Impact of the proton pump inhibitors and CYP2C19*2 polymorphism on platelet response to clopidogrel as assessed by four platelet function assays |
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| Authors: | 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 |
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| Affiliation: | 1. Laboratory of Haematology and Blood Bank Unit, “Attiko” University Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens - Greece;2. Second Cardiology Department, “Attiko” University Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece;3. Department of Pharmacology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece;4. Department of Diagnostic Cytopathology, “Attiko” University Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece;5. Second Department of Critical Care Medicine, “Attiko” University Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece;6. Department of Microbiology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece |
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| Abstract: | BackgroundPrevious 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.MethodsWe 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.ResultsOnly 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.ConclusionsPPI 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. |
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| Keywords: | 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 phosphoprotein MEA, multiple electrode aggregometry CAD, coronary artery disease PFA, platelet function analyzer STEMI, ST-elevation myocardial infarction PRP, platelet-rich plasma PPP, platelet-poor plasma CT, closure time AUC, area under the curve PRI, platelet reactivity index RT-PCR, Real-time polymerase chain reaction |
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