The relationship between on-clopidogrel platelet reactivity, genotype, and post-percutaneous coronary intervention outcomes in Chinese patients

Abstract

Background. High on-clopidogrel platelet reactivity reflects a poor response to clopidogrel and is associated with ischemic events, which has been attributed to several factors such as demographic, clinical characteristics and a polymorphism of CYP2C19. Some new platelet assays monitoring on-clopidogrel platelet reactivity are currently available in China, but their relevance to the CYP2C19 genotype and post-percutaneous coronary intervention outcomes remain to be elucidated. Methods. Patients were prospectively included if they had a successful percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) and received clopidogrel and aspirin. CYP2C19 loss-of function genotype, adenosine diphosphate (ADP)-induced maximum platelet aggregation rate (MPAADP) measured by light transmittance aggregometry, ADP-induced platelet-fibrin clot strength (MAADP) measured by thrombelastography, platelet reactivity index (PRI) measured by vasodilator-stimulated phosphoprotein phosphorylation (VASP), and the occurrence of 6-month major adverse cardiovascular events (MACE) were assessed in 178 patients. Results. High on-treatment platelet reactivity prevalence defined by MPAADP > 46.0%, MAADP > 47 mm and PRI > 50.0% was 27.0%, 24.2%, and 61.2%, respectively. ADP-specific assays (VASP PRI) differed according to CYP2C19 genotype, with a significant gene–dose effect (PMs > IMs > EMs, p < 0.05). Multivariate analysis showed MPAADP > 46.0% and MAADP > 47 mm to be independent predictors of MACE at 6 months. Conclusions. CYP2C19 loss-of function genotypes with the *2 and/or *3 allele are highly prevalent in the Chinese population and are associated with higher residual platelet reactivity. High on-treatment platelet reactivity defined by MPAADP or MAADP predicts an increased risk of MACE for ACS patients undergoing PCI.