Genetic and platelet function testing of ...
Type de document :
Compte-rendu et recension critique d'ouvrage
PMID :
Titre :
Genetic and platelet function testing of antiplatelet therapy for percutaneous coronary intervention: the ARCTIC-GENE study
Auteur(s) :
Collet, Jean-Philippe [Auteur]
Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases [ICAN]
Institut de cardiologie [CHU Pitié-Salpêtrière]
Hulot, Jean-Sébastien [Auteur]
Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases [ICAN]
Institut de cardiologie [CHU Pitié-Salpêtrière]
Cuisset, Thomas [Auteur]
Département de Cardiologie [Hôpital de la Timone - APHM]
Range, Grégoire [Auteur]
Hôpitaux de Chartres [Chartres]
Cayla, Guillaume [Auteur]
Centre Hospitalier Universitaire de Nîmes [CHU Nîmes]
Université de Montpellier [UM]
van Belle, Éric [Auteur]
Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 [RNMCD]
Elhadad, Simon [Auteur]
Rousseau, Hélène [Auteur]
Hôpital Lariboisière
Sabouret, Pierre [Auteur]
Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases [ICAN]
Institut de cardiologie [CHU Pitié-Salpêtrière]
O'Connor, Stephen [Auteur]
Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases [ICAN]
Institut de cardiologie [CHU Pitié-Salpêtrière]
Abtan, Jérémie [Auteur]
Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases [ICAN]
Institut de cardiologie [CHU Pitié-Salpêtrière]
Kerneis, Mathieu [Auteur]
Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases [ICAN]
Institut de cardiologie [CHU Pitié-Salpêtrière]
Saint-Etienne, Christophe [Auteur]
Centre Hospitalier Régional Universitaire de Tours [CHRU Tours]
Barthelemy, Olivier [Auteur]
Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases [ICAN]
Institut de cardiologie [CHU Pitié-Salpêtrière]
Beygui, Farzin [Auteur]
CHU Caen
Silvain, Johanne [Auteur]
Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases [ICAN]
Institut de cardiologie [CHU Pitié-Salpêtrière]
Vicaut, Éric [Auteur]
Hôpital Lariboisière
Montalescot, Gilles [Auteur]
Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases [ICAN]
Institut de cardiologie [CHU Pitié-Salpêtrière]
Investigators, Arctic [Auteur]
Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases [ICAN]
Institut de cardiologie [CHU Pitié-Salpêtrière]
Hulot, Jean-Sébastien [Auteur]
Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases [ICAN]
Institut de cardiologie [CHU Pitié-Salpêtrière]
Cuisset, Thomas [Auteur]
Département de Cardiologie [Hôpital de la Timone - APHM]
Range, Grégoire [Auteur]
Hôpitaux de Chartres [Chartres]
Cayla, Guillaume [Auteur]
Centre Hospitalier Universitaire de Nîmes [CHU Nîmes]
Université de Montpellier [UM]
van Belle, Éric [Auteur]
Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 [RNMCD]
Elhadad, Simon [Auteur]
Rousseau, Hélène [Auteur]
Hôpital Lariboisière
Sabouret, Pierre [Auteur]
Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases [ICAN]
Institut de cardiologie [CHU Pitié-Salpêtrière]
O'Connor, Stephen [Auteur]
Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases [ICAN]
Institut de cardiologie [CHU Pitié-Salpêtrière]
Abtan, Jérémie [Auteur]
Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases [ICAN]
Institut de cardiologie [CHU Pitié-Salpêtrière]
Kerneis, Mathieu [Auteur]
Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases [ICAN]
Institut de cardiologie [CHU Pitié-Salpêtrière]
Saint-Etienne, Christophe [Auteur]
Centre Hospitalier Régional Universitaire de Tours [CHRU Tours]
Barthelemy, Olivier [Auteur]
Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases [ICAN]
Institut de cardiologie [CHU Pitié-Salpêtrière]
Beygui, Farzin [Auteur]
CHU Caen
Silvain, Johanne [Auteur]
Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases [ICAN]
Institut de cardiologie [CHU Pitié-Salpêtrière]
Vicaut, Éric [Auteur]
Hôpital Lariboisière
Montalescot, Gilles [Auteur]
Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases [ICAN]
Institut de cardiologie [CHU Pitié-Salpêtrière]
Investigators, Arctic [Auteur]
Titre de la revue :
European journal of clinical pharmacology
Pagination :
1315 - 1324
Éditeur :
Springer Verlag
Date de publication :
2015-11
ISSN :
0031-6970
Mot(s)-clé(s) en anglais :
Antiplatelet therapy
Clopidogrel
Pharmacogenetic
Platelet reactivity
Stent thrombosis
Clopidogrel
Pharmacogenetic
Platelet reactivity
Stent thrombosis
Discipline(s) HAL :
Sciences du Vivant [q-bio]/Sciences pharmaceutiques/Pharmacologie
Résumé en anglais : [en]
BACKGROUND:The ARCTIC study randomized 2440 patients scheduled for stent implantation to a strategy of platelet function monitoring with drug adjustment in patients who had a poor response to antiplatelet therapy or to a ...
Lire la suite >BACKGROUND:The ARCTIC study randomized 2440 patients scheduled for stent implantation to a strategy of platelet function monitoring with drug adjustment in patients who had a poor response to antiplatelet therapy or to a conventional strategy without monitoring and drug adjustment. No significant improvement in clinical outcomes with platelet function monitoring was observed.OBJECTIVE:The purpose of this study is to assess the relationships between CYP2C19 genotypes, clopidogrel pharmacodynamic response, and clinical outcome.METHODS AND RESULTS:In the ARCTIC-GENE study, 1394 patients were genotyped for loss- and gain-of-function CYP2C19 alleles. Randomization of treatment strategy was well balanced. Slow metabolizers identified as carriers of at least one loss-of-function allele CYP2C19*2 (n = 459) were more likely poor responders at randomization (41.6 vs. 31.6%, p = 0.0112) and 14 days later (23.8 vs. 10.4%, p < 0.0001) and more frequently on prasugrel (11.5 vs. 8.1%, p = 0.039) as compared with rapid metabolizers (n = 935). Intensification of antiplatelet treatment did not differ between slow and rapid metabolizers according to the study algorithm based on platelet function only. The primary study outcome defined as the composite of death, myocardial infarction, stent thrombosis, stroke, or urgent revascularization 1 year after stent implantation did not differ between slow and rapid metabolizers (HR 0.988, 95% CI [0.812;1.202], p = 0.90). Likewise, the primary safety outcome did not differ between rapid and slow metabolizer phenotype.CONCLUSIONS:The genetic clopidogrel profile was a good marker of platelet function response on clopidogrel but was not related to clinical outcome suggesting that the genetic added little to the pharmacodynamic information used in the study to adjust antiplatelet therapy. ClinicalTrials.gov: NCT00827411.Lire moins >
Lire la suite >BACKGROUND:The ARCTIC study randomized 2440 patients scheduled for stent implantation to a strategy of platelet function monitoring with drug adjustment in patients who had a poor response to antiplatelet therapy or to a conventional strategy without monitoring and drug adjustment. No significant improvement in clinical outcomes with platelet function monitoring was observed.OBJECTIVE:The purpose of this study is to assess the relationships between CYP2C19 genotypes, clopidogrel pharmacodynamic response, and clinical outcome.METHODS AND RESULTS:In the ARCTIC-GENE study, 1394 patients were genotyped for loss- and gain-of-function CYP2C19 alleles. Randomization of treatment strategy was well balanced. Slow metabolizers identified as carriers of at least one loss-of-function allele CYP2C19*2 (n = 459) were more likely poor responders at randomization (41.6 vs. 31.6%, p = 0.0112) and 14 days later (23.8 vs. 10.4%, p < 0.0001) and more frequently on prasugrel (11.5 vs. 8.1%, p = 0.039) as compared with rapid metabolizers (n = 935). Intensification of antiplatelet treatment did not differ between slow and rapid metabolizers according to the study algorithm based on platelet function only. The primary study outcome defined as the composite of death, myocardial infarction, stent thrombosis, stroke, or urgent revascularization 1 year after stent implantation did not differ between slow and rapid metabolizers (HR 0.988, 95% CI [0.812;1.202], p = 0.90). Likewise, the primary safety outcome did not differ between rapid and slow metabolizer phenotype.CONCLUSIONS:The genetic clopidogrel profile was a good marker of platelet function response on clopidogrel but was not related to clinical outcome suggesting that the genetic added little to the pharmacodynamic information used in the study to adjust antiplatelet therapy. ClinicalTrials.gov: NCT00827411.Lire moins >
Langue :
Anglais
Vulgarisation :
Non
Source :