Accès ouvert déclaré 2024 article

Effect of the Factor XIa Inhibitor Asundexian According to Baseline Infarct Pattern and on MRI Covert Infarct Outcomes

Eric Edward Smith, Ashkan Shoamanesh, Lizhen Xu, Laura Heenan, Feryal Saad, Pablo C. Colorado, Chih‐Hao Chen, Robin Lemmens, Gian Marco De Marchis, Valeria Caso, Jaime Masjuán, Teruyuki Hirano, Ivan Gospodinov Milanov, Bruce C.V. Campbell, Jean‐Louis Mas, Stuart J. Connolly, Hardi Mundl, Robert G. Hart, Peter Bailey, Timothy John Kleinig, Dennis John Cordato, Philip M. C. Choi, Carlos García-Esperón, Andrew Chew, Geoffrey C. CLOUD, Vimal Stanislaus, Maurício da Silva Krause, Miriam L. Priglinger, Rohan Grimley, Darshan Ghia, Ramesh Sahathevan, Henry G. Brown, Chiu‐Yin Kwan, Michael J. Devlin, Stefan Greisenegger, S. Bonelli-Nauer, Jakob Rath, A. Langer, Martha Marko, Jéssica Tonin Ferrari, Alexandra Bernegger, Melanie Baumgartinger, Matthias Vigl, Stefan Krebs, W. Lang, M. Knoflach, Benjamin Dejakum, Sophia Zollner-Kiechl, Thomas Töll, Lena Domig, Johannes Sebastian Mutzenbach, Bernhard Ganser, Constantin Hecker, Cornelia Rösler, Nele Bubel, Slaven Pikija, Tobias Zellner, Ursula Leitner, Otto Berger, Birgit Surböck, Sebastian Beirer, Dimitre Staykov, Daniel Schrammel, Altuna Halilović, Michael Frattner, D. Barmherzigen, Christian Lampl, Christopher Hofer, S. Nagl, Christoph Bocksrucker, Jelle Demeestere, P. Desfontaines, C Ciobanu, Adinda De Pauw, Annelies Terwecoren, M.C. Hasenbroekx, Fiona M Clement, Nina De Klippel, Peter Soors, Sabine Hermans, Sylvie De Raedt, Fenne Vandervorst, Laura Seynaeve, Niels Fockaert, Sofie de Smet, Matthieu Pierre Rutgers, Nicole Del Gaudio, Perrine Paindeville, Ivan N. Staikov, A. Simeonova, Irina Ivanova Stoyanova, Maria Cholakova, Nikolay Mihnev, T. Petrova, A. Koralova, Daniel Dimov, Y. Kuzev, Maya Danovska, Diana L. Marinova, Diana Marinova-Trifonova, Emilia Ovcharova, Igor Mladenovski, Magdalina Yanakieva, Павел Стоев, Mariya Dimitrova, S. Todorova-Georgieva, L. Haralanov, B. Milkov, D. Solakov, Neli Petkova, V. Ignatova-Valkova, Vesselin Karabinov, Y. Miteva, V. Andonova, D. Kasabova, E. Kostadinova, Y. Shopova-Vrabcheva, D. Gatev, Dimitrina Jivkova Semova, Eray Halil, Ara G. Kaprelyan, Borko Ivanov, G. V. Panov, Маргарита Грудкова, N. Syuleyman, R. Kalpachki, Filip Alexiev, I. Ivanova, K. Kancheva, Teodora Sakelarova, Dimitar B. Maslarov, Desislava Drenska, Vasil Georgiev, Е. Б. Петрова, N. V. Petrova, N. Semerdjieva, P. Zhelyazkov, S. Spasova-Markova, Xiaofeng Dong, Defeng Wang, Scarlett Wang, W. Huang, Hui Zhao, Carolyn Wang, Jie Lu, Y. Xinyang, Qiang Dong, Yan‐Jiang Wang, W. Yue, Rui Liu, Y Yang, Petr Mikulenka, Peter Vaško, Tomáš Peisker, Michal Bar, Martin Roubec, Robert Mikulík, M. Cabukova, Jan Vinklárek, M. Pansky, Pavel Mencl, Ondřej Škoda, M. Carek, Marek Pernicka, M Skodová, Petr Geier, Jitka Čepková, Jakub Drlík, Tomáš Prax, R H Herzig, Dagmar Krajíčková, Eva Vítková, Simona Halúsková, Daniel Václavík, J Martínková, Katerina Blejcharova, M. Tkacova, O. Pavlik, Miroslava Nevšímalová, J. Rosol, Radovan Hrubý, Helle Klingenberg Iversen, Adam Vittrup Andersen, D. Rahimi, Hanne Christensen, Josefine Liv Gilling Grundtvig, Niels Hjort, Gary L. Andersen, Birgitte Forsom Sandal, Morten Stilund, Boris Modrau, A. Strade, Mirko Porobić, Søren Due Andersen, Christina Rostrup Kruuse, Joakim N.E. Ölmestig, Mia Kolmos, Md. Anowar Khasru Parvez, Thomas Christensen, Jakob Stokholm, Henrik Boye Jensen, Jukka Putaala, Daniel Strbian, Gerli Sibolt, Marjaana Tiainen, Nicolas Martinez‐Majander, Sami Curtze, Silja Räty, Yvonn Kraemer, Risto O. Roine, Julia Åivo, Juhani Ruuskanen, Pauli Ylikotila, Susanna Roine, Merja Hallikainen, Pekka A. Jäkälä, Sudhir Kurl, Valtteri Julkunen, Igor Sibon, Stéphane Olindo, Sébastien Richard, Vincent Larrue, Cédric Gollion, Hélène Catalá, Hilde Hénon, D.S. Lucie, D. Nelly, D. Calvet, A. Malbranque, Béatrice Mazé, C. Barbieux-Ghitu, G.H. Pitie Salpetriere, Charlotte Rosso, Yves Samson, Stéphane Vannier, Thierry Moulin, Louise Bonnet, Peggy Reiner, Frédérique Buffon, Christian Denier, K. Amri, Nicolas Legris, O. Chassin, N. Selli, S. Mariana, J. Berrouschot, Anett Stoll, Dietrich Klunk, Janina Keilitz, M. Neustadt, S. Zerrenner, Roland C. Veltkamp, Karim Hajjar, Allen P. Heeger, E. Winezki, L. Apel, Mosche Pompsch, Paul S. Mueller, P Rappard, Rebecca C. Auer, Peter Arthur Ringleb, Anne Berberich, Miriam Heyse, Sibu Mundiyanapurath, Tilman Reiff, Sven Poli, Antonio Gómez‐Expósito, Annerose Mengel, Johannes Tünnerhoff, Kazeem Dauda Adeyemi, Khouloud Poli, V. Kusch, Johann Otto Pelz, Dominik Michalski, Katja E. Wartenberg, Katharina Althaus, Fernando Gomes de Oliveira Tavares, Silvana Mueller, Hassan Soda, A. Rascher, Erich Hiermann, Renate Weinhardt, Karin Weißenborn, Andrei Leotescu, Gerrit Maximilian Große, Hans Worthmann, Jonna Ernst, Maria Magdalena Gabriel, Ramona Schuppner, Jan Hendrik Schäfer, Daniel Charissé, Kenneth A. Gruber, Natalia Kurka, Sarah Christina Reitz, Waltraud Pfeilschifter, J.I. Lee, Michael Gliem, M. Moll, Thorsten Steiner, Luís Segura, N. Szegedi, D. Barandi, L. Uhrinakova, Máté Czencz, Monika Pasztor, N. Gyuker, N.E. Bartha, Zsolt May, Z. Simony, Gábor Szász, Ilona Kakuk, N. Pető, Gitta Pánczél, Anna V. Oláh, Olivér Rácz, Tamás Balla, Balázs Zsigmond Horváth, Kaygusuz Tuba, V. Czinderi, Péter Klivènyi, Ádám Annus, Péter Hertelendy, László Botond Szapáry, Edit Bosnyák, Peter I. Kalmar, Zoltán Karádi, L. Cziba, László Oláh, Agnes Berki, Lauren A. Hudak, M Kozák, S. Babel, László Németh, B Molnár, Zsófia Simon, Luisa Roveri, F. Cerri, G. Giacalone, Andrea Zini, Guillermo Jesús Mauro, Gian Maria Asioli, Stefano Forlivesi, Giorgia Arnone, Anna Fiaccadori, E. Maria Fontana Francesca, Giovanni Allegra, Maria Giulia Mosconi, M. Longoni, Raffaele Terlizzi, Marco Paolucci, Rossana Tassi, Beatrice Franci, Barbara Lucani, Carlo Domenichelli, D. Paoletti, Maurizio Acampa, Marialuisa Zedde, Francesca Romana Pezzella, Marilena Mangiardi, Pietro Galizia, Sabrina Anticoli, Simona Scalise, Simona Lattanzi, Giuseppe Danilo Norata, M. Cannuccia, A. Cavallini, F. Federica, Maria Federica Denaro, Piera Tosi, Kazutaka Sonoda, Masakazu Kawajiri, Yusuke Kusano, Koichi Haraguchi, Hiroyuki Kawano, Tadashi Terasaki, Chinatsu Kaneko, Sho Murase, Morio Kumagai, Noriyuki Murai, Yoichi Miyazaki, Trevor Anthony Mori, Tatsuro Hatano, Masahiro Kawanishi, Jun Ochiai, Shin Ishihara, Toshiyuki Uehara, Masahiro Yasaka, Hidemitu Nakagawa, Masahiro Makino, Toshiro Yonehara, Yoshimitsu Fukushima, Nobuyuki Hirotsune, Norihiko Sakai, Masahiro Yamasaki, Jonathan M. Coutinho, Anke Wouters, Heleen den Hertog, R. Zwartbol, Debbie Beumer, Joost P. Kerklaan, Petra Hilkens, Tim H.A. Schreuder, DAVID J. PROPPER, Agnieszka Słowik, Elżbieta A. Włodarczyk, Paweł Wrona, Roman Pułyk, Anetta Lasek‐Bal, Katarzyna Kosarz-Lanczek, Przemysław Puz, Mehmet Zihni Bilik, A. Magielska, A. Zamiela – Żółciak, L. Ochocinska, S. Bahdasaryan, Adam Stępień, Aleksander Dȩbiec, S. Jacek, Pedro Modas Daniel, Sterpu-Clecicov Marta, Konrad Rejdak, Joanna Wojczal, Piotr Luchowski, Waldemar Fryze, Anna Wiśniewska, Monika Karolina Krzyzanowska, Piotr Mariusz Skowron, A. Wolosz, Amparo Galán, K. Grzymala, Magdalena Krajewska, Richard M. Nowak, Mariusz Kłos, Vincent B. Cruz, Pedro Castro, José Manuel Ferro, Patrícia Canhão, Rosa Henriques de Gouveia, N. Inácio, Miguel Rodrigues, Augusto Rachão, C Ionel, Lucas Henrique Matias Dias Pereira, Miguel Viana Baptista, Christian Machado, Carina Fernandes, J. Sargento, Lubov Timchenko, Julija Mironova, O. Zhadan, А. Н. Торгашова, O. K. Bazhenova, M. Barashenkova, M. Kireeva, N. Romadina, I I Stepanova, Liudmila G. Lenskaya, L. V. Lukinykh, Тамара Воронцова, Alina Agafina, Anna Fedorova, A.V. Yashina, Andrey Marisovich Alasheev, A. Smolkin, E. V. Prazdnichkova, Olga Y. Lutskovich, Y. Gonysheva, Elena Mordvintseva, Alexander N. Nechaev, E. Martynova, N. Fedoraeva, T. Vishnyakova, D. Popov, A. Merzliakova, L. Rechkalova, A E Ilyina, N. Kurenkova, О. Л. Барбараш, Evgeny D. Bazdyrev, Tatyana Nikolaevna Zvereva, A. М. Hromova, А А Морквенас, E. Postnikova, Galina A. Kovalenko, L. Pavlov, Martin Ott, N. Chernitsova, N. I. Vodopyanova, E. Drozdova, E. Korebo, M. Lobanova, Natalia B. Lazareva, Н Ф Снегова, Ольга Викторовна Николаева, Yuri A. Kolesnikov, Y. Kosheleva, Georgi Krastev, K. Tomasova, M. Danis, Mary E. Mako, Z. Jankovicova, Zuzana Števková, Michal Kováčik, Tereza Kubíková, Alžběta Jarošová, Vlastimil Serdahely, I. Cilingova, I. Pribulova, J. Sedlak, K. Slebodova, M. Paldaufova, Richard Risnovsky, B. Berndtova, Ivana Urbanova, R. Junas, S A Karapetian, Ladislav Gurcik, A. Vantrobova, F. Verbovsky, K. Vanacka, M. Ferenc, P.K. Galik, S. Bucakova, M. Ferencova, P. Kubalova, Z. Boksanska, E. Y. Zacharova, Evance Mahundi, H. Judita, M. Bachnak, Peter Turčáni, A. Kvasnicova Kamenska, M. Jurik, Veronika Vestenicka, Marian Kycina, E. Sagatova, M. Dvorak, A. Hlubekova, Courtney J. Kucera, L. Gernath, P. Frimmelova, J. Slebodnikova, N. Aksteinerova, V. Horny, Z. Gregova, Tomás Segura, Carlos Jiménez Romero, Ó. Ayo, J. Masjuan Vallejo, Aurelio Cruz-Valdéz, María-Consuelo Matute, Santiago García, José Tembl Ferrairo, I. Vielba, L. Morales Caba, Carlos Alberto Molina, R. Noelia, Manuel Rodríguez‐Yáñez, E. Rodriguez Castro, I. Lopez, Matteo Santamaria, S. Arias, Daniel Vázquez Justes, Gerard Mauri, Mikel Vicente Pascual, Pol Camps‐Renom, Ana Rodríguez-Campello, Eva Giralt, Jerzy Krupiński, José Molina, C. Ramos Martin S. Trillo Senin, E. De La Fuente Sanz, Francisco Moniche, M.R. Manuel, B. Pardo, I. Martínez, M Hernández Pérez, Juan Francisco Arenillas Lara, José Antonio Egido, Carlos Gómez Escalonilla, Marta Guillán, J. Martinez, Arne G. Lindgren, Gunnar Andsberg, Lars Wictor, M. Leonidou, Maria Stenman, N. Dalberg, Ann Charlotte Laska, A. Grünfeldt, A. Lundström, E. Nadzjafov, Elisabeth Rooth, I. Dalenbring, Per Sandén, Elias P Johansson, George Thomas, Annaelle Zietz, Stephen Rudin, Teri Dittrich, Georg Kägi, Jochen Vehoff, M Arnold, Adrian Scutelnic, Leander Clénin, Morin Beyeler, M. Madlaine, Basel Maamari, Bernhard Siepen, Jan Vynckier, Alexander Andrea Tarnutzer, D. Bertschi, Michelangelo Luciani, Carlo W. Cereda, Francesco Maulucci, Giovanni Bianco, S. Shairin, H.A. Pihan, Anke Salmen, Terence J. Quinn, Cameron S. McAlpine, Fiona Wright, Dheeraj Kalladka, Emma Taylor, J. Sohaa, Zoe Brown, Jesse Dawson, Alan Cameron, S. Muir, Sofia Dima, Uzma Rahim Khan, Lei Zhang, Elizabeth A. Warburton, Kausik Chatterjee, Arumugam Nallasivan, Desmond Curran, S. Haider, Usman Ghani, Anthony Kenton, Bander Dallol, Muhammad Mirza, Brian Menezes, Richard Davies, Thompson Gordon Robinson, Lisa S. Manning, L. Sztriha, Trevor A. Phinney, P.K. Sethi, Irfan Altafullah, Ahmed Lotfy Sharaf, Michael Ostrander, Swetha Renati, William Scott Burgin, K. Olds, Philip R. Delio, Ali R. Malek, Jonathan Dissin, Pooja Kumari Khatri, Michael R. Flaherty, Stacie L Demel, S. Dofitas

13Citations signalées, ce qui n’est pas une note de qualité

20Institutions déclarées

12Pays d’affiliation déclarés

Rattachement africain : ca, us, tw, be, ch, it, es, jp, bg, au, fr, de. Niveau de preuve : code pays fourni par la source.

Le résumé fourni par la source

BACKGROUND: Exploratory analysis of the phase 2 PACIFIC-Stroke (Program of Anticoagulation via Inhibition of FXIa by the Oral Compound BAY 2433334-Non-Cardioembolic Stroke) randomized trial suggested that asundexian, an oral factor XIa inhibitor, prevents recurrent stroke and transient ischemic attacks in patients with atherosclerotic stroke. In this post hoc exploratory analysis, we hypothesized that asundexian would be more effective in patients enrolled with large, multiple, or cortical acute infarcts on magnetic resonance imaging than in patients enrolled with a single small subcortical acute infarct, and asundexian would prevent incident cortical covert infarcts. METHODS: In this placebo-controlled double-blinded randomized controlled trial, patients with mild-to-moderate noncardioembolic ischemic stroke were assigned to asundexian (10, 20, or 50 mg once daily) or placebo, in addition to antiplatelet therapy. Brain magnetic resonance imagings were required within 72 hours of randomization and repeated at 26 weeks or at discontinuation of the study drug. RESULTS: Of 1808 randomized patients, 1780 (98.5%) had interpretable baseline magnetic resonance imagings, of which 1628 (91.5%) had ≥1 diffusion-weighted imaging positive acute infarcts. Magnetic resonance imaging follow-up was obtained in 1439 patients, of whom 1358 had no symptomatic stroke during the trial period. Compared with placebo, asundexian 50 mg daily conferred a trend toward reduced risk of recurrent ischemic stroke or incident covert infarcts (hazard ratio, 0.71 [95% CI, 0.45-1.11]) and recurrent ischemic stroke or transient ischemic attack (secondary outcome; hazard ratio, 0.59 [95% CI, 0.33-1.06]) that was not evident in patients with single small subcortical infarcts (hazard ratios, 1.14 [95% CI, 0.62-2.10] and 0.93 [95% CI, 0.28-3.06]). Incident cortical covert infarcts were reduced in patients taking asundexian 50 mg, but the difference was not statistically significant (crude incidence ratio, 0.56 [95% CI, 0.28-1.12]). CONCLUSIONS: These exploratory, unconfirmed results suggest that asundexian may prevent new embolic infarcts but not small artery occlusion. The hypothesis that subtypes of covert brain infarcts respond differently to anticoagulant prevention should be tested in future trials. REGISTRATION: URL: https://clinicaltrials.gov; Unique identifier: NCT04304508.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.

Le contrôle bibliographique ouvert

DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.

Titre Crossref: Effect of the Factor XIa Inhibitor Asundexian According to Baseline Infarct Pattern and on MRI Covert Infarct Outcomes
Date Crossref: 01/02/2024
Éditeur: Ovid Technologies (Wolters Kluwer Health)
Type: journal-article

Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.

Où se fait cette recherche

University of Calgary Department of Clinical Neurosciences pays non établi dans la notice
Université ou école supérieure
Population Health Research Institute Department of Statistics pays non établi dans la notice
Établissement de santé
Bayer (United States) pays non établi dans la notice
Entreprise
National Taiwan University Hospital Department of Neurology pays non établi dans la notice
Établissement de santé
KU Leuven Department of Neurosciences pays non établi dans la notice
Université ou école supérieure
Kantonsspital St. Gallen pays non établi dans la notice
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University Hospital of Basel pays non établi dans la notice
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Ospedale Santa Maria pays non établi dans la notice
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Misericordia University pays non établi dans la notice
Université ou école supérieure
Universidad de Alcalá pays non établi dans la notice
Université ou école supérieure
Instituto Ramón y Cajal de Investigación Sanitaria Department of Neurology pays non établi dans la notice
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Université ou école supérieure

Department of Clinical Neurosciences — University of Calgary, Department of Statistics — Population Health Research Institute et Bayer (United States), avec 9 autres affiliations.

Une affiliation ne permet pas de déduire la nationalité d’un auteur.

Les sujets associés

Coagulation, Bradykinin, Polyphosphates, and AngioedemaAtrial Fibrillation Management and OutcomesParathyroid Disorders and Treatments

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