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CYP2C19 polymorphisms and coronary heart disease risk factors synergistically impact clopidogrel response variety

Tao Liu1, Tao Yin, Yan Li

  • 1Departments of aCardiology bRespiratory Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, China.

Coronary Artery Disease
|March 11, 2014
PubMed

Insights

Clopidogrel resistance, common in Chinese patients after PCI, is linked to CYP2C19 gene variations and risk factors like BMI and diabetes. Understanding these factors improves antiplatelet therapy effectiveness and reduces cardiovascular events.

Area of Science:

  • Pharmacogenomics
  • Cardiovascular Medicine
  • Clinical Chemistry

Background:

  • Clopidogrel's antiplatelet efficacy varies significantly among individuals.
  • Elevated platelet activity post-percutaneous coronary intervention (PCI) increases major adverse cardiovascular events.
  • CYP2C19 loss-of-function (LOF) alleles and coronary heart disease (CAD) risk factors are associated with reduced clopidogrel response.

Purpose of the Study:

  • To investigate the impact of CYP2C19 genetic variations and CAD risk factors on clopidogrel response in Chinese patients with stable CAD undergoing PCI.
  • To identify specific genetic polymorphisms and clinical factors contributing to variable clopidogrel responsiveness.

Main Methods:

  • Platelet reactivity index (PRI) measured using the vasodilator-stimulated phosphoprotein assay in 145 patients post-PCI.
  • CYP2C19 gene polymorphisms analyzed via gene chip hybrid tests.
  • Patients categorized by CYP2C19 metabolism phenotypes (extensive, intermediate, poor).

Main Results:

  • 20.67% of patients exhibited clopidogrel resistance (PRI cutoff 50%).
  • Poor metabolizers (PMs) showed significantly higher PRI compared to extensive or intermediate metabolizers (P<0.05).
  • Carriers of two CYP2C19 LOF alleles, high BMI, and type 2 diabetes were independent risk factors for clopidogrel resistance.

Conclusions:

  • CYP2C19 genetic polymorphisms, type 2 diabetes, and BMI synergistically influence clopidogrel's antiplatelet activity.
  • These factors contribute to the occurrence of major adverse cardiovascular events after PCI.
  • Personalized antiplatelet therapy strategies considering genetic and clinical factors are crucial.
Abstract

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