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Intravenous thrombolysis for ischemic stroke in extended time window selected with CT perfusion: a systematic review and meta-analysis.

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Title: Intravenous thrombolysis for ischemic stroke in extended time window selected with CT perfusion: a systematic review and meta-analysis.
Authors: Naccarato M; Neurology Unit, Department of Medicine, Surgery and Health Sciences, University Hospital and Health Services of Trieste, University of Trieste, Italy. Electronic address: marcello.naccarato@asugi.sanita.fvg.it., Ricci E; Neurology Unit, Department of Medicine, Surgery and Health Sciences, University Hospital and Health Services of Trieste, University of Trieste, Italy., Vincis E; Neurology Unit, Department of Medicine, Surgery and Health Sciences, University Hospital and Health Services of Trieste, University of Trieste, Italy., Quagliotto M; Neurology Unit, Department of Medicine, Surgery and Health Sciences, University Hospital and Health Services of Trieste, University of Trieste, Italy., Malesani M; Neurology Unit, Department of Medicine, Surgery and Health Sciences, University Hospital and Health Services of Trieste, University of Trieste, Italy., Farina G; Neurology Unit, Department of Medicine, Surgery and Health Sciences, University Hospital and Health Services of Trieste, University of Trieste, Italy., Maurig SE; Neurology Unit, Department of Medicine, Surgery and Health Sciences, University Hospital and Health Services of Trieste, University of Trieste, Italy., Caruso P; Neurology Unit, Department of Medicine, Surgery and Health Sciences, University Hospital and Health Services of Trieste, University of Trieste, Italy., Furlanis G; Neurology Unit, Department of Medicine, Surgery and Health Sciences, University Hospital and Health Services of Trieste, University of Trieste, Italy., Manganotti P; Neurology Unit, Department of Medicine, Surgery and Health Sciences, University Hospital and Health Services of Trieste, University of Trieste, Italy.
Source: Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association [J Stroke Cerebrovasc Dis] 2026 Sep; Vol. 35 (9), pp. 108717. Date of Electronic Publication: 2026 Jul 31.
Publication Type: Journal Article; Systematic Review; Meta-Analysis
Language: English
Journal Info: Publisher: Saunders Country of Publication: United States NLM ID: 9111633 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1532-8511 (Electronic) Linking ISSN: 10523057 NLM ISO Abbreviation: J Stroke Cerebrovasc Dis Subsets: MEDLINE
Imprint Name(s): Publication: Philadelphia, PA : Saunders
Original Publication: New York, NY : Demos Publications, [1991-
MeSH Terms: Cerebrovascular Circulation*/drug effects , Fibrinolytic Agents*/administration & dosage , Fibrinolytic Agents*/adverse effects , Ischemic Stroke*/drug therapy , Ischemic Stroke*/diagnostic imaging , Ischemic Stroke*/physiopathology , Ischemic Stroke*/mortality , Perfusion Imaging*/methods , Thrombolytic Therapy*/adverse effects , Thrombolytic Therapy*/mortality , Thrombolytic Therapy*/methods , Time-to-Treatment* , Tomography, X-Ray Computed*, Aged ; Female ; Humans ; Male ; Middle Aged ; Administration, Intravenous ; Functional Status ; Predictive Value of Tests ; Randomized Controlled Trials as Topic ; Recovery of Function ; Risk Factors ; Time Factors ; Treatment Outcome
Abstract: Purpose: Recent randomized controlled trials (RCTs) have provided new evidence regarding the efficacy and safety of intravenous thrombolysis (IVT) in patients with acute ischemic stroke (AIS) presenting within the extended time window (ETW). We performed a systematic review and meta-analysis to evaluate the efficacy and safety of IVT, in patients treated within the ETW and selected with perfusion imaging criteria, predominantly computed tomography perfusion (CTP).
Methods: A systematic review and meta-analysis, registered in PROSPERO, was conducted including all available RCTs comparing IVT with best medical treatment (BMT) in patients with AIS within the ETW, selected using advanced perfusion imaging criteria. The predefined efficacy outcomes were excellent functional outcome and good functional outcome at 3 months. The safety endpoints included symptomatic intracranial hemorrhage (sICH) and all-cause mortality at 90 days.
Results: Six RCTs, including 1182 patients treated with IVT and 1176 patients receiving BMT, were included. IVT was associated with a higher likelihood of achieving excellent and good functional outcomes at 3 months. Exploratory subgroup analyses by treatment timing suggested consistent findings up to 24 hours. No significant difference in 90-day mortality was observed between groups, whereas IVT was associated with an increased risk of sICH.
Conclusion: Treatment with IVT in the ETW (4.5-24 h) in patients selected using advanced perfusion imaging, predominantly CTP, may be associated with improved functional outcomes in patients with AIS. Although IVT was associated with an increased risk of sICH, no significant increase in 90-day mortality was observed.
Prospero Registration: CRD420261304314.
(Copyright © 2026 The Authors. Published by Elsevier Inc. All rights reserved.)
Competing Interests: Declaration of competing interest The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Contributed Indexing: Keywords: Acute ischemic stroke; CTP; Extended time window; Meta-analysis; Perfusion imaging; Thrombolysis
Substance Nomenclature: 0 (Fibrinolytic Agents)
Entry Date(s): Date Created: 20260731 Date Completed: 20260820 Latest Revision: 20260901
Update Code: 20260901
DOI: 10.1016/j.jstrokecerebrovasdis.2026.108717
PMID: 42537729
Database: MEDLINE
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  Data: Intravenous thrombolysis for ischemic stroke in extended time window selected with CT perfusion: a systematic review and meta-analysis.
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  Data: <searchLink fieldCode="AU" term="%22Naccarato+M%22">Naccarato M</searchLink>; Neurology Unit, Department of Medicine, Surgery and Health Sciences, University Hospital and Health Services of Trieste, University of Trieste, Italy. Electronic address: marcello.naccarato@asugi.sanita.fvg.it.<br /><searchLink fieldCode="AU" term="%22Ricci+E%22">Ricci E</searchLink>; Neurology Unit, Department of Medicine, Surgery and Health Sciences, University Hospital and Health Services of Trieste, University of Trieste, Italy.<br /><searchLink fieldCode="AU" term="%22Vincis+E%22">Vincis E</searchLink>; Neurology Unit, Department of Medicine, Surgery and Health Sciences, University Hospital and Health Services of Trieste, University of Trieste, Italy.<br /><searchLink fieldCode="AU" term="%22Quagliotto+M%22">Quagliotto M</searchLink>; Neurology Unit, Department of Medicine, Surgery and Health Sciences, University Hospital and Health Services of Trieste, University of Trieste, Italy.<br /><searchLink fieldCode="AU" term="%22Malesani+M%22">Malesani M</searchLink>; Neurology Unit, Department of Medicine, Surgery and Health Sciences, University Hospital and Health Services of Trieste, University of Trieste, Italy.<br /><searchLink fieldCode="AU" term="%22Farina+G%22">Farina G</searchLink>; Neurology Unit, Department of Medicine, Surgery and Health Sciences, University Hospital and Health Services of Trieste, University of Trieste, Italy.<br /><searchLink fieldCode="AU" term="%22Maurig+SE%22">Maurig SE</searchLink>; Neurology Unit, Department of Medicine, Surgery and Health Sciences, University Hospital and Health Services of Trieste, University of Trieste, Italy.<br /><searchLink fieldCode="AU" term="%22Caruso+P%22">Caruso P</searchLink>; Neurology Unit, Department of Medicine, Surgery and Health Sciences, University Hospital and Health Services of Trieste, University of Trieste, Italy.<br /><searchLink fieldCode="AU" term="%22Furlanis+G%22">Furlanis G</searchLink>; Neurology Unit, Department of Medicine, Surgery and Health Sciences, University Hospital and Health Services of Trieste, University of Trieste, Italy.<br /><searchLink fieldCode="AU" term="%22Manganotti+P%22">Manganotti P</searchLink>; Neurology Unit, Department of Medicine, Surgery and Health Sciences, University Hospital and Health Services of Trieste, University of Trieste, Italy.
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  Data: <searchLink fieldCode="JN" term="%229111633%22">Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association</searchLink> [J Stroke Cerebrovasc Dis] 2026 Sep; Vol. 35 (9), pp. 108717. <i>Date of Electronic Publication: </i>2026 Jul 31.
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  Data: <i>Publisher: </i><searchLink fieldCode="PB" term="%22Saunders%22">Saunders </searchLink><i>Country of Publication: </i>United States <i>NLM ID: </i>9111633 <i>Publication Model: </i>Print-Electronic <i>Cited Medium: </i>Internet <i>ISSN: </i>1532-8511 (Electronic) <i>Linking ISSN: </i><searchLink fieldCode="IS" term="%2210523057%22">10523057 </searchLink><i>NLM ISO Abbreviation: </i>J Stroke Cerebrovasc Dis <i>Subsets: </i>MEDLINE
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  Data: <i>Publication</i>: Philadelphia, PA : Saunders<br /><i>Original Publication</i>: New York, NY : Demos Publications, [1991-
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– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Purpose: Recent randomized controlled trials (RCTs) have provided new evidence regarding the efficacy and safety of intravenous thrombolysis (IVT) in patients with acute ischemic stroke (AIS) presenting within the extended time window (ETW). We performed a systematic review and meta-analysis to evaluate the efficacy and safety of IVT, in patients treated within the ETW and selected with perfusion imaging criteria, predominantly computed tomography perfusion (CTP).<br />Methods: A systematic review and meta-analysis, registered in PROSPERO, was conducted including all available RCTs comparing IVT with best medical treatment (BMT) in patients with AIS within the ETW, selected using advanced perfusion imaging criteria. The predefined efficacy outcomes were excellent functional outcome and good functional outcome at 3 months. The safety endpoints included symptomatic intracranial hemorrhage (sICH) and all-cause mortality at 90 days.<br />Results: Six RCTs, including 1182 patients treated with IVT and 1176 patients receiving BMT, were included. IVT was associated with a higher likelihood of achieving excellent and good functional outcomes at 3 months. Exploratory subgroup analyses by treatment timing suggested consistent findings up to 24 hours. No significant difference in 90-day mortality was observed between groups, whereas IVT was associated with an increased risk of sICH.<br />Conclusion: Treatment with IVT in the ETW (4.5-24 h) in patients selected using advanced perfusion imaging, predominantly CTP, may be associated with improved functional outcomes in patients with AIS. Although IVT was associated with an increased risk of sICH, no significant increase in 90-day mortality was observed.<br />Prospero Registration: CRD420261304314.<br /> (Copyright © 2026 The Authors. Published by Elsevier Inc. All rights reserved.)
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  Data: Declaration of competing interest The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
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  Data: <i>Keywords: </i>Acute ischemic stroke; CTP; Extended time window; Meta-analysis; Perfusion imaging; Thrombolysis
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