Comparative Effects of Glenzocimab and Eptifibatide on Bleeding Severity in 2 Mouse Models of Intracranial Hemorrhage
Background Antiplatelet drugs represent potential candidates for protecting the penumbral microcirculation during cerebral ischemia and improving the benefits of arterial recanalization in ischemic stroke. Yet while the efficacy of such adjuvant strategies has been shown to be highly time dependent,...
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Wiley
2025-02-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
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| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.123.034207 |
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| author | Sébastien Dupont Héloïse Lebas Sabrina Mavouna Eloïse Pascal Astride Perrot Adrien Cogo Marie‐Charlotte Bourrienne Carine Farkh Mialitiana Solo Nomenjanahary Véronique Ollivier Fatima Zemali Bernhard Nieswandt Stéphane Loyau Martine Jandrot‐Perrus Eric Camerer Jean‐Philippe Desilles Mikael Mazighi Yacine Boulaftali Benoît Ho‐Tin‐Noé |
| author_facet | Sébastien Dupont Héloïse Lebas Sabrina Mavouna Eloïse Pascal Astride Perrot Adrien Cogo Marie‐Charlotte Bourrienne Carine Farkh Mialitiana Solo Nomenjanahary Véronique Ollivier Fatima Zemali Bernhard Nieswandt Stéphane Loyau Martine Jandrot‐Perrus Eric Camerer Jean‐Philippe Desilles Mikael Mazighi Yacine Boulaftali Benoît Ho‐Tin‐Noé |
| author_sort | Sébastien Dupont |
| collection | DOAJ |
| description | Background Antiplatelet drugs represent potential candidates for protecting the penumbral microcirculation during cerebral ischemia and improving the benefits of arterial recanalization in ischemic stroke. Yet while the efficacy of such adjuvant strategies has been shown to be highly time dependent, antiplatelet therapy at the acute phase of ischemic stroke cannot be envisioned until the diagnosis of stroke and its ischemic nature have been confirmed because of the presumed risk of worsening bleeding in case of intracranial hemorrhage (ICH). Here, we investigated this risk for 2 antiplatelet drugs currently being tested in clinical trials for ischemic stroke, glenzocimab and eptifibatide, in 2 mouse models of ICH. Methods and Results The severity of ICH was assessed in mice humanized for glycoprotein VI treated or not with glenzocimab or eptifibatide at effective dose, in a model of primary ICH caused by unilateral striatal injection of collagenase type VII, and in a model of hyperglycemia‐induced hemorrhagic transformation of cerebral ischemia–reperfusion injury. Glenzocimab had no impact on bleeding severity in either model of ICH. Conversely, eptifibatide caused a significant increase in intracranial bleeding in both models, and a drastic increase in death after hyperglycemia‐induced hemorrhagic transformation of cerebral ischemia–reperfusion injury. Conclusions Unlike eptifibatide, glenzocimab is safe in the setting of ICH. These results suggest that glenzocimab could be administered upon suspicion of ischemic stroke, before assessment of its ischemic nature, thus opening the way to hastening of treatment initiation. |
| format | Article |
| id | doaj-art-f0e19a3d29db4fb6943b805d728b88e7 |
| institution | Kabale University |
| issn | 2047-9980 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj-art-f0e19a3d29db4fb6943b805d728b88e72025-02-04T11:00:01ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802025-02-0114310.1161/JAHA.123.034207Comparative Effects of Glenzocimab and Eptifibatide on Bleeding Severity in 2 Mouse Models of Intracranial HemorrhageSébastien Dupont0Héloïse Lebas1Sabrina Mavouna2Eloïse Pascal3Astride Perrot4Adrien Cogo5Marie‐Charlotte Bourrienne6Carine Farkh7Mialitiana Solo Nomenjanahary8Véronique Ollivier9Fatima Zemali10Bernhard Nieswandt11Stéphane Loyau12Martine Jandrot‐Perrus13Eric Camerer14Jean‐Philippe Desilles15Mikael Mazighi16Yacine Boulaftali17Benoît Ho‐Tin‐Noé18Université Paris Cité, Inserm, UMRS‐1144, Optimisation Thérapeutique en Neuropsychopharmacologie Paris FranceUniversité Paris Cité, Inserm, UMRS‐1148, Laboratory for Vascular Translational Science Paris FranceUniversité Paris Cité, Inserm, UMRS‐1144, Optimisation Thérapeutique en Neuropsychopharmacologie Paris FranceUniversité Paris Cité, Inserm, UMRS‐1144, Optimisation Thérapeutique en Neuropsychopharmacologie Paris FranceUniversité Paris Cité, Inserm, UMRS‐1144, Optimisation Thérapeutique en Neuropsychopharmacologie Paris FranceUniversité Paris Cité, Inserm, UMRS‐1144, Optimisation Thérapeutique en Neuropsychopharmacologie Paris FranceUniversité Paris Cité, Inserm, UMRS‐1144, Optimisation Thérapeutique en Neuropsychopharmacologie Paris FranceUniversité Paris Cité, Inserm, UMRS‐1144, Optimisation Thérapeutique en Neuropsychopharmacologie Paris FranceUniversité Paris Cité, Inserm, UMRS‐1144, Optimisation Thérapeutique en Neuropsychopharmacologie Paris FranceUniversité Paris Cité, Inserm, UMRS‐1144, Optimisation Thérapeutique en Neuropsychopharmacologie Paris FranceUniversité Paris Cité, Inserm, UMRS‐1144, Optimisation Thérapeutique en Neuropsychopharmacologie Paris FranceInstitute of Experimental Biomedicine I, University Hospital, University of Würzburg Würzburg GermanyUniversité Paris Cité, Inserm, UMRS‐1148, Laboratory for Vascular Translational Science Paris FranceUniversité Paris Cité, Inserm, UMRS‐1148, Laboratory for Vascular Translational Science Paris FranceUniversité Paris Cité, Inserm, PARCC Paris FranceUniversité Paris Cité, Inserm, UMRS‐1144, Optimisation Thérapeutique en Neuropsychopharmacologie Paris FranceUniversité Paris Cité, Inserm, UMRS‐1144, Optimisation Thérapeutique en Neuropsychopharmacologie Paris FranceUniversité Paris Cité, Inserm, UMRS‐1148, Laboratory for Vascular Translational Science Paris FranceUniversité Paris Cité, Inserm, UMRS‐1144, Optimisation Thérapeutique en Neuropsychopharmacologie Paris FranceBackground Antiplatelet drugs represent potential candidates for protecting the penumbral microcirculation during cerebral ischemia and improving the benefits of arterial recanalization in ischemic stroke. Yet while the efficacy of such adjuvant strategies has been shown to be highly time dependent, antiplatelet therapy at the acute phase of ischemic stroke cannot be envisioned until the diagnosis of stroke and its ischemic nature have been confirmed because of the presumed risk of worsening bleeding in case of intracranial hemorrhage (ICH). Here, we investigated this risk for 2 antiplatelet drugs currently being tested in clinical trials for ischemic stroke, glenzocimab and eptifibatide, in 2 mouse models of ICH. Methods and Results The severity of ICH was assessed in mice humanized for glycoprotein VI treated or not with glenzocimab or eptifibatide at effective dose, in a model of primary ICH caused by unilateral striatal injection of collagenase type VII, and in a model of hyperglycemia‐induced hemorrhagic transformation of cerebral ischemia–reperfusion injury. Glenzocimab had no impact on bleeding severity in either model of ICH. Conversely, eptifibatide caused a significant increase in intracranial bleeding in both models, and a drastic increase in death after hyperglycemia‐induced hemorrhagic transformation of cerebral ischemia–reperfusion injury. Conclusions Unlike eptifibatide, glenzocimab is safe in the setting of ICH. These results suggest that glenzocimab could be administered upon suspicion of ischemic stroke, before assessment of its ischemic nature, thus opening the way to hastening of treatment initiation.https://www.ahajournals.org/doi/10.1161/JAHA.123.034207antiplatelet drugsintracranial hemorrhageischemic strokeplateletssafety |
| spellingShingle | Sébastien Dupont Héloïse Lebas Sabrina Mavouna Eloïse Pascal Astride Perrot Adrien Cogo Marie‐Charlotte Bourrienne Carine Farkh Mialitiana Solo Nomenjanahary Véronique Ollivier Fatima Zemali Bernhard Nieswandt Stéphane Loyau Martine Jandrot‐Perrus Eric Camerer Jean‐Philippe Desilles Mikael Mazighi Yacine Boulaftali Benoît Ho‐Tin‐Noé Comparative Effects of Glenzocimab and Eptifibatide on Bleeding Severity in 2 Mouse Models of Intracranial Hemorrhage Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease antiplatelet drugs intracranial hemorrhage ischemic stroke platelets safety |
| title | Comparative Effects of Glenzocimab and Eptifibatide on Bleeding Severity in 2 Mouse Models of Intracranial Hemorrhage |
| title_full | Comparative Effects of Glenzocimab and Eptifibatide on Bleeding Severity in 2 Mouse Models of Intracranial Hemorrhage |
| title_fullStr | Comparative Effects of Glenzocimab and Eptifibatide on Bleeding Severity in 2 Mouse Models of Intracranial Hemorrhage |
| title_full_unstemmed | Comparative Effects of Glenzocimab and Eptifibatide on Bleeding Severity in 2 Mouse Models of Intracranial Hemorrhage |
| title_short | Comparative Effects of Glenzocimab and Eptifibatide on Bleeding Severity in 2 Mouse Models of Intracranial Hemorrhage |
| title_sort | comparative effects of glenzocimab and eptifibatide on bleeding severity in 2 mouse models of intracranial hemorrhage |
| topic | antiplatelet drugs intracranial hemorrhage ischemic stroke platelets safety |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.123.034207 |
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