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Aspirin & clopidogrel non-responsiveness & its association with genetic polymorphisms in patients with myocardial

Chandra Prakash Pandey1, Ankita Misra2, Mahendra Pal Singh Negi3

  • 1Divisions of Pharmacology, CSIR-Central Drug Research Institute; Department of Cardiology, King George Medical University, Lucknow, India.

The Indian Journal of Medical Research
|October 2, 2019
PubMed

Insights

Genetic polymorphisms in CYP2C19*2 and GPVI are linked to dual antiplatelet therapy non-responsiveness in myocardial infarction patients. This finding highlights the role of genetic factors in DAPT efficacy.

Area of Science:

  • Pharmacogenomics
  • Cardiovascular Medicine
  • Clinical Chemistry

Background:

  • Dual antiplatelet therapy (DAPT) with aspirin and clopidogrel is standard for myocardial infarction (MI) patients.
  • Patient response to DAPT can be influenced by genetic variations in key drug-metabolizing enzymes and platelet receptors.
  • Identifying non-responsiveness is crucial for optimizing treatment and preventing adverse cardiovascular events.

Purpose of the Study:

  • To investigate the association between specific gene polymorphisms and DAPT non-responsiveness in patients with MI.
  • To identify clinical and genetic factors contributing to non-response to aspirin and clopidogrel therapy.

Main Methods:

  • Light transmittance aggregometry was used to assess DAPT non-responsiveness in 207 MI patients.
  • Plasma levels of thromboxane B2 (TxB2) and soluble CD40 ligand (sCD40L) were measured.
  • CYP450, P2Y12, COX1, and GPVI gene polymorphisms were analyzed using DNA sequencing.

Main Results:

  • DAPT non-responsiveness was observed in 15.5% of the patients.
  • Non-responsiveness was significantly associated with gender, higher TxB2 levels, and the CYP2C19*2 G>A and GPVI T>C polymorphisms.
  • These associations remained significant after adjusting for confounding factors.

Conclusions:

  • Specific genetic polymorphisms, namely CYP2C19*2 G>A and GPVI T>C, are significantly associated with DAPT non-responsiveness in MI patients.
  • These genetic factors may play a role in predicting treatment response.
  • Further validation in larger cohorts with clinical follow-up is warranted.
Abstract

Keywords:
Aspirinclopidogreldrug compliancemyocardial infarctionnon-respondersplatelet activationplatelet aggregationresponderssingle-nucleotide polymorphism

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