AIMS: To investigate an association of responsiveness to clopidogrel loading dose with genotypes of cytochrome P450 (CYP) 2C19, other CYP isozymes and nongenetic factors in patients with coronary artery disease. MATERIALS & METHODS: Genotyping for CYP2C19 (*2, *3 and *17), CYP3A4*1B and CYP3A5*3 variants was performed in patients (n = 237) who underwent percutaneous coronary intervention. Adenosine diphosphate-induced platelet aggregation was determined after first administration of 600 mg clopidogrel. RESULTS: CYP2C19*2 carriers showed significantly increased residual platelet aggregation (RPA) (OR: 4.6; 95% CI: 2.5-8.7; p < 0.0001) compared with noncarriers. All other polymorphisms had no influence on RPA. For the development of a risk score for better prediction of RPA, CYP2C19*2 genotype and previously identified nongenetic risk factors (age >65 years, Type 2 diabetes mellitus, decreased left ventricular function, renal failure and acute coronary syndrome) were analyzed. Multivariable logistic regression analysis showed a significant correlation of the nongenetic factors (chi (2) = 5.32; p = 0.021) and CYP2C19*2 (chi (2) = 21.31; p < 0.0001) with high RPA, and an even higher association for the combination of both (chi (2) = 25.85; p < 0.0001). CONCLUSIONS: Prediction of responsiveness after clopidogrel loading dose may substantially be improved by adding CYP2C19*2 genotype to nongenetic risk factors.
AIMS: To investigate an association of responsiveness to clopidogrel loading dose with genotypes of cytochrome P450 (CYP) 2C19, other CYP isozymes and nongenetic factors in patients with coronary artery disease. MATERIALS & METHODS: Genotyping for CYP2C19 (*2, *3 and *17), CYP3A4*1B and CYP3A5*3 variants was performed in patients (n = 237) who underwent percutaneous coronary intervention. Adenosine diphosphate-induced platelet aggregation was determined after first administration of 600 mg clopidogrel. RESULTS:CYP2C19*2 carriers showed significantly increased residual platelet aggregation (RPA) (OR: 4.6; 95% CI: 2.5-8.7; p < 0.0001) compared with noncarriers. All other polymorphisms had no influence on RPA. For the development of a risk score for better prediction of RPA, CYP2C19*2 genotype and previously identified nongenetic risk factors (age >65 years, Type 2 diabetes mellitus, decreased left ventricular function, renal failure and acute coronary syndrome) were analyzed. Multivariable logistic regression analysis showed a significant correlation of the nongenetic factors (chi (2) = 5.32; p = 0.021) and CYP2C19*2 (chi (2) = 21.31; p < 0.0001) with high RPA, and an even higher association for the combination of both (chi (2) = 25.85; p < 0.0001). CONCLUSIONS: Prediction of responsiveness after clopidogrel loading dose may substantially be improved by adding CYP2C19*2 genotype to nongenetic risk factors.
Authors: Thomas O Bergmeijer; Jean-Luc Reny; Ruth E Pakyz; Li Gong; Joshua P Lewis; Eun-Young Kim; Daniel Aradi; Israel Fernandez-Cadenas; Richard B Horenstein; Ming Ta Michael Lee; Ryan M Whaley; Joan Montaner; Gian Franco Gensini; John H Cleator; Kiyuk Chang; Lene Holmvang; Willibald Hochholzer; Dan M Roden; Stefan Winter; Russ B Altman; Dimitrios Alexopoulos; Ho-Sook Kim; Jean-Pierre Déry; Meinrad Gawaz; Kevin Bliden; Marco Valgimigli; Rossella Marcucci; Gianluca Campo; Elke Schaeffeler; Nadia P Dridi; Ming-Shien Wen; Jae Gook Shin; Tabassome Simon; Pierre Fontana; Betti Giusti; Tobias Geisler; Michiaki Kubo; Dietmar Trenk; Jolanta M Siller-Matula; Jurriën M Ten Berg; Paul A Gurbel; Jean-Sebastien Hulot; Braxton D Mitchell; Matthias Schwab; Marylyn DeRiggi Ritchie; Teri E Klein; Alan R Shuldiner Journal: Am Heart J Date: 2017-12-17 Impact factor: 4.749