Hostname: page-component-54dcc4c588-mz6gc Total loading time: 0 Render date: 2025-09-27T18:51:05.561Z Has data issue: false hasContentIssue false
  • English
  • Français

Adjunctive Intraarterial Thrombolysis after Thrombectomy in Large Vessel Occlusion Stroke: A Meta-Analysis of RCTs

Published online by Cambridge University Press:  15 July 2025

Mohammed A. Almekhlafi ,
Hyungjong Park Open the ORCID record for Hyungjong Park [Opens in a new window] ,
Nishita Singh ,
Ronda Lun Open the ORCID record for Ronda Lun [Opens in a new window] ,
Umberto Pensato Open the ORCID record for Umberto Pensato [Opens in a new window] ,
Katrina Hannah Dizon Ignacio Open the ORCID record for Katrina Hannah Dizon Ignacio [Opens in a new window] ,
Johanna M. Ospel Open the ORCID record for Johanna M. Ospel [Opens in a new window] ,
Aravind Ganesh Open the ORCID record for Aravind Ganesh [Opens in a new window] ,
Mohamed Alshamrani  and
Andrew M. Demchuk
...Show all authors
Mohammed A. Almekhlafi
Affiliation:
Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada Department of Community Health Sciences and O’Brien Institute for Public Health, University of Calgary, Calgary, AB, Canada Department of Radiology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
Hyungjong Park*
Affiliation:
Department of Neurology, Keimyung University, School of Medicine, Daegu, South Korea.
Nishita Singh
Affiliation:
Department of Internal Medicine (Neurology Section), Rady Faculty of Medicine, University of Manitoba, Winnipeg, MB, Canada
Ronda Lun
Affiliation:
Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
Umberto Pensato
Affiliation:
Department of Neurology, IRCCS, Humanitas Research Hospital, Milan, Italy Department of Biomedical Sciences, Humanitas University, Milan, Italy
Katrina Hannah Dizon Ignacio
Affiliation:
Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada Department of Community Health Sciences and O’Brien Institute for Public Health, University of Calgary, Calgary, AB, Canada
Johanna M. Ospel
Affiliation:
Department of Radiology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
Aravind Ganesh
Affiliation:
Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada Department of Community Health Sciences and O’Brien Institute for Public Health, University of Calgary, Calgary, AB, Canada Department of Radiology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada Hotchkiss Brain Institute, Calgary, AB, Canada
Mohamed Alshamrani
Affiliation:
Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada Neuroscience Centre, King Faisal Specialist Hospital and Research Centre, Rydiah, Saudi Arabia
Andrew M. Demchuk
Affiliation:
Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada Department of Radiology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada Hotchkiss Brain Institute, Calgary, AB, Canada
Michael D. Hill
Affiliation:
Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada Department of Radiology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada Hotchkiss Brain Institute, Calgary, AB, Canada Department of Internal Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
Bijoy K. Menon
Affiliation:
Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada Department of Community Health Sciences and O’Brien Institute for Public Health, University of Calgary, Calgary, AB, Canada Department of Radiology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada Hotchkiss Brain Institute, Calgary, AB, Canada
*
Corresponding author: Hyungjong Park; Email: hjpark209042@gmail.com
Get access Rights & Permissions [Opens in a new window]

Abstract

Background and purpose:

Adjunctive intraarterial (IA) thrombolysis after endovascular thrombectomy may improve clinical outcomes in patients with large vessel occlusion (LVO) stroke possibly due to improvement in microvascular reperfusion.

Methods:

We conducted a meta-analysis of randomized controlled trials (RCTs) evaluating IA thrombolysis with tenecteplase, alteplase or urokinase in anterior or posterior circulation LVO stroke after successful reperfusion (modified Thrombolysis in Cerebral Infarction 2b–3). Efficacy outcomes were excellent functional outcome (modified Rankin Scale [mRS] 0–1), functional independence (mRS 0–2) and recovery without any disability (mRS 0) at 90 days. Safety outcomes included symptomatic intracerebral hemorrhage (ICH), any ICH and death. Odds ratios (OR) and 95% confidence intervals (CI) were pooled using random-effects models.

Results:

Seven RCTs (n = 2,130; 2022–2025) were included. IA thrombolytic drugs used were alteplase, tenecteplase and urokinase with doses ranging from 10 % to 50% of recommended IV dosage. IA thrombolysis significantly improved excellent functional outcome (mRS 0–1: OR 1.45, 95% CI 1.19–1.76) and recovery without any disability (mRS 0: OR 1.34, 95% CI 1.09–1.64), without safety risks (symptomatic ICH: 5.05% with IA thrombolytics vs. 4.49% in standard). Paradoxically, there was no difference in functional independence (mRS 0–2) (OR 1.09, 95% CI 0.99–1.20). Additionally, tenecteplase or alteplase at doses equivalent to 25% or 50% of recommended IV dosage significantly improved excellent functional outcome.

Conclusions:

IA thrombolysis offered immediately following EVT with successful reperfusion improved excellent functional outcome and recovery without disability at 90 days with an acceptable safety profile.

Résumé

RÉSUMÉ

Thrombolyse intra-artérielle adjuvante après une thrombectomie dans le cas d’un AVC avec occlusion des gros vaisseaux : une méta-analyse portant sur des essais contrôlés randomisés

Contexte et objectif :

La thrombolyse intra-artérielle adjuvante (TIAA) après la thrombectomie endovasculaire (TEV) peut améliorer l’évolution de l’état de santé clinique des patients victimes d’un AVC avec occlusion des gros vaisseaux, et ce, probablement en raison de l’amélioration de la reperfusion microvasculaire.

Méthodes :

Nous avons effectué une méta-analyse des essais contrôlés randomisés (ECR) évaluant la TIAA avec le tenécteplase, l’altéplase ou l’urokinase dans le cas d’un AVC avec occlusion des gros vaisseaux de la circulation antérieure ou postérieure après une reperfusion réussie (thrombolyse dans l’infarctus cérébral 2b-3 modifiée). Les critères d’efficacité étaient un excellent résultat fonctionnel (échelle de Rankin modifiée [ERM] : 0-1), l’autonomie fonctionnelle (ERM : 0-2) et la récupération sans aucune invalidité (ERM : 0) au bout de 90 jours. Les critères de sécurité comprenaient l’hémorragie intracérébrale (HIC) symptomatique, toute présence d’HIC et le décès. Les rapports de cotes (RC) et les intervalles de confiance (IC) à 95 % ont été regroupés à l’aide de modèles à effets aléatoires.

Résultats :

Au total, sept ECR (n = 2 130 de 2022 à 2025) ont été inclus. Les médicaments thrombolytiques intra-artériels utilisés étaient l’altéplase, la tenécteplase et l’urokinase, avec des doses allant de 10 à 50 % de la dose intra-artérielle recommandée. En définitive, la TIAA a amélioré de façon notable la fréquence d’excellents résultats fonctionnels (ERM : 0-1 ; RC : 1,45 ; IC 95 % : 1,19-1,76) et la récupération sans aucune invalidité (ERM : 0 ; RC : 1,34 ; IC 95 % : 1,09-1,64), et ce, sans risque pour la sécurité (HIC symptomatique : 5,05 % avec les médicaments thrombolytiques intra-artériels contre 4,49 % en ce qui regarde la norme). Paradoxalement, il n’y avait pas de différence en termes d’autonomie fonctionnelle (ERM : 0-2 ; RC : 1,09 ; IC 95 % : 0,99-1,20). De plus, le tenécteplase ou l’altéplase à des doses équivalentes à 25 % ou 50 % de la dose intra-artérielle recommandée ont significativement amélioré la fréquence d’excellents résultats fonctionnels.

Conclusions :

La TIAA proposée immédiatement après une TEV avec reperfusion réussie a amélioré la fréquence d’excellents résultats fonctionnels et la récupération sans invalidité au bout de 90 jours tout en maintenant un profil de sécurité acceptable.

Keywords

alteplaseendovascular thrombectomyintraarterial thrombolysistenecteplaseurokinase

Information

Type
Original Article
Information
Canadian Journal of Neurological Sciences , First View , pp. 1 - 9
Copyright
© The Author(s), 2025. Published by Cambridge University Press on behalf of Canadian Neurological Sciences Federation

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Article purchase

Temporarily unavailable

Footnotes

Mohammed A Almekhlafi and Hyungjong Park Contributed equally.

References

Dalkara, T, Arsava, EM. Can restoring incomplete microcirculatory reperfusion improve stroke outcome after thrombolysis? J Cereb Blood Flow Metab, 2012;32:2091–2099.Google Scholar
Rubiera, M, Garcia-Tornel, A, Olivé-Gadea, M, et al. Computed tomography perfusion after thrombectomy: an immediate surrogate marker of outcome after recanalization in acute stroke. Stroke. 2020;51:1736–1742.Google Scholar
Nie, X, Leng, X, Miao, Z, Fisher, M, Liu, L. Clinically ineffective reperfusion after endovascular therapy in acute ischemic stroke. Stroke. 2023;54:873–881.Google Scholar
Diprose, WK, Wang, MT, Ghate, K, et al. Adjunctive intra-arterial thrombolysis in endovascular thrombectomy: a systematic review and meta-analysis. Neurology. 2021;96:1135–1143.Google Scholar
Renú, A, Millán, M, San Román, L, et al. Effect of intra-arterial alteplase vs placebo following successful thrombectomy on functional outcomes in patients with large vessel occlusion acute ischemic stroke: the choice randomized clinical trial. JAMA. 2022;327:826–835.Google Scholar
Alhajala, H, Castonguay, A, Jumaa, M, et al. Adjunctive intra-arterial tenecteplase following mechanical thrombectomy. (ALLY) pilot trial. Stroke Vasc Interv Neurol. 2023;3:e12823_12027.Google Scholar
Liu, C, Guo, C, Li, F, et al. Intra-arterial urokinase after endovascular reperfusion for acute ischemic stroke: the POST-UK randomized clinical trial. JAMA. 2025;333:589.Google Scholar
Huang, J, Yang, J, Liu, C, et al. Intra-arterial tenecteplase following endovascular reperfusion for large vessel occlusion acute ischemic stroke: the POST-TNK randomized clinical trial. JAMA. 2025;333:579.Google Scholar
Hu, W, Tao, C, Wang, L, et al. Intra-arterial tenecteplase after successful endovascular recanalisation in patients with acute posterior circulation arterial occlusion (ATTENTION-IA): multicentre randomised controlled trial. BMJ. 2025;388:e080489.Google Scholar
Crocker, TF, Lam, N, Jordao, M, et al. Risk-of-bias assessment using Cochranes revised tool for randomized trials (RoB 2) was useful but challenging and resource-intensive: observations from a systematic review. J Clin Epidemiol. 2023;161:39–45.Google Scholar
Guyatt, GH, Oxman, AD, Vist, G, et al. GRADE guidelines: 4. Rating the quality of evidence—study limitations (risk of bias). J Clin Epidemiol. 2011;64:407–415.Google Scholar
IntHout, J, Ioannidis, JP, Borm, GF. The Hartung-Knapp-Sidik-Jonkman method for random effects meta-analysis is straightforward and considerably outperforms the standard DerSimonian-Laird method. BMC Med Res Methodol. 2014;14:1–12.Google Scholar
Van Den Noortgate, W, Onghena, P. Parametric and nonparametric bootstrap methods for meta-analysis. Behav Res Methods. 2005;37:11–22.Google Scholar
Hou, X, Huang, J, Wang, L, et al. Intra-arterial tenecteplase after successful reperfusion in large vessel occlusion stroke: A randomized clinical trial. JAMA Neurol. doi: 10.1001/jamaneurol.2025.2036. Google Scholar
ISC 2025 Session Report: Intra-Arterial Tenecteplase After Successful Recanalization Improves Neurological Outcomes. 2025.Google Scholar
Miao, Z, Luo, G, Song, L, et al. Intra-arterial tenecteplase for acute stroke after successful endovascular therapy. The ANGEL-TNK randomized clinical trial. JAMA. doi: 10.1001/jama.2025.10800.Google Scholar
Yang, X, He, X, Pan, D et al. Intra-arterial alteplase for acute ischaemic stroke after mechanical thrombectomy (PEARL): rationale and design of a multicentre, prospective, open-label, blinded-endpoint, randomised controlled trial. BMJ Open. 2024;14:e091059.Google Scholar
Hacke, W, Kaste, M, Bluhmki, E, et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ische mic stroke. N Engl J Med. 2008;359:1317–1329.Google Scholar
von Kummer, R, Broderick, JP, Campbell, BC, et al. The Heidelberg bleeding classification: classification of bleeding events after ischemic stroke and reperfusion therapy. Stroke. 2015;46:2981–2986.Google Scholar
Laredo, C, Rodríguez, A, Oleaga, L, et al. Adjunct thrombolysis enhances brain reperfusion following successful thrombectomy. Ann Neurol. 2022;92:860–870.Google Scholar
Powers, WJ, Rabinstein, AA, Ackerson, T, 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:e344–e418.Google Scholar
Hong, JM, Kim, DS, Kim, M. Hemorrhagic transformation a fter ischemic stroke: mechanisms and management. Front Neurol. 2021;12:703258.Google Scholar
Lorenzi, E, Crawford, AM, Anderson, CS, et al. Adaptive platform trials in stroke. Stroke. 2025;56:198–208.Google Scholar
Supplementary material: File

Almekhlafi et al. supplementary material

Almekhlafi et al. supplementary material
Download Almekhlafi et al. supplementary material(File)
File 10.5 MB