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

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.

• Authors: Martha Eva Viveros, Carlos Areán, Sergio Gutiérrez, Soledad Vázquez, Mario Humberto Cardiel, Alejandra Taboada, Gissela Marín, Ruben Solorio, Nalley García
• Journal: Archivos de cardiologia de Mexico (Arch Cardiol Mex) 2016 Oct - Dec Vol. 86 Issue 4 Pg. 297-304 ISSN: 1665-1731 [Electronic] Mexico
• PMID: 26971130 (Publication Type: Journal Article)
• Copyright: Copyright © 2016 Instituto Nacional de Cardiología Ignacio Chávez. Publicado por Masson Doyma México S.A. All rights reserved.

Chemical References

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

Topics

• 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, therapeutic use)