Evaluation of clopidogrel response variability and identification of the CYP2C19 polymorphism in Mexican patients

Arch Cardiol Mex. Oct-Dec 2016;86(4):297-304. doi: 10.1016/j.acmx.2016.01.007. Epub 2016 Mar 9.

Abstract

Objective: Drug inhibition of platelet P2Y12 adenosine diphosphate receptor has reduced the incidence of adverse cardiovascular events after percutaneous coronary interventions. The analysis of the phosphorylation status of vasodilator-stimulated phosphoprotein by flow cytometry has shown a predictive value for adverse events and stent thrombosis. Polymorphisms of CYP2C19 in high risk patients may also relate to adverse cardiovascular events.

Methods: Ninety patients were enrolled. Patients received a 600mg clopidogrel loading dose. Blood samples were obtained at the time of the procedure and 24h later, platelet reactivity was assessed by vasodilator-stimulated phosphoprotein phosphorylation measurement using flow cytometry. Low response to clopidogrel was defined as a platelet reactivity index≥50%. The presence of CYP2C19*2 was identified with the restriction enzyme SmaI.

Results: Mean platelet reactivity index: 53.45±22.48% in the baseline sample and 57.14±23.08% at 24h (p=0.183); 40% of patients behaved as good responders, the rest behaved as non-responders with 38% of patients showing platelet reactivity indexes between 50-70% and 22% showing indexes above 70%. The CYP2C19*2 polymorphism was found in 17% of patients, with a 3.9% AA homozygous genotype carriers.

Conclusion: Response to the clopidogrel loading dose showed a wide variability among patients with 40% responding to the drug according to previously established cut-off values. Our results showed that 3.9% of patients show the AA genotype. To our knowledge, this is the first study involving clopidogrel response by flow citometry and genotype typification in Mexican Mestizo population.

Keywords: Alta reactividad plaquetaria en tratamiento; Análisis VASP; CYP2C19*2 polymorphysm; Clopidogrel resistance; High on treatment platelet reactivity; Mexico; México; P2Y12; Polimorfismo CYP2C19*2; Receptor P2Y12; Resistencia a clopidogrel; VASP analysis.

MeSH terms

  • Clopidogrel
  • Cross-Sectional Studies
  • Cytochrome P-450 CYP2C19 / genetics*
  • Female
  • Humans
  • Male
  • Mexico
  • Middle Aged
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Polymorphism, Genetic*
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / therapeutic use

Substances

  • Platelet Aggregation Inhibitors
  • Clopidogrel
  • Cytochrome P-450 CYP2C19
  • Ticlopidine