Routine CYP2C19 Genotyping to Adjust Thienopyridine Treatment After Primary PCI for STEMI: Results of the GIANT Study

JACC. Cardiovascular Interventions
Jean-Sébastien HulotGIANT Investigators

Abstract

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%,...Continue Reading

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Citations

Nov 4, 2020·British Journal of Clinical Pharmacology·Hanxu ZhangYimin Cui
Mar 7, 2020·JACC. Cardiovascular Interventions·Jurriën M Ten Berg, Paul W A Janssen
May 7, 2021·Nature Reviews. Cardiology·Julio D Duarte, Larisa H Cavallari
May 10, 2020·JACC. Cardiovascular Interventions·Simone CalcagnoFrancesco Versaci
May 22, 2021·Frontiers in Cardiovascular Medicine·Hugo Ten Cate
May 18, 2021·Expert Review of Clinical Pharmacology·Mattia GalliDominick J Angiolillo
Jun 20, 2020·JACC. Cardiovascular Interventions·Jung-Joon Cha, Do-Sun Lim
Jun 20, 2020·JACC. Cardiovascular Interventions·Jean-Sébastien Hulot, Gilles Montalescot
Jun 9, 2021·Clinical Pharmacology and Therapeutics·Jasmine A LuzumLarisa H Cavallari

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