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The relationship between on-clopidogrel platelet reactivity, genotype, and post-percutaneous coronary intervention

Ning Tang1, Shiyu Yin, Ziyong Sun

  • 1Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, Hubei 430030 , China.

Scandinavian Journal of Clinical and Laboratory Investigation
|January 17, 2015
PubMed

Insights

High on-clopidogrel platelet reactivity, linked to CYP2C19 genotype, increases ischemic event risk in patients after percutaneous coronary intervention. Specific assays can predict major adverse cardiovascular events.

Area of Science:

  • Cardiology
  • Pharmacogenomics
  • Clinical Chemistry

Background:

  • High on-clopidogrel platelet reactivity is a known risk factor for ischemic events.
  • Factors influencing this include demographics, clinical characteristics, and CYP2C19 gene variations.
  • The clinical relevance of new platelet assays and their association with CYP2C19 genotype and outcomes in China requires investigation.

Purpose of the Study:

  • To evaluate the relationship between CYP2C19 genotype and platelet reactivity in Chinese patients undergoing percutaneous coronary intervention (PCI).
  • To assess the predictive value of different platelet function assays for major adverse cardiovascular events (MACE) post-PCI.

Main Methods:

  • Prospective study of 178 patients with acute coronary syndrome (ACS) who underwent successful PCI and received clopidogrel and aspirin.
  • Assessed CYP2C19 loss-of-function genotype, adenosine diphosphate (ADP)-induced maximum platelet aggregation rate (MPA ADP), ADP-induced platelet-fibrin clot strength (MA ADP), and vasodilator-stimulated phosphoprotein phosphorylation (VASP) platelet reactivity index (PRI).
  • Monitored for 6-month MACE.

Main Results:

  • Prevalence of high on-treatment platelet reactivity varied by assay: MPA ADP (27.0%), MA ADP (24.2%), and VASP PRI (61.2%).
  • VASP PRI showed significant differences based on CYP2C19 genotype (PMs > IMs > EMs).
  • Multivariate analysis identified MPA ADP > 46.0% and MA ADP > 47 mm as independent predictors of 6-month MACE.

Conclusions:

  • CYP2C19 loss-of-function genotypes (*2 and/or *3 alleles) are common in the Chinese population and correlate with increased residual platelet reactivity.
  • High on-treatment platelet reactivity, as measured by MPA ADP or MA ADP, predicts a higher risk of MACE in ACS patients post-PCI.
Abstract

Keywords:
Acute coronary syndromeCYP2C19clopidogrelplatelet function assay

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