Association of CYP2C19*2 polymorphism with clopidogrel response and 1-year major adverse cardiovascular events in a multiethnic population with drug-eluting stents

Pharmacogenomics. 2017 Aug;18(13):1225-1239. doi: 10.2217/pgs-2017-0078. Epub 2017 Jul 26.

Abstract

Background: Patients undergoing elective percutaneous coronary intervention (PCI) with drug-eluting stents (DES) who have impaired clopidogrel response, have a higher risk of subsequent major adverse cardiovascular events (MACE).

Aim of the study: To establish the relationship between CYP2C19 genotype, clopidogrel responsiveness and 1-year MACE.

Materials & methods: Aspirin/clopidogrel responses were assessed with Multiplate Analyzer and CYP2C19*2 allele by SpartanRx.

Results: A total of 42.0% carried ≥1 CYP2C19*2 allele. Prevalences of aspirin and clopidogrel high on-treatment platelet reactivity (HPR; local cutoffs: 300 AU*min for aspirin and 600 AU*min for clopidogrel) were 11.5% and 19.8% respectively. In multivariate ana-lysis, clopidogrel HPR was found to be an independent predictor for 1-year MACE (adj HR: 3.48, p = 0.022 ).

Conclusion: Having clopidogrel HPR could be a potentially modifiable risk factor guided by phenotyping.

Keywords: CYP2C19*2 genetic polymorphism; double antiplatelet therapy; percutaneous coronary intervention; platelet function test.

MeSH terms

  • Alleles
  • Cardiovascular Diseases / chemically induced*
  • Cardiovascular Diseases / genetics*
  • Clopidogrel
  • Cohort Studies
  • Cytochrome P-450 CYP2C19 / genetics*
  • Drug-Eluting Stents / adverse effects
  • Drug-Related Side Effects and Adverse Reactions / genetics*
  • Female
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Platelet Aggregation Inhibitors / adverse effects*
  • Platelet Aggregation Inhibitors / therapeutic use
  • Polymorphism, Genetic / genetics*
  • Risk Factors
  • Ticlopidine / adverse effects
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / therapeutic use

Substances

  • Platelet Aggregation Inhibitors
  • Clopidogrel
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19
  • Ticlopidine