Jean-Sébastien Hulot1, Bernard Chevalier2, Loic Belle3, Guillaume Cayla4, Khalife Khalife5, François Funck6, Romain Berthier7, Christophe Piot8, Muriel Tafflet9, Gilles Montalescot10. 1. Université de Paris, CIC1418 et DMU CARTE, Assistance Publique Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France. Electronic address: jean-sebastien.hulot@aphp.fr. 2. Ramsay Générale de Santé, ICPS, Massy, France. 3. Centre Hospitalier de la Région Annecienne, Annecy, France. 4. Service de Cardiologie CHU Nîmes, Université Montpellier, Montpellier, France. 5. Hôpital du Bon Secours, Metz, France. 6. Centre Hospitalier René Dubos, Pontoise, France. 7. Centre Hospitalier Sud Francilien, Corbeil-Essonnes, France. 8. Hôpital Arnaud de Villeneuve, Montpellier, France. 9. Université de Paris, Paris Cardiovascular Research Center PARCC, INSERM, Paris, France. 10. Sorbonne Université-Université Paris 6, ACTION Study Group, Groupe Hospitalier Pitié-Salpêtrière (Assistance Publique Hôpitaux de Paris), INSERM UMRS 1166, Paris, France.
Abstract
OBJECTIVES: The aim of this study was to evaluate prospectively the clinical impact of routine transmission of CYP2C19 genotype in the management of acute ST-segment elevation myocardial infarction with primary percutaneous coronary intervention. BACKGROUND: Response to clopidogrel differs widely among patients, notably because of CYP2C19 genetic polymorphisms. METHODS: CYP2C19 genotype (6 alleles) was determined centrally and communicated within 4.1 ± 1.9 days of primary percutaneous coronary intervention in 1,445 patients with ST-segment elevation myocardial infarction recruited at 57 centers in France. CYP2C19 metabolic status was predicted from genotype and served to adjust thienopyridine treatment. The primary endpoint was differences in 12-month outcomes (death, myocardial infarction, and stent thrombosis) between patients with the wild-type genotype or gain-of-function allele (class 1, n = 1,118) and those with loss-of-function (LOF) alleles (class 2, n = 272) who received optimized thienopyridine treatment. RESULTS: Detection of LOF alleles resulted in adjustment of P2Y12 inhibition in 85% of patients, with significantly higher use of prasugrel or double-dose clopidogrel. The primary endpoint did not differ between class 1 and class 2 patients (3.31% vs. 3.04%, respectively; p = 0.82). In contrast, carriers of LOF alleles without treatment adjustment had significantly worse outcomes (15.6%; p < 0.05). Bleeding rates were not different between groups. CONCLUSIONS: In a real-world setting, a complete CYPC2C19 genotype can be mostly determined in <7 days using analysis of saliva deoxyribonucleic acid collected during the in-hospital phase among patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention. Genotype information led to stronger platelet inhibition treatment in the vast majority of LOF allele carriers and to similar clinical outcomes as in patients carrying the wild-type genotype or gain-of-function allele. (Genotyping Infarct Patients to Adjust and Normalize Thienopyridine Treatment [GIANT]; NCT01134380).
OBJECTIVES: The aim of this study was to evaluate prospectively the clinical impact of routine transmission of CYP2C19 genotype in the management of acute ST-segment elevation myocardial infarction with primary percutaneous coronary intervention. BACKGROUND: Response to clopidogrel differs widely among patients, notably because of CYP2C19 genetic polymorphisms. METHODS:CYP2C19 genotype (6 alleles) was determined centrally and communicated within 4.1 ± 1.9 days of primary percutaneous coronary intervention in 1,445 patients with ST-segment elevation myocardial infarction recruited at 57 centers in France. CYP2C19 metabolic status was predicted from genotype and served to adjust thienopyridine treatment. The primary endpoint was differences in 12-month outcomes (death, myocardial infarction, and stent thrombosis) between patients with the wild-type genotype or gain-of-function allele (class 1, n = 1,118) and those with loss-of-function (LOF) alleles (class 2, n = 272) who received optimized thienopyridine treatment. RESULTS: Detection of LOF alleles resulted in adjustment of P2Y12 inhibition in 85% of patients, with significantly higher use of prasugrel or double-dose clopidogrel. The primary endpoint did not differ between class 1 and class 2 patients (3.31% vs. 3.04%, respectively; p = 0.82). In contrast, carriers of LOF alleles without treatment adjustment had significantly worse outcomes (15.6%; p < 0.05). Bleeding rates were not different between groups. CONCLUSIONS: In a real-world setting, a complete CYPC2C19 genotype can be mostly determined in <7 days using analysis of saliva deoxyribonucleic acid collected during the in-hospital phase among patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention. Genotype information led to stronger platelet inhibition treatment in the vast majority of LOF allele carriers and to similar clinical outcomes as in patients carrying the wild-type genotype or gain-of-function allele. (Genotyping InfarctPatients to Adjust and Normalize Thienopyridine Treatment [GIANT]; NCT01134380).
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