Efficacy and Safety of Tenecteplase versus Alteplase in Acute Ischemic Stroke: A Systematic Review and Meta-Analysis
Iranian Journal of Child Neurology,
Vol. 20 No. 4 (2026),
1 September 2026
,
Page e2
https://doi.org/10.22037/ijcn.v20i4.46584
Abstract
Objectives:
The varying results of comparing different doses of tenecteplase (TNK) with alteplase (ALT) make it challenging to establish clear guidelines for managing acute ischemic stroke (AIS). This meta-analysis aims to compare the benefits and risks of tenecteplase 0.25 mg/kg versus ALT.
Materials & Methods:
This study is a comprehensive search of multiple databases to identify randomized controlled trials (RCTs) comparing the effects of TNK 0.25mg/kg and ALT in patients with AIS, until June 10, 2024. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Pooled analyses were performed using Stata V.17.
Results:
The present study analyzed eight trials involving 3647 patients with AIS who were treated with TNK and ALT. Compared to alteplase, tenecteplase (TNK 0.25 mg/kg) demonstrated a significant improvement in excellent recovery at three months (RR: 1.079, 95% CI 1.00–1.15). TNK exhibited non-inferiority to ALT regarding complete recanalization (RR: 1.47, 95% CI 0.87–2.50), combined complete/partial recanalization (RR: 1.20, 95% CI 0.86–1.68), early neurological improvement (RR: 1.04, 95% CI 0.83–1.29), and good recovery (RR: 1.02, 95% CI 0.90–1.15). While these findings trended in favor of TNK 0.25 mg/kg, the differences did not reach statistical significance. Furthermore, no significant differences were observed between TNK and ALT regarding poor recovery (RR: 0.87, 95% CI 0.67–1.13), parenchymal hematoma (RR: 0.78, 95% CI 0.21–2.81), intracerebral hemorrhage (ICH) (RR: 0.91, 95% CI 0.77–1.08), ICH symptoms (RR: 1.05, 95% CI 0.71–1.56), or 90-day mortality (RR: 1.00, 95% CI 0.83–1.19)
Conclusion:
Intravenous thrombolysis with TNK 0.25mg/kg in patients with AIS was shown to be as effective and safe as ALT, demonstrating non-inferiority. TNK showed significant superiority in terms of excellent recovery when compared to ALT. However, given the limitations of the present study, further RCTs with larger populations and more specific objectives are needed.
- Tenecteplase
- Alteplase
- Acute Ischemic stroke
- Thrombolysis
- Meta-analysis
How to Cite
References
Powers WJ. Acute ischemic stroke. New England Journal of Medicine. 2020;383(3):252-60.
Neumann-Haefelin T, Du Mesnil De Rochemont R, Fiebach J, Gass A, Nolte C, Kucinski T, et al. Effect of incomplete (spontaneous and postthrombolytic) recanalization after middle cerebral artery occlusion: a magnetic resonance imaging study. Stroke. 2004;35(1):109-14.
Bhatia R, Hill MD, Shobha N, Menon B, Bal S, Kochar P, et al. Low rates of acute recanalization with intravenous recombinant tissue plasminogen activator in ischemic stroke: real-world experience and a call for action. stroke. 2010;41(10):2254-8.
Whiteley WN, Emberson J, Lees KR, Blackwell L, Albers G, Bluhmki E, et al. Risk of intracerebral haemorrhage with alteplase after acute ischaemic stroke: a secondary analysis of an individual patient data meta-analysis. The Lancet Neurology. 2016;15(9):925-33.
Tanswell P, Modi N, Combs D, Danays T. Pharmacokinetics and pharmacodynamics of tenecteplase in fibrinolytic therapy of acute myocardial infarction. Clinical pharmacokinetics. 2002;41:1229-45.
Llevadot J, Giugliano RP, Antman EM. Bolus fibrinolytic therapy in acute myocardial infarction. Jama. 2001;286(4):442-9.
Nepal G, Kharel G, Ahamad ST, Basnet B. Tenecteplase versus alteplase for the management of acute ischemic stroke in a low-income country–Nepal: cost, efficacy, and safety. Cureus. 2018;10(2).
Campbell BC, Mitchell PJ, Churilov L, Yassi N, Kleinig TJ, Dowling RJ, et al. Tenecteplase versus alteplase before thrombectomy for ischemic stroke. New England Journal of Medicine. 2018;378(17):1573-82.
Haley Jr EC, Thompson JL, Grotta JC, Lyden PD, Hemmen TG, Brown DL, et al. Phase IIB/III trial of tenecteplase in acute ischemic stroke: results of a prematurely terminated randomized clinical trial. Stroke. 2010;41(4):707-11.
Huang X, Cheripelli BK, Lloyd SM, Kalladka D, Moreton FC, Siddiqui A, et al. Alteplase versus tenecteplase for thrombolysis after ischaemic stroke (ATTEST): a phase 2, randomised, open-label, blinded endpoint study. The Lancet Neurology. 2015;14(4):368-76.
Psychogios K, Palaiodimou L, Katsanos AH, Magoufis G, Safouris A, Kargiotis O, et al. Real-world comparative safety and efficacy of tenecteplase versus alteplase in acute ischemic stroke patients with large vessel occlusion. Therapeutic Advances in Neurological Disorders. 2021;14:1756286420986727.
Thommessen B, Næss H, Logallo N, Kvistad CE, Waje-Andreassen U, Ihle-Hansen H, et al. Tenecteplase versus alteplase after acute ischemic stroke at high age. International Journal of Stroke. 2021;16(3):295-9.
Logallo N, Novotny V, Assmus J, Kvistad CE, Alteheld L, Rønning OM, et al. Tenecteplase versus alteplase for management of acute ischaemic stroke (NOR-TEST): a phase 3, randomised, open-label, blinded endpoint trial. The Lancet Neurology. 2017;16(10):781-8.
Kvistad CE, Næss H, Helleberg BH, Idicula T, Hagberg G, Nordby LM, et al. 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. The Lancet Neurology. 2022;21(6):511-9.
Bivard A, Zhao H, Churilov L, Campbell BC, Coote S, Yassi N, et al. 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. The Lancet Neurology. 2022;21(6):520-7.
Parsons M, Spratt N, Bivard A, Campbell B, Chung K, Miteff F, et al. A randomized trial of tenecteplase versus alteplase for acute ischemic stroke. New England journal of medicine. 2012;366(12):1099-107.
Chen G, Bai C, Zhu Z, Li J, Shao S. Effectiveness and safety of different doses of tenecteplase in the treatment of acute ischemic stroke: A protocol for systematic review and meta-analysis. Medicine. 2021;100(3):e23805.
Potla N, Ganti L. Tenecteplase vs. alteplase for acute ischemic stroke: a systematic review. International journal of emergency medicine. 2022;15(1):1.
Moher D, Shamseer L, Clarke M, Ghersi D, Liberati A, Petticrew M, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Systematic reviews. 2015;4:1-9.
Demaerschalk BM, Kleindorfer DO, Adeoye OM, Demchuk AM, Fugate JE, Grotta JC, et al. Scientific rationale for the inclusion and exclusion criteria for intravenous alteplase in acute ischemic stroke: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2016;47(2):581-641.
Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, et al. 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. Stroke. 2019;50(12):e344-e418.
Berge E, Whiteley W, Audebert H, De Marchis GM, Fonseca AC, Padiglioni C, et al. European Stroke Organisation (ESO) guidelines on intravenous thrombolysis for acute ischaemic stroke. European stroke journal. 2021;6(1):I-LXII.
Seners P, Caroff J, Chausson N, Turc G, Denier C, Piotin M, et al. Recanalization before thrombectomy in tenecteplase vs. alteplase-treated drip-and-ship patients. Journal of Stroke. 2019;21(1):105.
Wei H, Fu B, Yang C, Huang M. The efficacy and safety of intravenous thrombolysis with tenecteplase versus alteplase for acute ischemic stroke: a systematic review and meta-analysis. Neurological Sciences. 2023;44(9):3005-15.
Kheiri B, Osman M, Abdalla A, Haykal T, Ahmed S, Hassan M, et al. Tenecteplase versus alteplase for management of acute ischemic stroke: a pairwise and network meta-analysis of randomized clinical trials. Journal of Thrombosis and Thrombolysis. 2018;46:440-50.
Zhang Y, Hou J, Wang L-Y. Therapeutic effect of tenecteplase on treatment of cerebral arterial thrombosis: a meta-analysis. European Review for Medical & Pharmacological Sciences. 2016;20(20).
Coutts SB, Dubuc V, Mandzia J, Kenney C, Demchuk AM, Smith EE, et al. Tenecteplase–tissue-type plasminogen activator evaluation for minor ischemic stroke with proven occlusion. Stroke. 2015;46(3):769-74.
Bivard A, Huang X, Levi CR, Spratt N, Campbell BC, Cheripelli BK, et al. Tenecteplase in ischemic stroke offers improved recanalization: analysis of 2 trials. Neurology. 2017;89(1):62-7.
Menon BK, Buck BH, Singh N, Deschaintre Y, Almekhlafi MA, Coutts SB, et al. Intravenous tenecteplase compared with alteplase for acute ischaemic stroke in Canada (AcT): a pragmatic, multicentre, open-label, registry-linked, randomised, controlled, non-inferiority trial. The Lancet. 2022;400(10347):161-9.
Salamatullah HK, Bashrahil B, Alghamdi AM, Alsharm FS, Alkulli OA, Alzahrani Z, et al. Efficacy and safety of tenecteplase in comparison to alteplase in acute ischemic stroke: A systematic review and meta-analysis of randomized controlled trials. Clinical Neurology and Neurosurgery. 2023:107961.
Huang X, MacIsaac R, Thompson JL, Levin B, Buchsbaum R, Haley Jr EC, et al. Tenecteplase versus alteplase in stroke thrombolysis: an individual patient data meta-analysis of randomized controlled trials. International Journal of Stroke. 2016;11(5):534-43.
Hu Y, Hou Y, Chen Z, Xiao Q, Chen H, Tao J, et al. Tenecteplase versus alteplase for acute ischemic stroke thrombolysis: a systematic review and meta-analysis. Neurology Asia. 2021;26(4).
Kobeissi H, Ghozy S, Turfe B, Bilgin C, Kadirvel R, Kallmes DF, et al. Tenecteplase vs. alteplase for treatment of acute ischemic stroke: a systematic review and meta-analysis of randomized trials. Frontiers in Neurology. 2023;14:1102463.
Rehman AU, Mohsin A, Cheema HA, Zahid A, Rehman MEU, Ameer MZ, et al. Comparative efficacy and safety of tenecteplase and alteplase in acute ischemic stroke: A pairwise and network meta-analysis of randomized controlled trials. Journal of the Neurological Sciences. 2023;445:120537.
Haley Jr EC, Lyden PD, Johnston KC, Hemmen TM, Investigators TiS. A pilot dose-escalation safety study of tenecteplase in acute ischemic stroke. Stroke. 2005;36(3):607-12.
Alamowitch S, Turc G, Palaiodimou L, Bivard A, Cameron A, De Marchis GM, et al. European Stroke Organisation (ESO) expedited recommendation on tenecteplase for acute ischaemic stroke. European Stroke Journal. 2023;8(1):8-54.
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