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Influence of CYP2C19 polymorphisms on platelet reactivity and clinical outcomes in ischemic stroke patients treated

Li-Na Qiu1, Yan Sun2, Lin Wang3

  • 1Department of Neurology, the Second Hospital of Tianjin Medical University, Tianjin 300211, China.

European Journal of Pharmacology
|December 10, 2014
PubMed

Insights

CYP2C19 genetic variations impact clopidogrel effectiveness in stroke patients. Carriers of loss-of-function alleles show altered platelet function and poorer prognosis, highlighting the need for personalized treatment strategies.

Area of Science:

  • Pharmacogenomics
  • Cardiovascular Medicine
  • Neurology

Background:

  • CYP2C19 genetic polymorphisms are known to affect clopidogrel response in cardiovascular disease.
  • Limited data exist on the impact of CYP2C19 polymorphisms in ischemic stroke patients treated with clopidogrel.
  • Understanding this relationship is crucial for optimizing antiplatelet therapy in stroke survivors.

Purpose of the Study:

  • To investigate the influence of CYP2C19 polymorphisms on platelet reactivity.
  • To evaluate the association between CYP2C19 genotype and clinical outcomes in ischemic stroke patients receiving clopidogrel.
  • To determine if CYP2C19 carriage predicts prognosis in this patient group.

Main Methods:

  • A cohort of 211 ischemic stroke patients treated with clopidogrel underwent CYP2C19 genotyping.
  • Platelet function was assessed using flow cytometry, measuring adenosine diphosphate-induced platelet aggregation (ADP-PAg) and activation markers (PAC-1, CD62P, CD63).
  • Clinical outcomes, including prognosis (modified Rankin Scale) and ischemic events, were evaluated at 6-month follow-up.

Main Results:

  • 61.1% of patients carried CYP2C19 loss-of-function (LOF) alleles (*2, *3).
  • CYP2C19 LOF allele carriers exhibited higher residual platelet reactivity (increased ADP-PAg, PAC-1, CD62P, CD63) after clopidogrel therapy.
  • Carriers had a significantly poorer prognosis (P=0.025) and CYP2C19 carriage was an independent predictor of poor prognosis (OR, 3.01; P=0.016), though not associated with ischemic events.

Conclusions:

  • CYP2C19 LOF allele carriage significantly impacts clopidogrel response, leading to increased platelet reactivity in ischemic stroke patients.
  • CYP2C19 genotype is a significant predictor of poor prognosis in ischemic stroke patients treated with clopidogrel.
  • These findings underscore the importance of pharmacogenetic testing for personalized clopidogrel therapy in stroke management.

Keywords:
Adenosine diphosphate (PubChem CID: 6022)CYP2C19ClopidogrelClopidogrel (PubChem CID: 60606)Flow cytometryGenetic polymorphismIschemic strokePlatelet function tests

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