- 作者：Argirios E. Tsantes ; Ignatios Ikonomidis ; Ioannis Papadakis ; Stefanos Bonovas ; Argiri Gialeraki ; Christine Kottaridi ; Elias Kyriakou ; Styliani Kokori ; Panagiota Douramani ; Petros Kopterides ; Petros Karakitsos ; John Lekakis ; Violetta Kapsimali
- 关键词：ACS ; acute coronary syndrome ; PCI ; percutaneous coronary intervention ; CYP ; cytochrome P450 ; SNP ; single-nucleotide polymorphism ; PPI ; proton pump inhibitors ; LTA ; light transmittance aggregometry ; VASP ; flow-cytometric vasodilator-stimulated phosphoprote
- 刊名：Thrombosis Research
- 出版年：2013
- 出版时间：August, 2013
- 年：2013
- 卷：132
- 期：2
- 页码：e105-e111
- 全文大小：212 K
Background
Previous studies suggested a possible negative interference of proton pump inhibitors (PPIs) on clopidogrel¡¯s antiplatelet effect because of the competitive inhibition of the CYP 2C19 isoenzyme. Moreover, carriers of the loss-of-function allele of CYP2C19 polymorphism (CYP2C19*2) display significantly lower responses to clopidogrel. In this study, we investigated the association between CYP2C19*2 genotype, PPI intake and clopidogrel resistance in patients with coronary artery disease (CAD) and their effect on clinical outcome.Methods
We recruited 95 patients with CAD receiving chronic clopidogrel therapy in combination with aspirin. Platelet reactivity was simultaneously assessed by INNOVANCE PFA-100 P2Y, ADP-induced light transmission aggregometry (LTA), flow-cytometric vasodilator-stimulated phosphoprotein (VASP)-phosphorylation assay and multiple electrode aggregometry (Multiplate). Cardiovascular outcomes were recorded during 1-year follow-up period.
Results
Only platelet reactivity assessed by measuring platelet phosphorylated-VASP demonstrated a significant higher platelet reactivity in carriers of CYP2C19*2 (p = 0.023). The other methods displayed higher - but not statistically significant - platelet reactivity in patients carrying the CYP2C19*2 variant as compared with non-carriers. Patients on PPIs demonstrated almost similar suppression of platelet reactivity in comparison with those not treated with PPIs by all platelet function assays. In logistic regression analysis none of the platelet function assays measurements were related with clinical outcomes. Similarly neither CYP2C19*2 genetic variant nor PPI treatment were associated with adverse clinical events.
Conclusions
PPI co-administration did not influence clopidogrel¡¯s antiplatelet effect on laboratory testing by all platelet function assays used. On the contrary, patients carrying CYP2C19*2 genotype had significantly higher residual platelet reactivity as estimated by VASP-phosphorylation assay.