52","author":"Jolugbo","year":"2021","journal-title":"Stroke"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1055\/s-0038-1648189","article-title":"The influence of transport parameters and enzyme kinetics of the fibrinolytic system on thrombolysis: Mathematical modelling of two idealised cases","volume":"65","author":"Zidansek","year":"1991","journal-title":"Thromb. Haemost."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1001\/jamaneurol.2022.4782","article-title":"Intravenous Thrombolysis in Patients With Ischemic Stroke and Recent Ingestion of Direct Oral Anticoagulants","volume":"80","author":"Meinel","year":"2023","journal-title":"JAMA Neurol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1177\/23969873241252751","article-title":"Intravenous thrombolysis in patients with recent intake of direct oral anticoagulants: A target trial analysis after the liberalization of institutional guidelines","volume":"9","author":"Jung","year":"2024","journal-title":"Eur. Stroke J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1001\/jama.2022.0948","article-title":"Association of Recent Use of Non-Vitamin K Antagonist Oral Anticoagulants With Intracranial Hemorrhage Among Patients With Acute Ischemic Stroke Treated With Alteplase","volume":"327","author":"Kam","year":"2022","journal-title":"JAMA"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Ikenberg, B., Boeckh-Behrens, T., Maegerlein, C., H\u00e4rtl, J., Hernandez Petzsche, M., Zimmer, C., Wunderlich, S., and Berndt, M. (2022). Ischemic Stroke of Suspected Cardioembolic Origin Despite Anticoagulation: Does Thrombus Analysis Help to Clarify Etiology?. Front. Neurol., 13.","DOI":"10.3389\/fneur.2022.824792"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1016\/j.jstrokecerebrovasdis.2018.11.019","article-title":"Intravenous Thrombolysis After Idarucizumab Application in Acute Stroke Patients-A Potentially Increased Sensitivity of Thrombi to Lysis?","volume":"28","author":"Sabovic","year":"2019","journal-title":"J. Stroke Cerebrovasc. Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/BJ20100965","article-title":"Proteases as therapeutics","volume":"435","author":"Craik","year":"2011","journal-title":"Biochem. J."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3670","DOI":"10.1073\/pnas.91.9.3670","article-title":"A faster-acting and more potent form of tissue plasminogen activator","volume":"91","author":"Keyt","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1007\/s13311-023-01391-3","article-title":"Evolving Thrombolytics: From Alteplase to Tenecteplase","volume":"20","author":"Miller","year":"2023","journal-title":"Neurotherapeutics"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3543","DOI":"10.1161\/STROKEAHA.115.011290","article-title":"Coagulation and Fibrinolytic Activity of Tenecteplase and Alteplase in Acute Ischemic Stroke","volume":"46","author":"Huang","year":"2015","journal-title":"Stroke"},{"key":"ref_25","first-page":"90","article-title":"Improved Door-to-Needle Time After Implementation of Tenecteplase as the Preferred Thrombolytic for Acute Ischemic Stroke at a Large Community Teaching Hospital Emergency Department","volume":"11","author":"Henderson","year":"2024","journal-title":"Hosp. Pharm."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/s42466-025-00388-x","article-title":"Switch to tenecteplase for intravenous thrombolysis in stroke patients: Experience from a German high-volume stroke center","volume":"7","author":"Sekita","year":"2025","journal-title":"Neurol. Res. Pract."},{"key":"ref_27","first-page":"e000102","article-title":"Tenecteplase Improves Door-to-Needle Time in Real-World Acute Stroke Treatment","volume":"1","author":"Hall","year":"2021","journal-title":"Stroke Vasc. Interv. Neurol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1056\/NEJMoa1109842","article-title":"A randomized trial of tenecteplase versus alteplase for acute ischemic stroke","volume":"366","author":"Parsons","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1016\/S1474-4422(15)70017-7","article-title":"Alteplase versus tenecteplase for thrombolysis after ischaemic stroke (ATTEST): A phase 2, randomised, open-label, blinded endpoint study","volume":"14","author":"Huang","year":"2015","journal-title":"Lancet Neurol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1016\/S1474-4422(17)30253-3","article-title":"Tenecteplase versus alteplase for management of acute ischaemic stroke (NOR-TEST): A phase 3, randomised, open-label, blinded endpoint trial","volume":"16","author":"Logallo","year":"2017","journal-title":"Lancet Neurol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1136\/svn-2021-000978","article-title":"Safety and efficacy of tenecteplase versus alteplase in patients with acute ischaemic stroke (TRACE): A multicentre, randomised, open label, blinded-endpoint (PROBE) controlled phase II study","volume":"7","author":"Li","year":"2022","journal-title":"Stroke Vasc. Neurol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/S0140-6736(22)01054-6","article-title":"AcT Trial Investigators. Intravenous tenecteplase compared with alteplase for acute ischaemic stroke in Canada (AcT): A pragmatic, multicentre, open-label, registry-linked, randomised, controlled, non-inferiority trial","volume":"400","author":"Menon","year":"2022","journal-title":"Lancet"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1016\/S0140-6736(22)02600-9","article-title":"TRACE-2 Investigators. Tenecteplase versus alteplase in acute ischaemic cerebrovascular events (TRACE-2): A phase 3, multicentre, open-label, randomised controlled, non-inferiority trial","volume":"401","author":"Wang","year":"2023","journal-title":"Lancet"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1001\/jama.2024.14721","article-title":"Tenecteplase vs. Alteplase for Patients with Acute Ischemic Stroke: The ORIGINAL Randomized Clinical Trial","volume":"332","author":"Meng","year":"2024","journal-title":"JAMA"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1016\/S1474-4422(24)00206-0","article-title":"TASTE Investigators. Tenecteplase versus alteplase for thrombolysis in patients selected by use of perfusion imaging within 4\u00b75 h of onset of ischaemic stroke (TASTE): A multicentre, randomised, controlled, phase 3 non-inferiority trial","volume":"23","author":"Parsons","year":"2024","journal-title":"Lancet Neurol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1016\/S1474-4422(24)00377-6","article-title":"Tenecteplase versus alteplase for acute stroke within 4\u00b75 h of onset (ATTEST-2): A randomised, parallel group, open-label trial","volume":"23","author":"Muir","year":"2024","journal-title":"Lancet Neurol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.1056\/NEJMoa1716405","article-title":"EXTEND-IA TNK Investigators. Tenecteplase versus Alteplase before Thrombectomy for Ischemic Stroke","volume":"378","author":"Campbell","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1056\/NEJMoa2310392","article-title":"TIMELESS Investigators. Tenecteplase for Stroke at 4.5 to 24 Hours with Perfusion-Imaging Selection","volume":"390","author":"Albers","year":"2024","journal-title":"N. Engl. J. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1016\/S1474-4422(22)00124-7","article-title":"Tenecteplase versus alteplase for the management of acute ischaemic stroke in Norway (NOR-TEST 2, part A): A phase 3, randomised, open-label, blinded endpoint, non-inferiority trial","volume":"21","author":"Kvistad","year":"2022","journal-title":"Lancet Neurol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e10459","DOI":"10.48101\/ujms.v129.10459","article-title":"Tenecteplase compared to alteplase in real-world outcome: A Swedish Stroke Register study","volume":"129","author":"Eriksson","year":"2024","journal-title":"Upsala J. Med. Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1016\/j.annemergmed.2023.03.022","article-title":"Tenecteplase Versus Alteplase for Acute Stroke: Mortality and Bleeding Complications","volume":"82","author":"Murphy","year":"2023","journal-title":"Ann. Emerg. Med."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Yao, Y., Wu, Y., Zhang, X., Liu, C., Cai, L., Ying, Y., and Yang, J. (2024). Real-world data of tenecteplase vs. alteplase in the treatment of acute ischemic stroke: A single-center analysis. Front. Neurol., 15.","DOI":"10.3389\/fneur.2024.1386386"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Zhao, W., Zhang, X., Zhao, Y., Zhao, R., and Liu, Y. (2025). Comparative effectiveness and safety of tenecteplase versus alteplase for intravenous thrombolysis in acute ischemic stroke: A retrospective study. Front. Neurol., 16.","DOI":"10.3389\/fneur.2025.1691168"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e250548","DOI":"10.1001\/jamanetworkopen.2025.0548","article-title":"Short-Term Safety and Effectiveness for Tenecteplase and Alteplase in Acute Ischemic Stroke","volume":"8","author":"Rousseau","year":"2025","journal-title":"JAMA Netw. Open"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1002\/ana.26445","article-title":"Intravenous Thrombolysis with Tenecteplase for the Treatment of Acute Ischemic Stroke","volume":"92","author":"Tsivgoulis","year":"2022","journal-title":"Ann. Neurol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1001\/jama.2022.1645","article-title":"CHOICE Investigators. Effect of intra-arterial alteplase vs. placebo following successful thrombectomy on functional outcomes in patients with large vessel occlusion acute ischemic stroke","volume":"327","author":"Blasco","year":"2022","journal-title":"JAMA"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1097\/MBC.0000000000001309","article-title":"The impact of von Willebrand factor on fibrin formation and structure unveiled with type 3 von Willebrand disease plasma","volume":"35","author":"Courson","year":"2024","journal-title":"Blood Coagul. Fibrinolysis"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1182\/blood.2023021915","article-title":"Novel functions for von Willebrand factor","volume":"144","author":"Atiq","year":"2024","journal-title":"Blood"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2536","DOI":"10.1161\/STROKEAHA.124.045755","article-title":"Emerging Adjuvant Thrombolytic Therapies for Acute Ischemic Stroke Reperfusion","volume":"55","author":"Yogendrakumar","year":"2024","journal-title":"Stroke"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1161\/STROKEAHA.123.045880","article-title":"R-tPA resistance is specific for platelet-rich stroke thrombi and can be overcome by targeting nonfibrin components","volume":"55","author":"Vandelanotte","year":"2024","journal-title":"Stroke"},{"key":"ref_51","first-page":"e1686","article-title":"Acute ischemic stroke thrombi have an outer shell that impairs fibrinolysis","volume":"93","author":"Desilles","year":"2019","journal-title":"Neurology"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1161\/STROKEAHA.123.045225","article-title":"Neutrophil Extracellular Traps and Thrombolysis Resistance: New Insights for Targeting Therapies","volume":"55","author":"Mengozzi","year":"2024","journal-title":"Stroke"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Desilles, J.-P., Nomenjanahary, M.S., Perrot, A., Di Meglio, L., Zemali, F., Zalghout, S., Loyau, S., Labreuche, J., Bourrienne, M.-C., and Faille, D. (2025). The compoCLOT Study Group. Neutrophil extracellular traps block endogenous and intravenous thrombolysis-induced fibrinolysis in large vessel occlusion acute ischemic stroke. bioRxiv.","DOI":"10.1101\/2025.03.28.646062"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1055\/s-0040-1718760","article-title":"Extracellular Histones Inhibit Fibrinolysis through Noncovalent and Covalent Interactions with Fibrin","volume":"121","author":"Locke","year":"2021","journal-title":"Thromb. Haemost."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Huang, G., Wu, H., Lin, B., Deng, D., Liu, Y., Qu, J., Xu, J., and Wang, B. (Semin. Thromb. Hemost., 2025). Targeting Neutrophil Extracellular Traps: A New Strategy for the Treatment of Acute Ischemic Stroke Based on Thrombolysis Resistance, Semin. Thromb. Hemost., online.","DOI":"10.1055\/a-2609-3457"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Li, Q., Ye, J., Li, Z., Xiao, Q., Tan, S., Hu, B., and Jin, H. (2024). The role of neutrophils in tPA thrombolysis after stroke: A malicious troublemaker. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1477669"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2381","DOI":"10.1161\/STROKEAHA.113.001059","article-title":"Combined approach to lysis utilizing eptifibatide and recombinant tissue plasminogen activator in acute ischemic stroke-enhanced regimen stroke trial","volume":"44","author":"Pancioli","year":"2013","journal-title":"Stroke"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1161\/STROKEAHA.111.625574","article-title":"The argatroban and tissue-type plasminogen activator stroke study: Final results of a pilot safety study","volume":"43","author":"Barreto","year":"2012","journal-title":"Stroke"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1981","DOI":"10.1056\/NEJMoa2001123","article-title":"Endovascular Thrombectomy with or without Intravenous Alteplase in Acute Stroke","volume":"382","author":"Yang","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1001\/jama.2020.23523","article-title":"Effect of Endovascular Treatment Alone vs. Intravenous Alteplase Plus Endovascular Treatment on Functional Independence in Patients With Acute Ischemic Stroke: The DEVT Randomized Clinical Trial","volume":"325","author":"Zi","year":"2021","journal-title":"JAMA"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/S0140-6736(22)00537-2","article-title":"Thrombectomy alone versus intravenous alteplase plus thrombectomy in patients with stroke: An open-label, blinded-outcome, randomised non-inferiority trial","volume":"400","author":"Fischer","year":"2022","journal-title":"Lancet"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1833","DOI":"10.1056\/NEJMoa2107727","article-title":"A Randomized Trial of Intravenous Alteplase before Endovascular Treatment for Stroke","volume":"385","author":"LeCouffe","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"107177","DOI":"10.1016\/j.vph.2023.107177","article-title":"Endovascular thrombectomy with or without intravenous thrombolysis in large-vessel ischemic stroke: A non-inferiority meta-analysis of 6 randomised controlled trials","volume":"150","author":"Horvath","year":"2023","journal-title":"Vasc. Pharmacol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1001\/jama.2024.0589","article-title":"Time to Treatment With Intravenous Thrombolysis Before Thrombectomy and Functional Outcomes in Acute Ischemic Stroke: A Meta-Analysis","volume":"31","author":"Kaesmacher","year":"2024","journal-title":"JAMA"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1136\/jnis-2024-022585","article-title":"The evolution of tenecteplase as a bridging agent for acute ischemic stroke","volume":"17","author":"Frol","year":"2025","journal-title":"J. Neurointerv. Surg."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/24\/8675\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T05:11:31Z","timestamp":1765343491000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/24\/8675"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,7]]},"references-count":65,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["jcm14248675"],"URL":"https:\/\/doi.org\/10.3390\/jcm14248675","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,7]]}}}