Functional Outcome of Intravenous Thrombolysis in Patients With Lacunar Infarcts in the WAKE-UP Trial

Ewgenia Barow, Florent Boutitie, Bastian Cheng, Tae-Hee Cho, Martin Ebinger, Matthias Endres, Jochen B. Fiebach, Jens Fiehler, Ian Ford, Ivana Galinovic, Alina Nickel, Josep Puig, Pascal Roy, Anke Wouters, Tim Magnus, Vincent Thijs, Robin Lemmens, Keith W. Muir, Norbert Nighoghossian, Salvador PedrazaClaus Z. Simonsen, Christian Gerloff, Goetz Thomalla, Gotz Thomalla, Christian Gerloff, Amir Golsari, Anna Alegiani, Christoph Beck, Chi-un Choe, Dieke Voget, Julia Hoppe, Julian Schroder, Michal Rozanski, Alexander H. Nave, Christian Wollboldt, Ivana Galinovic, Isabelle van Sloten, Jos Gohler, Juliane Herm, Jan Jungehulsing, Janos Luckl, Jan M. Krober, Johannes Schurig, Luzie Koehler, Ludwig Schlemm, Michael Knops, Maria Roennefarth, Nils Ipsen, Peter Harmel, Rouven Bathe-Peters, Robert Fleischmann, Ramanan Ganeshan, Rohat Geran, Simon Hellwig, Sein Schmidt, Serdar Tutuncu, Thomas Krause, Verena Gramse, Joachim Rother, Peter Michels, Dominik Michalski, Johann Pelz, Andreas Schulz, Carsten Hobohm, Christopher Weise, Gesa Weise, Johannes Orthgiess, Katrin Pomrehn, Mirko Wegscheider, Anne K. Mueller, Michael Hennerici, Martin Griebe, Angelika Alonso, Alexandra Filipov, Annika Marzina, Bettina Anders, Christian Bahr, Carolin Hoyer, Christopher Schwarzbach, Claudia Weber, Eva Hornberger, Hans-Werner Pledl, Matti Klockziem, Markus Stuermlinger, Matthias Wittayer, Marc Wolf, Nadja Meyer, Philipp Eisele, Susanne Steinert, Tamara Sauer, Valentin Held, Peter Ringleb, Simon Nagel, Roland Veltkamp, Sonke Schwarting, Alexander Schwarz, Christoph Gumbinger, Christian Hametner, Hemasse Amiri, Jan Purrucker, Mareva Ciatipis, Oliver Menn, Sibu Mundiyanapurath, Simon Schieber, Tobias Kessler, Tilman Reiff, Verena Panitz, Oliver Singer, Christian Foerch, Arne Lauer, Anika Manner, Alexander Seiler, Damla Guerzoglu, Jan H. Schafer, Katharina Filipski, Matthias Lorenz, Natalia Kurka, Pia Zeiner, Waltraud Pfeilschifter, Rainer Dziewas, Jens Minnerup, Christian Albiker, Martin Ritter, Matthias Seidel, Ralf Dittrich, Bernd Kallmunzer, Tobias Bobinger, Dominik Madzar, David Stark, Jochen Sembill, Kosmas Macha, Klemens Winder, Lorenz Breuer, Martin Koehrmann, Maximilian Spruegel, Stefan Gerner, Sebastian Moeller, Peter Kraft, Daniel Mackenrodt, Christoph Kleinschnitz, Ahmed Elhfnawy, Florian Heinen, Ignaz Gunreben, Sven Poli, Ulf Ziemann, Alexandra Gaenslen, Dennis Schlak, Florian Haertig, Francesca Russo, Hardy Richter, Matthias Ebner, Martin Ribitsch, Martin Wolf, Christian Weimar, Vesna Zegarac, Hsin-Chieh Chen, Katharina Althaus, Hermann Neugebauer, Eric Juttler, Julia Meier, Sebastian Stosser, Volker Puetz, Ulf Bodechtel, Claus. Z. Simonsen, Leif Ostergaard, Anette Moller, Dorte Damgaard, Kristina Hougaard Dupont, Marika Poulsen, Niels Hjort, Noelia Ruiz de Morales, Paul von Weitzel, Thomas Harbo, Jacob Marstrand, Andreas Hansen, Hanne Christensen, Karen Aegidius, Lise Jeppesen, Per Meden, Sverre Rosenbaum, Helle Iversen, Christina Back, Jakob Hansen, Lene Michelsen, Thomas Truelsen, Boris Modrau, Bo Kristensen, Karsten Vestergaard, Lorenz Oppel, Robin Lemmens, Vincent Thijs, Anke Wouters, Bart Swinnen, Ide Smets, Jelle Demeestere, Laurens Dobbels, Raf Brouns, Ann De Smedt, Jacques DeKeyser, Laetita Yperzeele, Robbert-Jan Van Hooff, Andre Peeters, Anne Dusart, Ana Etexberria, Bernard Hanseeuw, Frederic London, Jonathan Leempoel, Katharina Hohenbichler, Nadia Younan, Vicky Maqueda, Patrice Laloux, Beatrijs De Coene, Charlotte De Maeseneire, Gaetane Turine, Yves Vandermeeren, Nina De Klippel, Chris Willems, Isabel de Hollander, Peter Soors, Sylvia Hermans, Dimitri Hemelsoet, Philippe Desfontaines, Peter Vanacker, Matthieu Rutgers, Charlotte Druart, Perrine Paindeville, Dirk Peeters, Bart Bruneel, Evelien Vancaester, Frederik Vanhee, Guy Meersman, Paul Bourgeois, Patrick Vanderdonckt, Norbert Nighoghossian, Amandine Benoit, Laurent Derex, Laura Mechthouff, Nadia Berhoune, Thomas Ritzenthaler, Pierre Amarenco, Cristina Hobeanu, Elena Meseguer Gancedo, David Calvet, Alexandre Ladoux, Alexandre Machet, Catherine Lamy, Charles Mellerio, Catherine Oppenheim, Christine Rodriguez-Regent, Eric Bodiguel, Guillaume Turc, Julia Birchenall, Laurence Legrand, Ludovic Morin, Myriam Edjali-Goujon, Oliver Naggara, Soulliard Raphaelle, Sylvie Godon-Hardy, Valerie Domigo, Vincent Guiraud, Yues Samson, Anne Leger, Charlotte Rosso, Flore Baronnet-Chauvet, Sophie Crozier, Sandrine Deltour, Marion Yger, Igor Sibon, Pauline Renou, Sharmilla Sagnier, Mathieu Zuber, Ruben Tamazyan, Gilles Rodier, Nathalie Morel, Sandra Felix, Wilfried Vadot, Valerie Wolff, Adriana Aniculaesei, Bertrand Yalo, Daniela Bindila, Veronique Quenardelle, Karine Blanc-Lasserre, Emmanuelle Landrault, Ludovic Breynaert, Serkan Cakmak, Stephane Peysson, Alain Viguier, Claire Lebely, Nicolas Raposo, Anne-Evelyne Vallet, Pauline Vallet, Sebastian Brugirard, Keith W. Muir, Bharath Cheripelli, Dheeraj Kalladka, Fiona Moreton, Krishna Dani, Salwa El Tawil, Sankaranarayanan Ramachandran, Xuya Huang, Elisabeth Warburton, Nicholas Evans, Richard Perry, Bhavni Patel, Geoffrey Cloud, Anthony Pereira, Barry Moynihan, Caroline Lovelock, Lillian Choy, Usman Khan, Christine Roffe, Pippa Tyrell, Craig Smith, Anand Dixit, Stephen Louw, David Broughton, Ashit Shetty, Jason Appleton, Nikola Sprigg, Salvador Pedraza Gutierrez, Boris Raul Acosta, Cecile van Eendenburg, Josep Puig Alcantara, Joaquin Serena Leal, Maria del Mar Castellanos Rodrigo, Mikel Terceno Izaga, Olga Belchi Guillamon, Juan Arenillas, Ana Calleja, Elisa Cortijo, Patricia Mulero, Natalia Perez de la Ossa, Alicia Garrido, Alicia Martinez, Carlos Garcia Esperon, Cristina Guerrero, David Carrera, Dolores Vilas, Elena Lopez-Cancio, Ernest Palomeras, Giuseppe Lucente, Meritxell Gomis, Irina Isern, Juan L. Becerra, Jose Hervas Vicente, Josep Sanchez, Laura Dorado, Laia Grau, Lourdes Ispierto, Luis Prats, Miriam Almendrote, Maria Hernandez, Marta Jimenez, Manuel Lozano Sanchez, Monica Millan Torne, Silvia Presas, Xavier Ustrell, Anna Pellise, Irene Navalpotro, Alain Luna, Wouter Schonewille, Paul Nederkoorn, Charles Majoie, Lucie van den Berg, Sophie van den Berg, Thomas Zonneveld, Michel Remmers, Franz Fazekas, Alexander Pichler, Simon Fandler, Thomas Gattringer, Johannes Mutzenbach, Jorg Weber, Elmar Hofner, Heinz Kohlfurst, Karin Weinstich, Lars Kellert, Anna Bayer-Karpinska, Christian Opherk, Frank Wollenweber, Matthias Klein, Tobias Neumann-Haefelin, Alexandra Pierskalla, Andreas Harloff, Jurgen Bardutzky, Florian Buggle, Jorg von Schrader, Rainer Kollmar, Josef Schill, Anna-Mareike Lobbe, Thierry Moulin, Benjamin Bouamra, Louise Bonnet, Emmanuel Touze, Anne-Laure Bonnet, Emmanuel Touze, Julien Cogez, Lin Li, Sophie Guettier, Arindam Kar, Aravinth Sivagnanaratham, Olivia Geraghty, Urszula Bojaryn, Arumugam Nallasivan, Miguel Blanco Gonzales, Manuel Rodriguez-Yanez, Jose Tembl, David Gorriz, Stefan Oberndorfer, Elisabeth Prohaska

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Importance: The rationale for intravenous thrombolysis in patients with lacunar infarcts is debated, since it is hypothesized that the microvascular occlusion underlying lacunar infarcts might not be susceptible to pharmacological reperfusion treatment. Objective: To study the efficacy and safety of intravenous thrombolysis among patients with lacunar infarcts. Design, Setting, and Participants: This exploratory secondary post hoc analysis of the WAKE-UP trial included patients who were screened and enrolled between September 2012 and June 2017 (with final follow-up in September 2017). The WAKE-UP trial was a multicenter, double-blind, placebo-controlled randomized clinical trial to study the efficacy and safety of intravenous thrombolysis with alteplase in patients with an acute stroke of unknown onset time, guided by magnetic resonance imaging. All 503 patients randomized in the WAKE-UP trial were reviewed for lacunar infarcts. Diagnosis of lacunar infarcts was based on magnetic resonance imaging and made by consensus of 2 independent investigators blinded to clinical information. Main Outcomes and Measures: The primary efficacy variable was favorable outcome defined by a score of 0 to 1 on the modified Rankin Scale at 90 days after stroke, adjusted for age and severity of symptoms. Results: Of the 503 patients randomized in the WAKE-UP trial, 108 patients (including 74 men [68.5%]) had imaging-defined lacunar infarcts, whereas 395 patients (including 251 men [63.5%]) had nonlacunar infarcts. Patients with lacunar infarcts were younger than patients with nonlacunar infarcts (mean age [SD], 63 [12] years vs 66 [12] years; P =.003). Of patients with lacunar infarcts, 55 (50.9%) were assigned to treatment with alteplase and 53 (49.1%) to receive placebo. Treatment with alteplase was associated with higher odds of favorable outcome, with no heterogeneity of treatment outcome between lacunar and nonlacunar stroke subtypes. In patients with lacunar strokes, a favorable outcome was observed in 31 of 53 patients (59%) in the alteplase group compared with 24 of 52 patients (46%) in the placebo group (adjusted odds ratio [aOR], 1.67 [95% CI, 0.77-3.64]). There was 1 death and 1 symptomatic intracranial hemorrhage according to Safe Implementation of Thrombolysis in Stroke-Monitoring Study criteria in the alteplase group, while no death and no symptomatic intracranial hemorrhage occurred in the placebo group. The distribution of the modified Rankin Scale scores 90 days after stroke also showed a nonsignificant shift toward better outcomes in patients with lacunar infarcts treated with alteplase, with an adjusted common odds ratio of 1.94 (95% CI, 0.95-3.93). Conclusions and Relevance: While the WAKE-UP trial was not powered to demonstrate the efficacy of treatment in subgroups of patients, the results indicate that the association of intravenous alteplase with functional outcome does not differ in patients with imaging-defined lacunar infarcts compared with those experiencing other stroke subtypes..

Original languageEnglish
Pages (from-to)641-649
Number of pages9
JournalJAMA Neurology
Volume76
Issue number6
DOIs
Publication statusPublished - Jun 2019

Cite this