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  • Interaction between intravenous thrombolysis and clinical outcome between slow and fast progressors undergoing mechanical thrombectomy: a post-hoc analysis of the SWIFT-DIRECT trial

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Ischemic stroke
Original research
Interaction between intravenous thrombolysis and clinical outcome between slow and fast progressors undergoing mechanical thrombectomy: a post-hoc analysis of the SWIFT-DIRECT trial
  1. Gaultier Marnat1,
  2. Johannes Kaesmacher2,
  3. Lukas Buetikofer3,
  4. Igor Sibon4,
  5. Suzana Saleme5,
  6. Raoul Pop6,
  7. Hilde Henon7,
  8. Patrik Michel8,
  9. Mikaël Mazighi9,10,
  10. Zsolt Kulcsar11,
  11. Kevin Janot12,
  12. Paolo Machi13,
  13. Aleksandra Pikula14,
  14. Jean-Christophe Gentric15,
  15. María Hernández-Pérez16,
  16. Lars Udo Krause17,
  17. Guillaume Turc18,19,20,21,
  18. David S Liebeskind22,
  19. Jan Gralla23,
  20. Urs Fischer24
  21. on behalf of the SWIFT-DIRECT investigators
    1. 1 Interventional and Diagnostic Neuroradiology, University Hospital Centre Bordeaux, Bordeaux, Aquitaine, France
    2. 2 Neuroradiology, University Hospital Bern, Bern, Switzerland
    3. 3 CTU Bern, University of Bern, Bern, Switzerland, Bern, Switzerland
    4. 4 CHU de Bordeaux, Bordeaux, France
    5. 5 Interventional Neuroradiology, CHU Limoges, Limoges, France
    6. 6 Department of Neuroradiolology, CHU Strasbourg, Strasbourg, France
    7. 7 Department of Vascular Neurology, Centre Hospitalier Regional Universitaire de Lille, Lille, France
    8. 8 Neurology Servcie, University of Lausanne, Lausanne, Switzerland
    9. 9 Departement of Interventional Neuroradiology, Fondation Rothschild Hospital, Paris, France
    10. 10 Neurology, GH Lariboisiere Fernand-Widal, Paris, France
    11. 11 University Hospital Zurich, Zurich, Switzerland
    12. 12 Neuroradiology, University Hospital of Tours, Tours, France
    13. 13 Neuroradiology, Geneva University Hospitals, Geneve, Switzerland
    14. 14 Neurology, Toronto Western Hospital, Toronto, Ontario, Canada
    15. 15 Neuroradiology, CHRU de Brest, Brest, France
    16. 16 Neurosciences, Hospital Universitari Germans Trias i Pujol, Badalona, Spain
    17. 17 Neurology, Osnabruck Hospital, Osnabruck, Niedersachsen, Germany
    18. 18 Neurology, GHU Paris Psychiatrie et Neurosciences, Paris, France
    19. 19 Université Paris Cité, Paris, France
    20. 20 INSERM U1266, Paris, France
    21. 21 FHU Neurovasc, Paris, France
    22. 22 Department of Neurology, University of California Los Angeles, Los Angeles, California, USA
    23. 23 Department for Diagnostic and Interventional Neuroradiology, Inselspital, University of Bern, Bern, Switzerland
    24. 24 Department of Neurology, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland
    1. Correspondence to Dr Gaultier Marnat, Interventional and Diagnostic Neuroradiology, University Hospital Centre Bordeaux, Bordeaux, Aquitaine, France; gaultier.marnat{at}chu-bordeaux.fr

    Abstract

    Background In proximal occlusions, the effect of reperfusion therapies may differ between slow or fast progressors. We investigated the effect of intravenous thrombolysis (IVT) (with alteplase) plus mechanical thrombectomy (MT) versus thrombectomy alone among slow versus fast stroke progressors.

    Methods The SWIFT-DIRECT trial data were analyzed: 408 patients randomized to IVT+MT or MT alone. Infarct growth speed was defined by the number of points of decay in the initial Alberta Stroke Program Early CT Score (ASPECTS) divided by the onset-to-imaging time. The primary endpoint was 3-month functional independence (modified Rankin scale 0–2). In the primary analysis, the study population was dichotomized into slow and fast progressors using median infarct growth velocity. Secondary analysis was also conducted using quartiles of ASPECTS decay.

    Results We included 376 patients: 191 IVT+MT, 185 MT alone; median age 73 years (IQR 65–81); median initial National Institutes of Health Stroke Scale (NIHSS) 17 (IQR 13–20). The median infarct growth velocity was 1.2 points/hour. Overall, we did not observe a significant interaction between the infarct growth speed and the allocation to either randomization group on the odds of favourable outcome (P=0.68). In the IVT+MT group, odds of any intracranial hemorrhage (ICH) were significantly lower in slow progressors (22.8% vs 36.4%; OR 0.52, 95% CI 0.27 to 0.98) and higher among fast progressors (49.4% vs 26.8%; OR 2.62, 95% CI 1.42 to 4.82) (P value for interaction <0.001). Similar results were observed in secondary analyses.

    Conclusion In this SWIFT-DIRECT subanalysis, we did not find evidence for a significant interaction of the velocity of infarct growth on the odds of favourable outcome according to treatment by MT alone or combined IVT+MT. However, prior IVT was associated with significantly reduced occurrence of any ICH among slow progressors whereas this was increased in fast progressors.

    • stroke
    • thrombectomy
    • thrombolysis
    • hemorrhage

    Data availability statement

    Data are available upon reasonable request. The data supporting this study are available upon reasonable request.

    https://doi.org/10.1136/jnis-2023-020113

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      Data availability statement

      Data are available upon reasonable request. The data supporting this study are available upon reasonable request.

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      Footnotes

      • Twitter @FishingNeurons

      • Collaborators SWIFT-DIRECT investigators: Urs Fischer, Johannes Kaesmacher, Daniel Strbian, Omer Eker, Christophe Cognard, Patricia S. Plattner, Lukas Bütikofer, Pasquale Mordasini, Sandro Deppeler, Vitor Mendes-Pereira, Jean François Albucher, Jean Darcourt, Romain Bourcier, Benoit Guillon, Chrysanthi Papagiannaki, Ozlem Ozkul-Wermester, Gerli Sibolt, Marjaana Tiainen, Benjamin Gory, Sébastien Richard, Jan Liman, Marielle Sophie Ernst, Marion Boulanger, Charlotte Barbier, Laura Mechtouff, Liqun Zhang, Gaultier Marnat, Igor Sibon, Omid Nikoubashman, Arno Reich, Arturo Consoli, Bertrand Lapergue, Marc Ribo, Alejandro Tomasello, Suzana Saleme, Francisco Macian, Solène Moulin, Paolo Pagano, Guillaume Salliou, Emmanuel Carrera, Kevin Janot, María Hernández-Pérez, Raoul Pop, Lucie Della Schiava, Andreas R. Luft, Michel Piotin, Jean-Christophe Gentric, Aleksandra Pikula, Waltraud Pfeilschifter, Marcel Arnold, Adnan H. Siddiqui, Michael T. Froehler, Anthony J. Furlan, René Chapot, Martin Wiesmann, Paolo Machi, Hans-Christoph Diener, Zsolt Kulcsar, Leo Bonati, Claudio L. Bassetti, Mikael Mazighi, David S. Liebeskind, Jeffrey L. Saver, Jan Gralla, Melanie Schmidhalter, Jenny Bressan, Stefanie Lerch, Andreas Limacher, Leonhard von Meyenn, Martina Zimmermann, Bruce Campbell, Tim Friede, Rüdiger von Kummer, Angelika Alonso, Caroline Arquizan, Xavier Barreau, Rémy Beaujeux, Daniel Behme, Tobias Boeckh-Behrens, Christian Boehme, Marti Boix, Grégoire Boulouis, Nicolas Bricout, Nicolas Broc, Carlo W. Cereda, Emmanuel Chabert, Tae-Hee Cho, Alessandro Cianfoni, Vincent Costalat, Christian Denier, Frederico Di Maria, Richard du Mesnil de Rochemont, Patricia Fearon, Anna Ferrier, Sebastian Fischer, Maxime Gauberti, Marie Gaudron, Laetitia Gimenez, Christoph Globas, Michael Görtler, Mayank Goyal, Ruediger Hilker-Roggendorf, Michael D. Hill, Vi Tuan Hua, Lisa Humbertjean, Olav Jansen, Simon Jung, Georg Kägi, Michael E. Kelly, Ilka Kleffner, Michael Knoflach, Krassen Nedeltchev, Lars Udo Krause, Kimmo Lappalainen, Margaux Lefebvre, Joe Leyon, Liang Liao, Jean-Sebastien Liegey, Christian Loehr, Patrik Michel, Stefania Nannoni, Patrick Nicholson, Lorena Nico, Michael Obadia, Julien Ognard, Ayokunle Ogungbemi, Jean-Marc Olivot, Simon Escalard, Marco Pasi, Lissa Peeling, Jane Perez, Martina Petersen, Eike Piechowiak, Roberto Raposo, Silja Räty, Sarah C. Reitz, Sebastià Remollo, Luca Remonda, Ian Rennie, Manuel Requena, Alexander Riabikin, Roberto Riva, Aymeric Rouchaud, Andrea Rosi, Marta Rubiera, Laurent Spelle, Marlena Schnieder, Joanna D. Schaafsma, Tilman Schubert, Jörg B. Schulz, Mohammed Siddiqui, Sébastien Soize, Michael Sonnberger, Emmanuel Touze, Aude Triquenot, Guillaume Turc, Lucy Vieira, Wagih Ben Hassen, Judith N. Wagner, Katrin Wasser, Johannes Weber, David Weisenburger-Lile, Fritz Wodarg, Valérie Wolff, Silke Wunderlich.

      • Contributors We attest that all authors have read and approved the submitted manuscript. All authors have made substantial contributions and have approved the final submitted version. GM, JK, LB, JG, UF acquired the data, analyzed the results, drafted the manuscript and critically reviewed the manuscript. GM, LB, JK and UF performed statistical analysis and analyzed the results. IS, SS, RP, HH, PM, MM, ZK, KJ, PM, AP, J-CG, MH-P, LUK, GT and DSL acquired the data and critically reviewed the manuscript. GM is the guarantor of the study.

      • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

      • Competing interests None declared.

      • Provenance and peer review Not commissioned; externally peer reviewed.

      • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.