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 (MPA_ADP) measured by light transmittance aggregometry, ADP-induced platelet-fibrin clot strength (MA_ADP) 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 MPA_ADP > 46.0%, MA_ADP > 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 MPA_ADP > 46.0% and MA_ADP > 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 MPA_ADP or MA_ADP predicts an increased risk of MACE for ACS patients undergoing PCI.

Key Words::

• Acute coronary syndrome
• clopidogrel
• CYP2C19
• platelet function assay

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

This study was supported by grants (2014CFB465) from Natural Science Foundation of Hubei Province, China.