Intravenous Thrombolysis 4.5-9 Hours After Stroke Onset: A Cohort Study from the TRISP Collaboration

Valerian L Altersberger; Gerli Sibolt; Lukas S Enz; Christian Hametner; Jan F Scheitz; Hilde Henon; Guido Bigliardi; Davide Strambo; Nicolas Martinez-Majander; Lotte J Stolze; Mirjam R Heldner; Ilaria Grisendi; Dejana R Jovanovic; Yannick Bejot; Alessandro Pezzini; Ronen R Leker; Georg Kägi; Susanne Wegener; Carlo W Cereda; Georges Ntaios; Gian Marco De Marchis; Leo H Bonati; Marios Psychogios; Philippe Lyrer; Silja Räty; Marjaana Tiainen; Anke Wouters; François Caparros; Miriam Heyse; Hebun Erdur; Visnja Padjen; Marialuisa Zedde; Marcel Arnold; Paul J Nederkoorn; Patrik Michel; Andrea Zini; Charlotte Cordonnier; Christian H Nolte; Peter A Ringleb; Sami Curtze; Stefan T Engelter; Henrik Gensicke; TRISP collaborators

doi:10.1002/ana.26669

Intravenous Thrombolysis 4.5-9 Hours After Stroke Onset: A Cohort Study from the TRISP Collaboration

Ann Neurol. 2023 Aug;94(2):309-320. doi: 10.1002/ana.26669. Epub 2023 May 13.

Authors

Valerian L Altersberger¹, Gerli Sibolt², Lukas S Enz¹, Christian Hametner³, Jan F Scheitz⁴, Hilde Henon⁵, Guido Bigliardi⁶, Davide Strambo⁷, Nicolas Martinez-Majander², Lotte J Stolze⁸, Mirjam R Heldner⁹, Ilaria Grisendi¹⁰, Dejana R Jovanovic¹¹, Yannick Bejot¹², Alessandro Pezzini^{13

14}, Ronen R Leker¹⁵, Georg Kägi¹⁶, Susanne Wegener¹⁷, Carlo W Cereda¹⁸, Georges Ntaios¹⁹, Gian Marco De Marchis¹, Leo H Bonati¹, Marios Psychogios²⁰, Philippe Lyrer¹, Silja Räty², Marjaana Tiainen², Anke Wouters⁸, François Caparros⁵, Miriam Heyse³, Hebun Erdur⁴, Visnja Padjen¹¹, Marialuisa Zedde¹⁰, Marcel Arnold⁹, Paul J Nederkoorn⁸, Patrik Michel⁷, Andrea Zini²¹, Charlotte Cordonnier⁵, Christian H Nolte⁴, Peter A Ringleb³, Sami Curtze², Stefan T Engelter^{1

22}, Henrik Gensicke^{1

22}; TRISP collaborators

Affiliations

¹ Stroke Center and Department of Neurology, University Hospital Basel and University of Basel, Basel, Switzerland.
² Department of Neurology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
³ Department of Neurology, University Hospital Heidelberg, Heidelberg, Germany.
⁴ Department of Neurology with Experimental Neurology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Germany and Center for Stroke Research Berlin (CSB), Charité-Universitätsmedizin Berlin, Berlin, Germany.
⁵ Univ. Lille, Inserm, CHU Lille Lille Neuroscience & Cognition, Lille, France.
⁶ Stroke Unit, Department of Neuroscience, Ospedale Civile di Baggiovara, Modena University Hospital, Modena, Italy.
⁷ Stroke Center, Neurology Service, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
⁸ Department of Neurology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
⁹ Department of Neurology, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland.
¹⁰ Neurology Unit-Stroke Unit, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, Italy.
¹¹ Neurology Clinic, University Clinical Centre of Serbia, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
¹² Department of Neurology, University Hospital Dijon, Dijon, France.
¹³ Neurology Clinic, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
¹⁴ Department of Neurological Sciences and Vision, ASST Spedali Civili, Brescia, Italy.
¹⁵ Department of Neurology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
¹⁶ Department of Neurology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
¹⁷ Department of Neurology, University Hospital Zurich and University of Zurich, Zurich, Switzerland.
¹⁸ Stroke Center and Department of Neurology, Neurocenter of Southern Switzerland, Lugano, Switzerland.
¹⁹ Department of Internal Medicine, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece.
²⁰ Department of Neuroradiology, University Hospital Basel and University of Basel, Basel, Switzerland.
²¹ IRCCS Istituto delle Scienze Neurologiche di Bologna, Department of Neurology and Stroke Center, Maggiore Hospital, Bologna, Italy.
²² Neurology and Neurorehabilitation, University Department of Geriatric Medicine FELIX PLATTER, University of Basel, Basel, Switzerland.

PMID: 37114466
DOI: 10.1002/ana.26669

Abstract

Objective: To investigate the safety and effectiveness of intravenous thrombolysis (IVT) >4.5-9 hours after stroke onset, and the relevance of advanced neuroimaging for patient selection.

Methods: Prospective multicenter cohort study from the ThRombolysis in Ischemic Stroke Patients (TRISP) collaboration. Outcomes were symptomatic intracranial hemorrhage, poor 3-month functional outcome (modified Rankin scale 3-6) and mortality. We compared: (i) IVT >4.5-9 hours versus 0-4.5 hours after stroke onset and (ii) within the >4.5-9 hours group baseline advanced neuroimaging (computed tomography perfusion, magnetic resonance perfusion or magnetic resonance diffusion-weighted imaging fluid-attenuated inversion recovery) versus non-advanced neuroimaging.

Results: Of 15,827 patients, 663 (4.2%) received IVT >4.5-9 hours and 15,164 (95.8%) within 4.5 hours after stroke onset. The main baseline characteristics were evenly distributed between both groups. Time of stroke onset was known in 74.9% of patients treated between >4.5 and 9 hours. Using propensity score weighted binary logistic regression analysis (onset-to-treatment time >4.5-9 hours vs onset-to-treatment time 0-4.5 hours), the probability of symptomatic intracranial hemorrhage (OR_adjusted 0.80, 95% CI 0.53-1.17), poor functional outcome (OR_adjusted 1.01, 95% CI 0.83-1.22), and mortality (OR_adjusted 0.80, 95% CI 0.61-1.04) did not differ significantly between both groups. In patients treated between >4.5 and 9 hours, the use of advanced neuroimaging was associated with a 50% lower mortality compared with non-advanced imaging only (9.9% vs 19.7%; OR_adjusted 0.51, 95% CI 0.33-0.79).

Interpretation: This study showed no evidence in difference of symptomatic intracranial hemorrhage, poor outcome, and mortality in selected stroke patients treated with IVT between >4.5 and 9 hours after stroke onset compared with those treated within 4.5 hours. Advanced neuroimaging for patient selection was associated with lower mortality. ANN NEUROL 2023;94:309-320.

Publication types

Multicenter Study

MeSH terms

Brain Ischemia* / complications
Brain Ischemia* / diagnostic imaging
Brain Ischemia* / drug therapy
Cohort Studies
Fibrinolytic Agents / therapeutic use
Humans
Intracranial Hemorrhages / etiology
Ischemic Stroke* / complications
Prospective Studies
Stroke* / diagnostic imaging
Stroke* / drug therapy
Thrombolytic Therapy / methods
Treatment Outcome

Substances

Fibrinolytic Agents