Genetic and platelet function testing of antiplatelet therapy for percutaneous coronary intervention: the ARCTIC-GENE study
International audience 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 adjust...
Published in: | European Journal of Clinical Pharmacology |
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Main Authors: | , , , , , , , , , , , , , , , , , , |
Other Authors: | , , , , , , , , , , , , , , , , , , , , , |
Format: | Article in Journal/Newspaper |
Language: | English |
Published: |
HAL CCSD
2015
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Subjects: | |
Online Access: | https://hal.science/hal-01913502 https://doi.org/10.1007/s00228-015-1917-9 |
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ftunivlille:oai:HAL:hal-01913502v1 |
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Open Polar |
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LillOA (HAL Lille Open Archive, Université de Lille) |
op_collection_id |
ftunivlille |
language |
English |
topic |
Antiplatelet therapy Clopidogrel Pharmacogenetic Platelet reactivity Stent thrombosis [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology |
spellingShingle |
Antiplatelet therapy Clopidogrel Pharmacogenetic Platelet reactivity Stent thrombosis [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology Collet, Jean-Philippe Hulot, Jean-Sébastien Cuisset, Thomas Range, Grégoire Cayla, Guillaume van Belle, Éric Elhadad, Simon Rousseau, Hélène Sabouret, Pierre O'Connor, Stephen Abtan, Jérémie Kerneis, Mathieu Saint-Etienne, Christophe Barthelemy, Olivier Beygui, Farzin Silvain, Johanne Vicaut, Éric Montalescot, Gilles Investigators, Arctic Genetic and platelet function testing of antiplatelet therapy for percutaneous coronary intervention: the ARCTIC-GENE study |
topic_facet |
Antiplatelet therapy Clopidogrel Pharmacogenetic Platelet reactivity Stent thrombosis [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology |
description |
International audience 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. |
author2 |
Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN) Université Pierre et Marie Curie - Paris 6 (UPMC)-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) Institut de cardiologie CHU Pitié-Salpêtrière CHU Pitié-Salpêtrière 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) Département de Cardiologie Hôpital de la Timone - APHM Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Timone CHU - APHM (TIMONE) Hôpitaux de Chartres Chartres Centre Hospitalier Universitaire de Nîmes (CHU Nîmes) Université de Montpellier (UM) Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 (RNMCD) Institut Pasteur de Lille Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire CHU Lille (CHRU Lille) Service de Cardiologie Centre Hospitalier Lagny-Marne la Vallée Hôpital Lariboisière Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal APHP Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7) Centre Hospitalier Régional Universitaire de Tours (CHRU Tours) CHU Caen Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN) |
format |
Article in Journal/Newspaper |
author |
Collet, Jean-Philippe Hulot, Jean-Sébastien Cuisset, Thomas Range, Grégoire Cayla, Guillaume van Belle, Éric Elhadad, Simon Rousseau, Hélène Sabouret, Pierre O'Connor, Stephen Abtan, Jérémie Kerneis, Mathieu Saint-Etienne, Christophe Barthelemy, Olivier Beygui, Farzin Silvain, Johanne Vicaut, Éric Montalescot, Gilles Investigators, Arctic |
author_facet |
Collet, Jean-Philippe Hulot, Jean-Sébastien Cuisset, Thomas Range, Grégoire Cayla, Guillaume van Belle, Éric Elhadad, Simon Rousseau, Hélène Sabouret, Pierre O'Connor, Stephen Abtan, Jérémie Kerneis, Mathieu Saint-Etienne, Christophe Barthelemy, Olivier Beygui, Farzin Silvain, Johanne Vicaut, Éric Montalescot, Gilles Investigators, Arctic |
author_sort |
Collet, Jean-Philippe |
title |
Genetic and platelet function testing of antiplatelet therapy for percutaneous coronary intervention: the ARCTIC-GENE study |
title_short |
Genetic and platelet function testing of antiplatelet therapy for percutaneous coronary intervention: the ARCTIC-GENE study |
title_full |
Genetic and platelet function testing of antiplatelet therapy for percutaneous coronary intervention: the ARCTIC-GENE study |
title_fullStr |
Genetic and platelet function testing of antiplatelet therapy for percutaneous coronary intervention: the ARCTIC-GENE study |
title_full_unstemmed |
Genetic and platelet function testing of antiplatelet therapy for percutaneous coronary intervention: the ARCTIC-GENE study |
title_sort |
genetic and platelet function testing of antiplatelet therapy for percutaneous coronary intervention: the arctic-gene study |
publisher |
HAL CCSD |
publishDate |
2015 |
url |
https://hal.science/hal-01913502 https://doi.org/10.1007/s00228-015-1917-9 |
long_lat |
ENVELOPE(156.333,156.333,-81.250,-81.250) |
geographic |
Arctic Stent |
geographic_facet |
Arctic Stent |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
ISSN: 0031-6970 EISSN: 1432-1041 European Journal of Clinical Pharmacology https://hal.science/hal-01913502 European Journal of Clinical Pharmacology, 2015, 71 (11), pp.1315 - 1324. ⟨10.1007/s00228-015-1917-9⟩ |
op_relation |
info:eu-repo/semantics/altIdentifier/doi/10.1007/s00228-015-1917-9 info:eu-repo/semantics/altIdentifier/pmid/26265231 hal-01913502 https://hal.science/hal-01913502 doi:10.1007/s00228-015-1917-9 PUBMED: 26265231 |
op_doi |
https://doi.org/10.1007/s00228-015-1917-9 |
container_title |
European Journal of Clinical Pharmacology |
container_volume |
71 |
container_issue |
11 |
container_start_page |
1315 |
op_container_end_page |
1324 |
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1802640698562838528 |
spelling |
ftunivlille:oai:HAL:hal-01913502v1 2024-06-23T07:49:58+00:00 Genetic and platelet function testing of antiplatelet therapy for percutaneous coronary intervention: the ARCTIC-GENE study Collet, Jean-Philippe Hulot, Jean-Sébastien Cuisset, Thomas Range, Grégoire Cayla, Guillaume van Belle, Éric Elhadad, Simon Rousseau, Hélène Sabouret, Pierre O'Connor, Stephen Abtan, Jérémie Kerneis, Mathieu Saint-Etienne, Christophe Barthelemy, Olivier Beygui, Farzin Silvain, Johanne Vicaut, Éric Montalescot, Gilles Investigators, Arctic Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN) Université Pierre et Marie Curie - Paris 6 (UPMC)-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) Institut de cardiologie CHU Pitié-Salpêtrière CHU Pitié-Salpêtrière 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) Département de Cardiologie Hôpital de la Timone - APHM Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Timone CHU - APHM (TIMONE) Hôpitaux de Chartres Chartres Centre Hospitalier Universitaire de Nîmes (CHU Nîmes) Université de Montpellier (UM) Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 (RNMCD) Institut Pasteur de Lille Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire CHU Lille (CHRU Lille) Service de Cardiologie Centre Hospitalier Lagny-Marne la Vallée Hôpital Lariboisière Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal APHP Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7) Centre Hospitalier Régional Universitaire de Tours (CHRU Tours) CHU Caen Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN) 2015-11 https://hal.science/hal-01913502 https://doi.org/10.1007/s00228-015-1917-9 en eng HAL CCSD Springer Verlag info:eu-repo/semantics/altIdentifier/doi/10.1007/s00228-015-1917-9 info:eu-repo/semantics/altIdentifier/pmid/26265231 hal-01913502 https://hal.science/hal-01913502 doi:10.1007/s00228-015-1917-9 PUBMED: 26265231 ISSN: 0031-6970 EISSN: 1432-1041 European Journal of Clinical Pharmacology https://hal.science/hal-01913502 European Journal of Clinical Pharmacology, 2015, 71 (11), pp.1315 - 1324. ⟨10.1007/s00228-015-1917-9⟩ Antiplatelet therapy Clopidogrel Pharmacogenetic Platelet reactivity Stent thrombosis [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology info:eu-repo/semantics/article Journal articles 2015 ftunivlille https://doi.org/10.1007/s00228-015-1917-9 2024-06-03T15:10:41Z International audience 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. Article in Journal/Newspaper Arctic LillOA (HAL Lille Open Archive, Université de Lille) Arctic Stent ENVELOPE(156.333,156.333,-81.250,-81.250) European Journal of Clinical Pharmacology 71 11 1315 1324 |