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Clopidogrel response variability: impact of genetic polymorphism and platelet biomarkers for predicting adverse

Elena Z Golukhova1, Mariya N Ryabinina, Naida I Bulaeva

  • 11Bakoulev Center for Cardiovascular Surgery, Department of Nonivasive Cardiology, Moscow, Russia; and 2HeartDrug™ Research Laboratories, Johns Hopkins University, Towson, MD.

American Journal of Therapeutics
|May 7, 2015
PubMed

Insights

Genetic variations in CYP2C19*2 influence platelet reactivity in patients undergoing percutaneous coronary intervention (PCI). Higher reactivity in certain genotypes correlates with increased risk of adverse cardiac events after dual antiplatelet therapy.

Area of Science:

  • Cardiovascular Medicine
  • Pharmacogenomics
  • Interventional Cardiology

Background:

  • Dual antiplatelet therapy (DAPT) is crucial after percutaneous coronary intervention (PCI) for coronary artery disease (CAD).
  • CYP2C19 genetic variations significantly impact clopidogrel metabolism and efficacy.
  • Assessing platelet reactivity is vital for managing DAPT response and preventing adverse events.

Purpose of the Study:

  • To investigate the relationship between CYP2C19*2 and CYP2C19*3 genotypes and platelet reactivity.
  • To determine the association between genetic profiles, platelet function, and adverse vascular outcomes post-PCI.
  • To evaluate the utility of pharmacogenetic testing in tailoring DAPT strategies.

Main Methods:

  • Study included 55 CAD patients undergoing PCI, assessed serially pre- and post-procedure.
  • Platelet reactivity measured using light transmission aggregometry, VerifyNow Analyzer, and thromboelastography with platelet mapping.
  • Genotyping for CYP2C19*2 and CYP2C19*3 performed via allele-specific real-time polymerase chain reaction.

Main Results:

  • Higher platelet reactivity observed in patients with heterozygous (GA) and homozygous (AA) CYP2C19*2 polymorphisms compared to the common GG genotype.
  • Significant correlation found between GG, GA, and AA genotypes and platelet aggregation levels (P=0.02).
  • High platelet reactivity strongly linked to adverse vascular events (P=0.002); genotype and VerifyNow readings showed a trend (P=0.057), with cumulative impact on events being significant (P=0.041).

Conclusions:

  • CYP2C19*2 genotype variations are associated with increased platelet reactivity in CAD patients post-PCI.
  • Elevated platelet reactivity in specific genotypes may predict clopidogrel response variability and higher risk of adverse cardiac events.
  • Pharmacogenetic stratification based on CYP2C19*2 may optimize DAPT and improve clinical outcomes.

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