Safety Outcomes Following Intravenous Thrombolysis in Acute Ischemic Stroke: A Systematic Review and Network Meta-analysis

Collaborators GBDS. Global, regional, and national burden of stroke and its risk factors, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet Neurol. 2021;20(10):795–820.

Article  Google Scholar 

Goldstein JN, Marrero M, Masrur S, Pervez M, Barrocas AM, Abdullah A, et al. Management of thrombolysis-associated symptomatic intracerebral hemorrhage. Arch Neurol. 2010;67(8):965–9.

Article  PubMed  PubMed Central  Google Scholar 

Yaghi S, Eisenberger A, Willey JZ. Symptomatic intracerebral hemorrhage in acute ischemic stroke after thrombolysis with intravenous recombinant tissue plasminogen activator: a review of natural history and treatment. JAMA Neurol. 2014;71(9):1181–5.

Article  PubMed  PubMed Central  Google Scholar 

Strbian D, Sairanen T, Meretoja A, Pitkaniemi J, Putaala J, Salonen O, et al. Patient outcomes from symptomatic intracerebral hemorrhage after stroke thrombolysis. Neurology. 2011;77(4):341–8.

Article  PubMed  CAS  Google Scholar 

National Institute of Neurological, Stroke rt PASSG. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med. 1995;333(24):1581–7.

Article  Google Scholar 

Wang Y, Li S, Pan Y, Li H, Parsons MW, Campbell BCV, et al. Tenecteplase versus alteplase in acute ischaemic cerebrovascular events (TRACE-2): a phase 3, multicentre, open-label, randomised controlled, non-inferiority trial. Lancet. 2023;401(10377):645–54.

Article  PubMed  CAS  Google Scholar 

Albers GW, Jumaa M, Purdon B, Zaidi SF, Streib C, Shuaib A, et al. Tenecteplase for stroke at 4.5 to 24 hours with perfusion-imaging selection. N Engl J Med. 2024;390(8):701–11.

Article  PubMed  CAS  Google Scholar 

Li Y, Cui R, Fan F, Lu Y, Ai Y, Liu H, et al. The efficacy and safety of ischemic stroke therapies: an umbrella review. Front Pharmacol. 2022;13:924747.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Palaiodimou L, Katsanos AH, Turc G, Romoli M, Theodorou A, Lemmens R, et al. Tenecteplase for the treatment of acute ischemic stroke in the extended time window: a systematic review and meta-analysis. Ther Adv Neurol Disord. 2024;17:17562864231221324.

Article  PubMed  PubMed Central  Google Scholar 

Rouse B, Chaimani A, Li T. Network meta-analysis: an introduction for clinicians. Intern Emerg Med. 2017;12(1):103–11.

Article  PubMed  Google Scholar 

Hu Y, Wu S, Zhang H, Wang K, Zhang L, Ma Y, et al. Efficacy and safety of various intravenous thrombolytics for acute ischemic stroke (AIS) at various dosages: a systematic review and network meta-analysis. Neurol Ther. 2025;14(2):491–523.

Article  PubMed  Google Scholar 

Shahid S, Saeed H, Iqbal M, Batool A, Masood MB, Ahmad MH, et al. Comparative efficacy and safety of tissue plasminogen activators (tPA) in acute ischemic stroke: a systematic review and network meta-analysis of randomized controlled trials. J Stroke Cerebrovasc Dis. 2025;34(3):108230.

Article  PubMed  Google Scholar 

Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. Rev Esp Cardiol (Engl Ed). 2021;74(9):790–9.

Article  PubMed  Google Scholar 

Agency EM. 1. GLOSSARY. International Council for Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use Good Clinical Practice (ICH GCP). 2018. https://ichgcp.net/1-glossary. Accessed 26 Mar 2025.

Seet RC, Rabinstein AA. Symptomatic intracranial hemorrhage following intravenous thrombolysis for acute ischemic stroke: a critical review of case definitions. Cerebrovasc Dis. 2012;34(2):106–14.

Article  PubMed  Google Scholar 

Wahlgren N, Ahmed N, Davalos A, Ford GA, Grond M, Hacke W, et al. Thrombolysis with alteplase for acute ischaemic stroke in the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST): an observational study. Lancet. 2007;369(9558):275–82.

Article  PubMed  CAS  Google Scholar 

Brown EG, Wood L, Wood S. The medical dictionary for regulatory activities (MedDRA). Drug Saf. 1999;20(2):109–17.

Article  PubMed  CAS  Google Scholar 

Sterne JAC, Savovic J, Page MJ, Elbers RG, Blencowe NS, Boutron I, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019;366:l4898.

Article  PubMed  Google Scholar 

Nikolakopoulou A, Higgins JPT, Papakonstantinou T, Chaimani A, Del Giovane C, Egger M, et al. CINeMA: an approach for assessing confidence in the results of a network meta-analysis. PLoS Med. 2020;17(4):e1003082.

Article  PubMed  PubMed Central  Google Scholar 

Balduzzi S, Rücker G, Nikolakopoulou A, Papakonstantinou T, Salanti G, Efthimiou O, et al. Netmeta: an R package for network meta-analysis using frequentist methods. J Stat Softw. 2023;106(2):1–40.

Article  Google Scholar 

Guo J, Xiao M, Chu H, Lin L. Meta-analysis methods for risk difference: a comparison of different models. Stat Methods Med Res. 2023;32(1):3–21.

Article  PubMed  Google Scholar 

Murad MH, Wang Z, Zhu Y, Saadi S, Chu H, Lin L. Methods for deriving risk difference (absolute risk reduction) from a meta-analysis. BMJ. 2023;381:e073141.

Article  PubMed  Google Scholar 

Rosenberger KJ, Duan R, Chen Y, Lin L. Predictive P-score for treatment ranking in Bayesian network meta-analysis. BMC Med Res Methodol. 2021;21(1):213.

Article  PubMed  PubMed Central  Google Scholar 

Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21(11):1539–58.

Article  PubMed  Google Scholar 

Dias S, Welton NJ, Caldwell DM, Ades AE. Checking consistency in mixed treatment comparison meta-analysis. Stat Med. 2010;29(7–8):932–44.

Article  PubMed  CAS  Google Scholar 

Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315(7109):629–34.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Rucker G, Nikolakopoulou A, Papakonstantinou T, Salanti G, Riley RD, Schwarzer G. The statistical importance of a study for a network meta-analysis estimate. BMC Med Res Methodol. 2020;20(1):190.

Article  PubMed  PubMed Central  Google Scholar 

Papakonstantinou T, Nikolakopoulou A, Rucker G, Chaimani A, Schwarzer G, Egger M, et al. Estimating the contribution of studies in network meta-analysis: paths, flows and streams. F1000Res. 2018;7:610.

Article  PubMed  PubMed Central  Google Scholar 

Candelise L. Randomised controlled trial of streptokinase, aspirin, and combination of both in treatment of acute ischaemic stroke. Lancet. 1995;346(8989):1509–14.

Article  Google Scholar 

Hacke W, Kaste M, Fieschi C, Toni D, Lesaffre E, von Kummer R, et al. Intravenous thrombolysis with recombinant tissue plasminogen activator for acute hemispheric stroke. The European Cooperative Acute Stroke Study (ECASS). JAMA. 1995;274(13):1017–25.

Article  PubMed  CAS  Google Scholar 

Donnan GA, Davis SM, Chambers BR, Gates PC, Hankey GJ, McNeil JJ, et al. Streptokinase for acute ischemic stroke with relationship to time of administration: Australian Streptokinase (ASK) trial study group. JAMA. 1996;276(12):961–6.

Article  PubMed  CAS  Google Scholar 

Multicenter Acute Stroke Trial-Europe Study G, Hommel M, Cornu C, Boutitie F, Boissel JP. Thrombolytic therapy with streptokinase in acute ischemic stroke. N Engl J Med. 1996;335(3):145–50.

Article  Google Scholar 

Hacke W, Kaste M, Fieschi C, von Kummer R, Davalos A, Meier D, et al. Randomised double-blind placebo-controlled trial of thrombolytic therapy with intravenous alteplase in acute ischaemic stroke (ECASS II). Lancet. 1998;352(9136):1245–51.

Article  PubMed  CAS  Google Scholar 

Clark WM, Wissman S, Albers GW, Jhamandas JH, Madden KP, Hamilton S. Recombinant tissue-type plasminogen activator (Alteplase) for ischemic stroke 3 to 5 hours after symptom onset. The ATLANTIS study: a randomized controlled trial. Alteplase thrombolysis for acute noninterventional therapy in ischemic stroke. JAMA. 1999;282(21):2019–26.

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