Routine CYP2C19 Genotyping to Adjust Thienopyridine Treatment After Primary PCI for STEMI

• DOI: 10.1016/j.jcin.2020.01.219
• Publication Date: 2020-03-02T20:44:34Z
• Authors: Jean-Sébastien Hulot; Bernard Chevalier; Loic Belle; Guillaume Cayla; Khalife Khalife; François Funck; Romain Berthier; Christophe Piot; Muriel Tafflet; Gilles Montalescot; Bernard Chevalier; Gilles Montalescot; Jean-Sébastien Hulot; Loïc Belle; Guillaume Cayla; Hervé Le Breton; Emmanuel Teiger; Grégoire Dambrin; K. Khalife; L. Schmutz; F. Funck; R. Berthier; C. Piot; G. Hannebicque; G. Montalescot; T. Lognone; F. De Poli; B. Chevalier; N. Lhoest; M. Schneeberger; N. Delarche; A. Faure; H. Aelion; M. Godin; M. Gilard; B. Ritz; P. Barraud; P. Barnay; L.N. Saïdi; O. Le Dref; P. Garot; G. Range; J. Georges; C. Robin; Y. Cottin; L. Belle; G. Souteyrand; A. Lafont; A. Fournier; P. Dupouy; P. Dupouy; J. Shayne; P. Chapon; C. Boureux; J.P. Faure; H. Ben Amer; A. Furber; O. Ormezzano; G. Bayet; G. Karrillon; L. Maillard; A. Grenzinger; A. Avran; R. Koning; D. Dumant; X. Lamit; R. Dauphin; L. Drogoul; T. Cuisset; O. Wittenberg; J.P. Peyre; P. Laury; R. Robert
• Keywords: Male; Polymorphism, Genetic; Pharmacogenomic Variants; Coronary Thrombosis; Clinical Decision-Making; Drug Resistance; Middle Aged; Risk Assessment; Clopidogrel; 3. Good health; Cytochrome P-450 CYP2C19; 03 medical and health sciences; Percutaneous Coronary Intervention; 0302 clinical medicine; Recurrence; Humans; Female; France; Prospective Studies; Precision Medicine; Prasugrel Hydrochloride; Platelet Aggregation Inhibitors; Aged

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.Response to clopidogrel differs widely among patients, notably because of CYP2C19 genetic polymorphisms.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.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.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).