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Is CYP2C Haplotype Relevant for Efficacy and Bleeding Risk in Clopidogrel-Treated Patients?

Lana Ganoci1,2, Jozefina Palić3, Vladimir Trkulja2

  • 1Division of Pharmacogenomics and Therapy Individualization, Department of Laboratory Diagnostics, University Hospital Centre Zagreb, 10000 Zagreb, Croatia.

Genes
|May 25, 2024
PubMed

Insights

The CYP2C19 genotype influences clopidogrel metabolism, with poor or intermediate metabolizers facing higher ischemic event risks. However, the CYP2C:TG haplotype did not significantly alter clopidogrel

Area of Science:

  • Pharmacogenomics
  • Clinical Pharmacology
  • Cardiovascular Medicine

Background:

  • Clopidogrel efficacy and safety are linked to CYP2C19 metabolism.
  • Poor (PM) and intermediate (IM) CYP2C19 metabolizers have increased ischemic event risk.
  • A novel CYP2C:TG haplotype influences CYP2C19 substrate metabolism.

Purpose of the Study:

  • To investigate the impact of the CYP2C:TG haplotype on clopidogrel efficacy and bleeding risk.
  • To analyze the association between CYP2C19 phenotypes and clinical outcomes with clopidogrel treatment.

Main Methods:

  • Adult patients (n=283) treated with clopidogrel were genotyped for CYP2C19 (*2, *17) and the CYP2C:TG haplotype.
  • Patients were classified into CYP2C19 metabolizer phenotypes (PM, IM, NM, RM, UM).
  • Clinical outcomes, including ischemic events and bleedings, were recorded over 3-6 months.

Main Results:

  • Ischemic event incidence was numerically higher in PM/IM patients (21.6%, 21.8%) compared to NM/RM/UM patients (13.2-14.8%).
  • Bleeding event incidence was numerically lower in PM/IM patients (13.1%) versus other phenotypes (16.6-20.5%).
  • The CYP2C:TG haplotype showed no significant difference in ischemic event rates (14.1% vs. 16.1%) or bleeding rates (14.9% vs. 20.1%) between carriers and non-carriers.

Conclusions:

  • CYP2C19 genotype influences clopidogrel outcomes, with PM/IM phenotypes showing trends towards higher ischemic events and lower bleeding.
  • The CYP2C:TG haplotype did not demonstrate a significant impact on clopidogrel's clinical efficacy or safety.
  • Further research may be needed to fully elucidate the role of complex genotypes in clopidogrel response.

Keywords:
CYP2C19 phenotypeCYP2C:TG haplotypebleedingclopidogrelefficacy

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