Comparative Study

. 2024 Jul;55(7):1767-1775.

doi: 10.1161/STROKEAHA.124.046495. Epub 2024 May 15.

Outcomes of Bridging Intravenous Thrombolysis Versus Endovascular Therapy Alone in Late-Window Acute Ischemic Stroke

Jelle Demeestere^{1

2}, Muhammad M Qureshi^{3

4

5}, Lieselotte Vandewalle^{1

2}, Anke Wouters^{1

2}, Daniel Strbian^{6

7}, Raul G Nogueira^{8

9}, Simon Nagel^{10

11}, Hiroshi Yamagami¹², Volker Puetz^{13

14}, Mohamad Abdalkader^{3

5}, Diogo C Haussen⁹, Mahmoud H Mohammaden⁹, Markus A Möhlenbruch¹⁵, Marta Olivé-Gadea¹⁶, Simon Winzer^{13

14}, Marc Ribo¹⁶, Patrik Michel¹⁷, João Pedro Marto¹⁸, Kanta Tanaka¹⁹, Shinichi Yoshimura²⁰, Nicolas Martinez-Majander^{6

7}, Francois Caparros^{21

22}, Hilde Henon^{21

22}, Liisa Tomppo^{6

7}, Anne Dusart²³, Flavio Bellante²³, João Nuno Ramos²⁴, Jessica Jesser¹⁵, Sunil A Sheth²⁵, Santiago Ortega-Gutiérrez²⁶, James E Siegler²⁷, Stefania Nannoni²⁸, Johannes Kaesmacher²⁹, Tomas Dobrocky²⁹, Sergio Salazar-Marioni²⁵, Mudassir Farooqui²⁶, Pekka Virtanen^{30

7}, Rita Ventura¹⁸, Syed F Zaidi³¹, Alicia C Castonguay³¹, Kazutaka Uchida²⁰, Ajit S Puri³², Nobuyuki Sakai³³, Kazunori Toyoda¹⁹, Behzad Farzin³⁴, Hesham E Masoud³⁵, Piers Klein^{3

5}, Jenny Bui³, Federica Rizzo¹⁶, Daniel P O Kaiser^{14

36}, Philippe Desfontaines³⁷, Davide Strambo¹⁷, Charlotte Cordonnier^{21

22}, Eugene Lin³⁸, Peter A Ringleb¹¹, Daniel Roy³⁴, Osama O Zaidat³⁸, Urs Fischer³⁹, Jean Raymond³⁴, Robin Lemmens^{1

2}, Thanh N Nguyen^{3

5}

Affiliations

¹ Laboratory for Neurobiology, KU Leuven, Belgium (J.D., L.V., A.W., R.L.).
² Neurology, UZ Leuven, Belgium (J.D., L.V., A.W., R.L.).
³ Radiology (M.M.Q., M.A., P.K., J.B., T.N.N.), Boston Medical Center, MA.
⁴ Radiation Oncology (M.M.Q.), Boston Medical Center, MA.
⁵ Boston University Chobanian & Avedisian School of Medicine, MA (M.M.Q., M.A., P.K., T.N.N.).
⁶ Neurology (D.S., N.M.-M., L.T.), Helsinki University Hospital, Finland.
⁷ University of Helsinki, Finland (D.S., N.M.-M., L.T., P.V.).
⁸ Neurology, Neurosurgery, University of Pittsburgh Medical Center, MA (R.G.N.).
⁹ Neurology, Grady Memorial Hospital, Atlanta, GA (R.G.N., D.C.H., M.H.M.).
¹⁰ Neurology, Klinikum Ludwigshafen, Germany (S.N.).
¹¹ Neurology (S.N., P.A.R.), Heidelberg University Hospital, Germany.
¹² Stroke Neurology, NHO Osaka National Hospital, Japan (H.Y.).
¹³ Neurology (V.P., S.W.), Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany.
¹⁴ Dresden Neurovascular Center (V.P., S.W., D.P.O.K.), Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany.
¹⁵ Neuroradiology (M.A.M., J.J.), Heidelberg University Hospital, Germany.
¹⁶ Neurology, Hospital Vall d'Hebron, Barcelona, Spain (M.O.G., M.R., F.R.).
¹⁷ Neurology, Lausanne University Hospital and University of Lausanne, Switzerland (P.M., D.S.).
¹⁸ Neurology (J.P.M., R.V.), Hospital de Egas Moniz, Centro Hospitalar Lisboa Occidental, Lisbon, Portugal.
¹⁹ Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan (K. Tanaka, K. Toyoda).
²⁰ Neurosurgery, Hyogo Medical University, Nishinomiya, Japan (S.Y., K.U.).
²¹ Neurology, Centre Hospitalier Universitaire de Lille, France (F.C., H.H., C.C.).
²² Neurology, University of Lille, France (F.C., H.H., C.C.).
²³ Neurology, Hôpital Civil Marie Curie, Charleroi, Belgium (A.D., F.B.).
²⁴ Radiology (J.N.R.), Hospital de Egas Moniz, Centro Hospitalar Lisboa Occidental, Lisbon, Portugal.
²⁵ Neurology, UTHealth McGovern Medical School, Houston, TX (S.A.S., S.S.-M.).
²⁶ Neurology, University of Iowa, Iowa City (S.O.G., M.F.).
²⁷ Neurology, University of Chicago, IL (J.E.S.).
²⁸ Clinical Neurosciences, University of Cambridge, United Kingdom (S.N.).
²⁹ Diagnostic and Interventional Neuroradiology, University Hospital Bern, Switzerland (J.K., T.D.).
³⁰ Radiology (P.V.), Helsinki University Hospital, Finland.
³¹ Neurology, University of Toledo, OH (S.F.Z., A.C.C.).
³² Interventional Neuroradiology, University of Massachusetts Memorial Medical Center, Worcester (A.S.P.).
³³ Neurovascular Research, Kobe City Medical Center General Hospital, Japan (N.S.).
³⁴ Interventional Neuroradiology, Centre Hospitalier de l'Universite de Montreal, Canada (B.F., D.R., J.R.).
³⁵ Neurology, State University of New York, Syracuse (H.E.M.).
³⁶ Institute of Neuroradiology (D.P.O.K.), Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany.
³⁷ Neurology, CHC Liège, Belgium (P.D.).
³⁸ Neuroscience and Stroke Program, Bon Secours Mercy Health St. Vincent Hospital, Toledo, OH (E.L., O.O.Z.).
³⁹ Neurology, University Hospital Basel, Switzerland (U.F.).

PMID: 38748598
DOI: 10.1161/STROKEAHA.124.046495

Free article

Comparative Study

Outcomes of Bridging Intravenous Thrombolysis Versus Endovascular Therapy Alone in Late-Window Acute Ischemic Stroke

Jelle Demeestere et al. Stroke. 2024 Jul.

Free article

. 2024 Jul;55(7):1767-1775.

doi: 10.1161/STROKEAHA.124.046495. Epub 2024 May 15.

Authors

Affiliations

¹ Laboratory for Neurobiology, KU Leuven, Belgium (J.D., L.V., A.W., R.L.).
² Neurology, UZ Leuven, Belgium (J.D., L.V., A.W., R.L.).
³ Radiology (M.M.Q., M.A., P.K., J.B., T.N.N.), Boston Medical Center, MA.
⁴ Radiation Oncology (M.M.Q.), Boston Medical Center, MA.
⁵ Boston University Chobanian & Avedisian School of Medicine, MA (M.M.Q., M.A., P.K., T.N.N.).
⁶ Neurology (D.S., N.M.-M., L.T.), Helsinki University Hospital, Finland.
⁷ University of Helsinki, Finland (D.S., N.M.-M., L.T., P.V.).
⁸ Neurology, Neurosurgery, University of Pittsburgh Medical Center, MA (R.G.N.).
⁹ Neurology, Grady Memorial Hospital, Atlanta, GA (R.G.N., D.C.H., M.H.M.).
¹⁰ Neurology, Klinikum Ludwigshafen, Germany (S.N.).
¹¹ Neurology (S.N., P.A.R.), Heidelberg University Hospital, Germany.
¹² Stroke Neurology, NHO Osaka National Hospital, Japan (H.Y.).
¹³ Neurology (V.P., S.W.), Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany.
¹⁴ Dresden Neurovascular Center (V.P., S.W., D.P.O.K.), Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany.
¹⁵ Neuroradiology (M.A.M., J.J.), Heidelberg University Hospital, Germany.
¹⁶ Neurology, Hospital Vall d'Hebron, Barcelona, Spain (M.O.G., M.R., F.R.).
¹⁷ Neurology, Lausanne University Hospital and University of Lausanne, Switzerland (P.M., D.S.).
¹⁸ Neurology (J.P.M., R.V.), Hospital de Egas Moniz, Centro Hospitalar Lisboa Occidental, Lisbon, Portugal.
¹⁹ Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan (K. Tanaka, K. Toyoda).
²⁰ Neurosurgery, Hyogo Medical University, Nishinomiya, Japan (S.Y., K.U.).
²¹ Neurology, Centre Hospitalier Universitaire de Lille, France (F.C., H.H., C.C.).
²² Neurology, University of Lille, France (F.C., H.H., C.C.).
²³ Neurology, Hôpital Civil Marie Curie, Charleroi, Belgium (A.D., F.B.).
²⁴ Radiology (J.N.R.), Hospital de Egas Moniz, Centro Hospitalar Lisboa Occidental, Lisbon, Portugal.
²⁵ Neurology, UTHealth McGovern Medical School, Houston, TX (S.A.S., S.S.-M.).
²⁶ Neurology, University of Iowa, Iowa City (S.O.G., M.F.).
²⁷ Neurology, University of Chicago, IL (J.E.S.).
²⁸ Clinical Neurosciences, University of Cambridge, United Kingdom (S.N.).
²⁹ Diagnostic and Interventional Neuroradiology, University Hospital Bern, Switzerland (J.K., T.D.).
³⁰ Radiology (P.V.), Helsinki University Hospital, Finland.
³¹ Neurology, University of Toledo, OH (S.F.Z., A.C.C.).
³² Interventional Neuroradiology, University of Massachusetts Memorial Medical Center, Worcester (A.S.P.).
³³ Neurovascular Research, Kobe City Medical Center General Hospital, Japan (N.S.).
³⁴ Interventional Neuroradiology, Centre Hospitalier de l'Universite de Montreal, Canada (B.F., D.R., J.R.).
³⁵ Neurology, State University of New York, Syracuse (H.E.M.).
³⁶ Institute of Neuroradiology (D.P.O.K.), Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany.
³⁷ Neurology, CHC Liège, Belgium (P.D.).
³⁸ Neuroscience and Stroke Program, Bon Secours Mercy Health St. Vincent Hospital, Toledo, OH (E.L., O.O.Z.).
³⁹ Neurology, University Hospital Basel, Switzerland (U.F.).

PMID: 38748598
DOI: 10.1161/STROKEAHA.124.046495

Abstract

Background: Studies comparing bridging intravenous thrombolysis (IVT) with direct endovascular therapy (EVT) in patients with acute ischemic stroke who present late are limited. We aimed to compare the clinical outcomes and safety of bridging IVT in patients with acute ischemic stroke due to anterior circulation large vessel occlusion who underwent EVT 6 to 24 hours after time last known well.

Methods: We enrolled patients with anterior circulation large vessel occlusion stroke and a National Institutes of Health Stroke Scale score of ≥6 from 20 centers across 10 countries in the multicenter retrospective CLEAR study (CT for Late Endovascular Reperfusion) between January 2014 and May 2022. We used inverse probability of treatment weighting modeling adjusted for clinical and imaging confounders to compare functional outcomes, reperfusion success, symptomatic intracranial hemorrhage, and mortality between EVT patients with and without prior IVT.

Results: Of 5098 patients screened for eligibility, we included 2749 patients, of whom 549 received bridging IVT before EVT. The timing of IVT was not recorded. Witnessed stroke onset and transfer rates were higher in the bridging IVT group (25% versus 12% and 77% versus 55%, respectively, P value for both <0.0001), and time intervals between stroke onset and treatment were shorter (time last known well-start of EVT median 560 minutes [interquartile range, 432-791] versus 724 minutes [interquartile range, 544-912]; P<0.0001). After adjustment for confounders, there was no difference in functional outcome at 3 months (adjusted common odds ratio for modified Rankin Scale shift, 1.03 [95% CI, 0.89-1.19]; P=0.72) or successful reperfusion (adjusted odds ratio, 1.19 [95% CI, 0.81-1.75]; P=0.39). There were no safety concerns associated with bridging IVT versus direct EVT (symptomatic intracranial hemorrhage: adjusted odds ratio, 0.75 [95% CI, 0.38-1.48]; P=0.40; mortality: adjusted odds ratio, 1.14 [95% CI, 0.89-1.46]; P=0.31). Results were unchanged when the analysis was limited to patients who received IVT >6 hours after last known well.

Conclusions: In patients with an anterior circulation large vessel occlusion stroke who underwent EVT 6 to 24 hours from last known well, bridging IVT was not associated with a difference in outcomes compared with direct EVT.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04096248.

Keywords: endovascular procedures; ischemic stroke; reperfusion; stroke; thrombolytic therapy.

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Conflict of interest statement

Disclosures Drs Demeestere and Lemmens reported institutional research fees from Genentech. Dr Strbian reported consultancy fees from AstraZeneca and Boehringer Ingelheim. Dr Nogueira reported consultancy for Biogen, Brainomix, Corindus, Cerenovus, Stryker, Medtronic, Ceretrieve, Anaconda, Biomed, Vesalio, Imperative Care, NeuroVasc Technologies, Viz AI, Genentech, Prolong Pharmaceuticals, Perfuze, Phenox, RapidPulse; stock options in Viz AI, Vesalio, Perfuze, Corindus, Brainomix, Ceretrieve; grants from Cerenovus and Stryker. Dr Nagel reported consultancy for Brainomix; speaker with Boehringer ingelheim and Pfizer. Dr Yamagami reported research grants from Bristol Myers Squibb; lecturer’s fees from Stryker, Medtronic, Johnson & Johnson, Bayer, Daiichi Sankyo, Bristol Myers Squibb, Otuska Pharmaceutical; advisory board for Daiichi Sankyo. Dr Puetz reported lecturer for Daiichi Sankyo. Dr Haussen reported consultancy for Vesalio, Cerenovus, Stryker, Brainomix, Poseydon Medical, and Chiesi USA; Data Safety and Monitoring Board from Jacobs Institute; and stock options in Viz AI. Dr Ribo reported consultancy for Medtronic, MiniMed, Cerenovus, AptaTargets, Stryker, Philips; stock holdings in Methinks, Nora, and Anaconda Biomed. Dr Michel reported grants from University of Lausanne and Swiss National Science Foundation (SNF). Dr Marto reported consulting from Amicus Therapeutics, Boehringer Ingelheim; Speaker with Boehringer Ingelheim. Dr Henon reported fees from Novartis and a grant from Sanofi-Aventis. Dr Gutierrez reported consultancy fees from Medtronic, Stryker and Microvention, and a grant from Methinks, Microvention, Stryker and the National Institutes of Health. Dr Siegler reported a grant from Philips and Viz AI. Dr Yoshimura reported research grants from Stryker, Siemens Healthineers, Bristol Myers Squibb, Sanofi, Eisai, Daiichi Sankyo, Teijin Pharma, Chugai Pharmaceutical, HEALIOS, Asahi Kasei Medical, Kowa, CSL Behring; lecturer fees from Stryker, Medtronic, Johnson & Johnson, Kaneka, Terumo, Biomedical Solutions, Boehringer Ingelheim, Daiichi Sankyo, Bayer and Bristol-Meyers Squibb. Dr Sheth reported consultancy for Imperative Care, Viz AI, Penumbra; compensation from Motif Neurosciences; grants from National Institutes of Health. Dr Dobrocky reported consultancy fees from MicroVention. Dr Kaesmacher reported grants from the Swiss Academy of Medical Sciences/Bangerter Foundation, Swiss Stroke Society, and Clinical Trials Unit Bern. Dr Zaidi reported a grant from Genentech. Dr Castonguay reported employment by Medtronic. Dr Uchida reported fees by Bristol Myers Squibb, Daiichi Sankyo, Medtronic and Stryker. Dr Sakai reported research grant from Biomedical Solutions, Medtronic, Terumo, TG Medical; lecturer’s fees from Asahi-Intec, Biomedical Solutions, Daiichi Sankyo, Kaneka, Medtronic, Terumo; advisory board for Johnson & Johnson, Medtronic, Terumo. Dr Toyoda reported lecturer fees from Otsuka, Daiichi Sankyo, Bayer, Novartis, and Bristol-Myers Squibb. Dr Kaiser reported grants from the Joachim Herz Foundation. Dr Möhlenbruch reported grants from Medtronic, Stryker, and MicroVention. Dr Ringleb reported travel support from Bayer and Bristol Myers Squibb; consultancy for Daiichi Sankyo Company and Boehringer Ingelheim. Dr Zaidat reported consultancy fees by Johnson & Johnson, Medtronic and Stryker, Penumbra stock, and a grant from Johson & Johnson, Medtronic, Penumbra and Stryker. Dr Fischer reported research support from SNF, Medtronic, Stryker, Rapid Medical, Penumbra, Phenox; consultancies for Stryker, CSL Behring; advisory board for Alexion/Portola, Boehringer Ingelheim, Biogen, Acthera. Dr Nguyen discloses research support from Medtronic to her institution; advisory board for Brainomix, Aruna Bio; Associate Editor Stroke.

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Outcomes of Bridging Intravenous Thrombolysis Versus Endovascular Therapy Alone in Late-Window Acute Ischemic Stroke

Affiliations

Outcomes of Bridging Intravenous Thrombolysis Versus Endovascular Therapy Alone in Late-Window Acute Ischemic Stroke

Authors

Affiliations

Abstract

Conflict of interest statement

References

Publication types

MeSH terms

Substances

Associated data

LinkOut - more resources

Full Text Sources

Medical