1. Blunting periprocedural myocardial necrosis: Rationale and design of the randomized ALPHEUS study
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François Jourda, Christophe Saint-Etienne, Luc Christiaens, Grégoire Rangé, Benoit Lattuca, Philippe Brunel, Paul Guedeney, Hervé Le Breton, Marie Hauguel-Moreau, Eric Vicaut, Anne Bellemain-Appaix, Jean-Louis Georges, Guillaume Cayla, Christophe Pouillot, Christophe Caussin, Gregory Ducrocq, Ziad Boueri, Farzin Beygui, Johanne Silvain, Thibault Lhermusier, Gilles Montalescot, Jean-Noël Labèque, Jean-Philippe Collet, Zuzana Motovska, Franck Boccara, Mohamad El Kasty, Raphaelle Dumaine, Jean-Guillaume Dillinger, Mikael Laredo, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases [IHU ICAN], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Service de cardiologie et de pathologie vasculaire [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de cardiologie [Chartres], Les hôpitaux de Chartres [Chartres], Marqueurs cardiovasculaires en situation de stress (MASCOT (UMR_S_942 / U942)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC)-Université Sorbonne Paris Nord, Hôpital de Bastia, Service de Cardiologie [Hôpital privé Dijon Bourgogne], Hôpital privé Dijon Bourgogne, Clinique Sainte Clotilde, Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de cardiologie [CHU de Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service de cardiologie [Centre Hospitalier de la Côte Basque, Bayonne], Centre Hospitalier de la Côte Basque, CHU Toulouse [Toulouse], Centre Hospitalier de Versailles André Mignot (CHV), Cardiology Department, Centre Hospitalier d'Antibes Juan les Pins, Antibes, Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Trousseau [APHP], Institut Mutualiste de Montsouris (IMM), Hôpital d'Auxerre, Partenaires INRAE, Grand Hôpital de l'Est Francilien (GHEF), Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC)-Université Sorbonne Paris Nord, AstraZeneca France Novartis Daiichi-Sankyo Bristol-Myers Squibb, BMS Eli Lilly and Company Bayer AstraZeneca France Boston Scientific Corporation, BSC Abbott Laboratories Medtronic Biotronik Fédération Française de Cardiologie, FFC, The ALPHEUS and the Bio-ALPHEUS studies are funded by the Fond de dotation ACTION ( www.action-fonds.org ) and a grant from AstraZeneca . The Bio-ALPHEUS study is also funded by the Institute of Cardiometabolism and Nutrition . The first draft of the paper was developed by Dr Silvain and Dr Montalescot, and all authors subsequently contributed to its development and final content and are solely responsible for the design and conduct of this study, all study analyses, the drafting and editing of the paper, and its final contents. AstraZeneca reviewed the manuscript and was allowed to make suggestions, but final content was determined by the authors., Dr Silvain reports receiving consulting and lecture or travel support from AstraZeneca, Bayer HealthCare SAS, Biotronik, BPI France, Boehringer Ingelheim France, CSL Behring SA, Gilead Science, Sanofi-Aventis France, Terumo France SAS, Abbott Medical France SAS, and Zoll and is a stockholder of Pharmaseeds. Dr Cayla reports speaker or congress fees and has received research grants/consultant fees/lectures fees from Amgen, AstraZeneca, Abbott, Bayer, Biotronik, Bristol-Myers Squibb, Pfizer, and Sanofi-Aventis. Dr Beygui reports receiving consulting and lecture fees from Astrazeneca, Bristol-Myers Squibb, Medtronic, Biosensors, Boston Scientific Institutional and research grants from Medtronic, Biosensors, Acist, and Boston scientific. Dr Rangé reports receiving speaker’s and/or consulting fees from Abbott. Dr Lattuca has received research grants from Biotronik, Boston Scientific, Daiichi-Sankyo, Fédération Française de Cardiologie, and Institute of CardioMetabolism and Nutrition, consultant fees from Daiichi-Sankyo and Eli Lilly, and lecture fees from AstraZeneca, Medtronic, and Novartis. Dr Collet reports receiving consulting and lecture fees from AstraZeneca, Bayer, Bristol-Myers Squibb, Fédération Française de Cardiologie, Lead-Up, Medtronic, MSD, Sanofi-Aventis, and WebMD. Dr Dillinger reports receiving consulting and lecture fees from AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb/Pfizer, and Sanofi and grants from Bayer, Bristol-Myers Squibb/Pfizer, and Biosensors. Dr Boueri reports receiving consulting and lecture fees from Novartis and Astra Zeneca. Dr Boccara reports consulting or speaker fees from Amgen, Gilead, ViiV Healthcare, Amgen, Sanofi, MSD, and Servier outside the submitted work. Dr Christiaens reports consulting or speaker fees from Astra Zeneca. Dr Lhermusier reports consulting or speaker fees from Astra Zeneca, Boston Scientifics, and Abbott and a research grant from Astra Zeneca. Dr Georges reports consulting or speaker fees from AstraZeneca France, Sanofi-Aventis, Amgen, and Merck Sharpe and Dohme. Dr Bellemain-Appaix reports consulting or speaker fees from Astra Zeneca, Novartis, and Pfizer. Dr Saint-Etienne reports consulting or speaker fees from Abbott, Medtronic, Edwards, and Biotronik. Dr Motovska reports consulting or speaker fees from Astrazeneca. Dr Laredo reports fellowship grants from Medtronic, Biotronik, and Boston Scientific. Dr Ducrocq reports consulting or speaker fees from Amgen, Astra Zeneca, Bayer, BMS, Janssen, Sanofi, and Terumo, proctoring: Boston scientific, CEC: Novo Nordisk, and travel fees: Astra Zeneca, Bayer, and BMS. Dr Vicaut reports consulting or speaker fees from Abbott, Bristol Myers Squibb, Celgene, Edwards, Pfizer, Sanofi, and Novartis. Dr Montalescot reports consulting or speaker fees from Abbott, AIM group, Amgen, Actelion, American College of Cardiology Foundation, Astrazeneca, Axis-Santé, Bayer, Boston-Scientific, Bristol-Myers Squibb, Beth Israel Deaconess Medical, Brigham Women’s Hospital, Fréquence Médicale, ICOM, Idorsia, Elsevier, Fédération Française de Cardiologie, Fréquence Médicale, Institute of Cardiometabolism and Nutrition, Lead-Up, Menarini, Medtronic, MSD, Novo-Nordisk, Pfizer, Quantum Genomics, Sanofi-Aventis, SCOR global life, Servier, and WebMD. Other authors have no conflict of interest to report., Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Université Sorbonne Paris Nord, Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Centre Hospitalier de la Côte Basque (CHCB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier d'Auxerre (CHA), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord
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medicine.medical_specialty ,Ticlopidine ,medicine.medical_treatment ,Myocardial Infarction ,Coronary Disease ,030204 cardiovascular system & hematology ,Coronary Angiography ,Loading dose ,Coronary artery disease ,03 medical and health sciences ,0302 clinical medicine ,Percutaneous Coronary Intervention ,[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system ,Internal medicine ,medicine ,Humans ,030212 general & internal medicine ,Myocardial infarction ,cardiovascular diseases ,Aged ,Aspirin ,business.industry ,Percutaneous coronary intervention ,medicine.disease ,Clopidogrel ,3. Good health ,Conventional PCI ,Cardiology ,Purinergic P2Y Receptor Antagonists ,[SDV.IB]Life Sciences [q-bio]/Bioengineering ,Cardiology and Cardiovascular Medicine ,business ,Ticagrelor ,Platelet Aggregation Inhibitors ,medicine.drug - Abstract
International audience; Background: Clopidogrel associated with aspirin is the recommended treatment for patients undergoing elective percutaneous coronary intervention (PCI). Although severe PCI-related events are rare, evidence suggests that PCI-related myocardial infarction and myocardial injury are frequent complications that can impact the clinical prognosis of the patients. Antiplatelet therapy with a potent P2Y12 receptor inhibitor such as ticagrelor may reduce periprocedural ischemic complications while maintaining a similar safety profile as compared with conventional dual antiplatelet therapy by aspirin and clopidogrel in this setting. Methods: Assessment of Loading with the P2Y12 inhibitor ticagrelor or clopidogrel to Halt ischemic Events in patients Undergoing elective coronary Stenting (ALPHEUS) (NCT02617290) is an international, multicenter, randomized, parallel-group, open-label study in patients with stable coronary artery disease who are planned for an elective PCI. In total, 1,900 patients will be randomized before a planned PCI to a loading dose of ticagrelor 180 mg or a loading dose of clopidogrel (300 or 600 mg) in addition to aspirin. Patients will then receive a dual antiplatelet therapy with aspirin and ticagrelor 90 mg twice daily or clopidogrel 75 mg once daily for 30 days. The primary ischemic end point is PCI-related myocardial infarction (myocardial infarction type 4a or 4b) or major myocardial injury within 48 hours (or at hospital discharge if earlier) after elective PCI/stent. Safety will be evaluated by major bleeding events (Bleeding Academic Research Consortium type 3 or 5) at 48 hours (or discharge if it occurs earlier). Conclusion: ALPHEUS is the first properly sized trial comparing ticagrelor to clopidogrel in the setting of elective PCI and is especially designed to show a reduction in periprocedural events, a surrogate end point for mortality.
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- 2020