BACKGROUND: Prognostic values of genotyping and phenotyping for assessment of clopidogrel responsiveness have been shown in independent studies. OBJECTIVES: To compare different assays for prediction of events during long-term follow-up. METHODS: In this prospective cohort study polymorphisms of CYP2C19*2 and CYP2C19*17 alleles, vasodilator-stimulated phosphoprotein phosphorylation (VASP) assay, multiple electrode aggregometry (MEA), cone and platelet analyser (CPA) and platelet function analyser (PFA-100) were performed in 416 patients undergoing percutaneous coronary intervention. The rates of events were recorded during a 12-month follow-up. RESULTS: Platelet aggregation by MEA predicted stent thrombosis (2.4%) better (c-index = 0.90; P < 0.001; sensitivity = 90%; specificity = 83%) than the VASP assay, CPA or PFA-100 (c-index < 0.70; P > 0.05; sensitivity < 70%; specificity < 70% for all) or even the CYP2C19*2 polymorphism (c-index < 0.56; P > 0.05; sensitivity = 30%; specificity = 71%). Survival analysis indicated that patients classified as poor responders by MEA had a substantially higher risk of developing stent thrombosis or MACE than clopidogrel responders (12.5% vs. 0.3%, P < 0.001, and 18.5% vs. 11.3%, P = 0.022, respectively), whereas poor metabolizers (CYP2C19*1/*2 or *2/*2 carriers) were not at increased risks (stent thrombosis, 2.7% vs. 2.5%, P > 0.05; MACE, 13.5% vs. 12.1%, P = 0.556). The incidence of major bleedings (2.6%) was numerically higher in patients with an enhanced vs. poor response to clopidogrel assessed by MEA (4% vs. 0%) or in ultra-metabolizers vs. regular metabolizers (CYP2C19*17/*17 vs. CYP2C19*1/*1; 9.5% vs. 2%). The classification tree analysis demonstrated that acute coronary syndrome at hospitalization and diabetes mellitus were the best discriminators for clopidogrel responder status. CONCLUSIONS: Phenotyping of platelet response to clopidogrel was a better predictor of stent thrombosis than genotyping.
BACKGROUND: Prognostic values of genotyping and phenotyping for assessment of clopidogrel responsiveness have been shown in independent studies. OBJECTIVES: To compare different assays for prediction of events during long-term follow-up. METHODS: In this prospective cohort study polymorphisms of CYP2C19*2 and CYP2C19*17 alleles, vasodilator-stimulated phosphoprotein phosphorylation (VASP) assay, multiple electrode aggregometry (MEA), cone and platelet analyser (CPA) and platelet function analyser (PFA-100) were performed in 416 patients undergoing percutaneous coronary intervention. The rates of events were recorded during a 12-month follow-up. RESULTS: Platelet aggregation by MEA predicted stent thrombosis (2.4%) better (c-index = 0.90; P < 0.001; sensitivity = 90%; specificity = 83%) than the VASP assay, CPA or PFA-100 (c-index < 0.70; P > 0.05; sensitivity < 70%; specificity < 70% for all) or even the CYP2C19*2 polymorphism (c-index < 0.56; P > 0.05; sensitivity = 30%; specificity = 71%). Survival analysis indicated that patients classified as poor responders by MEA had a substantially higher risk of developing stent thrombosis or MACE than clopidogrel responders (12.5% vs. 0.3%, P < 0.001, and 18.5% vs. 11.3%, P = 0.022, respectively), whereas poor metabolizers (CYP2C19*1/*2 or *2/*2 carriers) were not at increased risks (stent thrombosis, 2.7% vs. 2.5%, P > 0.05; MACE, 13.5% vs. 12.1%, P = 0.556). The incidence of major bleedings (2.6%) was numerically higher in patients with an enhanced vs. poor response to clopidogrel assessed by MEA (4% vs. 0%) or in ultra-metabolizers vs. regular metabolizers (CYP2C19*17/*17 vs. CYP2C19*1/*1; 9.5% vs. 2%). The classification tree analysis demonstrated that acute coronary syndrome at hospitalization and diabetes mellitus were the best discriminators for clopidogrel responder status. CONCLUSIONS: Phenotyping of platelet response to clopidogrel was a better predictor of stent thrombosis than genotyping.
Authors: Francesca Wirth; Graziella Zahra; Robert G Xuereb; Christopher Barbara; Albert Fenech; Lilian M Azzopardi Journal: Int J Clin Pharm Date: 2016-03-15
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Authors: Melissa Mejin; Wen Ni Tiong; Lana Yin Hui Lai; Lee Len Tiong; Adam Mohamad Bujang; Siaw San Hwang; Tiong Kiam Ong; Alan Yean Yip Fong Journal: Int J Clin Pharm Date: 2013-05-10
Authors: Michal Droppa; Dimitri Tschernow; Karin A L Müller; Elli Tavlaki; Athanasios Karathanos; Fabian Stimpfle; Elke Schaeffeler; Matthias Schwab; Alexander Tolios; Jolanta M Siller-Matula; Meinrad Gawaz; Tobias Geisler Journal: PLoS One Date: 2015-03-23 Impact factor: 3.240
Authors: Jolanta M Siller-Matula; Irene M Lang; Thomas Neunteufl; Marek Kozinski; Gerald Maurer; Katarzyna Linkowska; Tomasz Grzybowski; Jacek Kubica; Bernd Jilma Journal: PLoS One Date: 2014-07-22 Impact factor: 3.240