CYP2C19*2 and Other Allelic Variants Affecting Platelet Response to Clopidogrel Tested by Thrombelastography in Patients with Acute Coronary Syndrome

Abstract

Background: To investigate the contributions of CYP2C19 polymorphisms to the various clopidogrel responses tested by thrombelastography (TEG) in Chinese patients with the acute coronary syndrome (ACS). Methods: Patients were screened prospectively with ACS diagnose and were treated with clopidogrel and aspirin dual antiplatelet therapy. CYP2C19 loss of function (LOF) and gain of function (GOF) genotype, adenosine 5′-diphosphate (ADP)-channel platelet inhibition rate (PIR) tested by TEG and the occurrence of 3-month major adverse cardiovascular events and ischemic events were assessed in 116 patients. Results: High on-treatment platelet reactivity (HTPR) prevalence defined by PIR <30% by TEG in ADP-channel was 32.76% (38/116). With respect to the normal wild type, CYP2C19*2, and *3 LOF alleles, and *17 GOF alleles, patients were classified into three metabolism phenotypes: 41.38% were extensive metabolizers (EMs), 56.90% were intermediate metabolizers (IMs), and 1.72% were poor metabolizers (PMs). Of the enrolled patients, 31.47%, 5.17%, and 0.43%, respectively, were carriers of *2, *3, and *17 alleles. The HTPR incidence differed significantly according to CYP2C19 genotypes, accounting for 18.75%, 41.54%, and 100.00% in EMs, IMs, and PMs, respectively. Eighteen (17.24%) ischemic events occurred during the 3-month follow-up, and there was a significant difference in ischemic events between HTPR group and nonhigh on-treatment platelet reactivity group. Conclusions: Genetic CYP2C19 polymorphisms are relative to the inferior, the antiplatelet activity after clopidogrel admission and may increase the incidence of ischemic events in patients with ACS.

Keywords

• Acute Coronary Syndrome; Clopidogrel Resistance; CYP2C19 Polymorphisms; Platelet Reactivity; Thrombelastography