Tenecteplase Vs. Alteplase for Treatment of Acute Ischemic Stroke: A Systematic Review and Meta-analysis of Randomized Trials

Overview

Journal Front Neurol

Specialty Neurology

Date 2023 Feb 9

PMID 36756249

Authors

Hassan Kobeissi

Sherief Ghozy

Bilal Turfe

Cem Bilgin

Ramanathan Kadirvel

David F Kallmes

Waleed Brinjikji

Alejandro A Rabinstein

Affiliations

Soon will be listed here.

Abstract

Background And Objectives: Several randomized controlled trials (RCTs) have compared tenecteplase to alteplase for treatment of acute ischemic stroke (AIS). Yet, there is no meta-analysis that includes the latest published RCTs of 2022. We sought to compare the safety and efficacy of tenecteplase vs. alteplase for the treatment of AIS through a meta-analysis of all published RCTs.

Methods: A systematic literature review of the English language literature was conducted using PubMed, Web of Science, Scopus, and Embase. We included RCTs that focused on patients with AIS treated with tenecteplase and alteplase. Multiple reviewers screened through potential studies to identify the final papers included in our analysis. Following PRISMA guidelines, multiple authors extracted data to ensure accuracy. Data were pooled using a random-effects model.

Results: Nine trials, with 3,706 patients, compared outcomes of patients treated with tenecteplase and alteplase for AIS. Both treatments resulted in comparable rates of modified Rankin Scale (mRS) 0-1 at 90 days (RR = 1.03; 95% CI = 0.97-1.10; -value = 0.359) and mRS 0-2 at 90 days (RR = 1.03; 95% CI = 0.87-1.22; -value = 0.749). There was no heterogeneity among included studies regarding mRS 0-1 rates (I = 26%; -value = 0.211); however, there was significant heterogeneity in mRS 0-2 rates (I = 71%; -value = 0.002). Similarly, rates of mortality (RR = 0.97; 95% CI = 0.81-1.16; -value = 0.746) and symptomatic intracranial hemorrhage (sICH) rates (RR = 1.10; 95% CI = 0.75-1.61; -value = 0.622) were comparable in both treatment groups. There was no significant heterogeneity among included studies in either mortality (I = 30%; -value = 0.181) or sICH (I = 0%; -value = 0.734) rates. Further analysis comparing dosing of tenecteplase (0.1, 0.25, 0.32, and 0.4 mg/kg) yielded no significant differences for any of the endpoints (mRS 0-1, mRS 0-2, sICH, and mortality) compared to alteplase.

Discussion: Based on available evidence from completed RCTs, tenecteplase has proven similar safety and efficacy to alteplase for treatment of AIS.

Citing Articles

Emergency Department Workflow Times of Intravenous Thrombolysis with Tenecteplase versus Alteplase in Acute Ischemic Stroke: A Prospective Cohort Study before and during the COVID-19 Pandemic.

Guzman M, Lavados P, Cavada G, Brunser A, Olavarria V Cerebrovasc Dis Extra. 2025; 15(1):102-109.

PMID: 39899997 PMC: 11882161. DOI: 10.1159/000543900.

Thrombolytic therapy for patients with acute ischemic stroke: systematic review and network meta-analysis of randomized trials.

Sun L, Li W, Chen W, Ren Z, Li C, Jiang Z Front Neurol. 2025; 15():1490476.

PMID: 39839875 PMC: 11746078. DOI: 10.3389/fneur.2024.1490476.

Anti-Inflammatory Thrombolytic JX10 (TMS-007) in Late Presentation of Acute Ischemic Stroke.

Niizuma K, Nishimura N, Hasegawa K, Moritoyo T, Kudo K, Bell J Stroke. 2024; 55(12):2786-2794.

PMID: 39508107 PMC: 11593998. DOI: 10.1161/STROKEAHA.124.048464.

Rapid recommendations: Updates from 2023 guidelines: part 1.

OToole D Can Fam Physician. 2024; 70(9):555-557.

PMID: 39271218 PMC: 11407600. DOI: 10.46747/cfp.7009555.

[Thrombolysis alert in ischemic stroke: experience of the international private clinic Al Badie in Fez (cross-sectional study of 60 cases)].

Najmi I, Idrissi S, Bensouda K, Marzouki Z, Dinia M, Talbi I Pan Afr Med J. 2024; 47:167.

PMID: 39036032 PMC: 11260060. DOI: 10.11604/pamj.2024.47.167.42376.

References

Ibanez B, James S, Agewall S, Antunes M, Bucciarelli-Ducci C, Bueno H . 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: The Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European.... Eur Heart J. 2017; 39(2):119-177. DOI: 10.1093/eurheartj/ehx393. View

Liberati A, Altman D, Tetzlaff J, Mulrow C, Gotzsche P, Ioannidis J . The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. PLoS Med. 2009; 6(7):e1000100. PMC: 2707010. DOI: 10.1371/journal.pmed.1000100. View

Bhaumik D, Amatya A, Normand S, Greenhouse J, Kaizar E, Neelon B . Meta-Analysis of Rare Binary Adverse Event Data. J Am Stat Assoc. 2013; 107(498):555-567. PMC: 3665366. DOI: 10.1080/01621459.2012.664484. View

Tanswell P, Modi N, Combs D, Danays T . Pharmacokinetics and pharmacodynamics of tenecteplase in fibrinolytic therapy of acute myocardial infarction. Clin Pharmacokinet. 2002; 41(15):1229-45. DOI: 10.2165/00003088-200241150-00001. View

Burns P, Rohrich R, Chung K . The levels of evidence and their role in evidence-based medicine. Plast Reconstr Surg. 2011; 128(1):305-310. PMC: 3124652. DOI: 10.1097/PRS.0b013e318219c171. View

Kvistad C, Naess H, Helleberg B, Idicula T, Hagberg G, Nordby L . 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. Lancet Neurol. 2022; 21(6):511-519. DOI: 10.1016/S1474-4422(22)00124-7. View

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. PMC: 2127453. DOI: 10.1136/bmj.315.7109.629. View

Parsons M, Spratt N, Bivard A, Campbell B, Chung K, Miteff F . A randomized trial of tenecteplase versus alteplase for acute ischemic stroke. N Engl J Med. 2012; 366(12):1099-107. DOI: 10.1056/NEJMoa1109842. View

Sterne J, Savovic J, Page M, Elbers R, Blencowe N, Boutron I . RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019; 366:l4898. DOI: 10.1136/bmj.l4898. View

10.

Huang X, Cheripelli B, Lloyd S, Kalladka D, Moreton F, Siddiqui A . Alteplase versus tenecteplase for thrombolysis after ischaemic stroke (ATTEST): a phase 2, randomised, open-label, blinded endpoint study. Lancet Neurol. 2015; 14(4):368-76. DOI: 10.1016/S1474-4422(15)70017-7. View

11.

Menon B, Buck B, Singh N, Deschaintre Y, Almekhlafi M, Coutts S . Intravenous tenecteplase compared with alteplase for acute ischaemic stroke in Canada (AcT): a pragmatic, multicentre, open-label, registry-linked, randomised, controlled, non-inferiority trial. Lancet. 2022; 400(10347):161-169. DOI: 10.1016/S0140-6736(22)01054-6. View

12.

Rucker G, Schwarzer G . Ranking treatments in frequentist network meta-analysis works without resampling methods. BMC Med Res Methodol. 2015; 15:58. PMC: 4521472. DOI: 10.1186/s12874-015-0060-8. View

13.

Salanti G, Del Giovane C, Chaimani A, Caldwell D, Higgins J . Evaluating the quality of evidence from a network meta-analysis. PLoS One. 2014; 9(7):e99682. PMC: 4084629. DOI: 10.1371/journal.pone.0099682. View

14.

Haldane J . The estimation and significance of the logarithm of a ratio of frequencies. Ann Hum Genet. 1956; 20(4):309-11. DOI: 10.1111/j.1469-1809.1955.tb01285.x. View

15.

Begg C, Mazumdar M . Operating characteristics of a rank correlation test for publication bias. Biometrics. 1994; 50(4):1088-101. View

16.

Bivard A, Zhao H, Churilov L, Campbell B, Coote S, Yassi N . 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. Lancet Neurol. 2022; 21(6):520-527. DOI: 10.1016/S1474-4422(22)00171-5. View

17.

Campbell B, Mitchell P, Churilov L, Yassi N, Kleinig T, Dowling R . Tenecteplase versus Alteplase before Thrombectomy for Ischemic Stroke. N Engl J Med. 2018; 378(17):1573-1582. DOI: 10.1056/NEJMoa1716405. View

18.

Campbell B, Mitchell P, Churilov L, Yassi N, Kleinig T, Dowling R . Effect of Intravenous Tenecteplase Dose on Cerebral Reperfusion Before Thrombectomy in Patients With Large Vessel Occlusion Ischemic Stroke: The EXTEND-IA TNK Part 2 Randomized Clinical Trial. JAMA. 2020; 323(13):1257-1265. PMC: 7139271. DOI: 10.1001/jama.2020.1511. View

19.

Haley Jr E, Thompson J, Grotta J, Lyden P, Hemmen T, Brown D . Phase IIB/III trial of tenecteplase in acute ischemic stroke: results of a prematurely terminated randomized clinical trial. Stroke. 2010; 41(4):707-11. PMC: 2860601. DOI: 10.1161/STROKEAHA.109.572040. View

20.

Logallo N, Novotny V, Assmus J, Kvistad C, Alteheld L, Ronning O . Tenecteplase versus alteplase for management of acute ischaemic stroke (NOR-TEST): a phase 3, randomised, open-label, blinded endpoint trial. Lancet Neurol. 2017; 16(10):781-788. DOI: 10.1016/S1474-4422(17)30253-3. View