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

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

Author information

1
División de Estudios de Posgrado, Facultad de Ciencias Médicas y Biológicas Dr. Ignacio Chávez, Universidad Michoacana de San Nicolás de Hidalgo, Morelia, Michoacán, Mexico. Electronic address: marthaevaviveros@yahoo.com.mx.
2
Servicio de Cardiología Intervencionista, Hospital General Dr. Miguel Silva, Morelia, Michoacán, Mexico.
3
División de Estudios de Posgrado, Facultad de Ciencias Médicas y Biológicas Dr. Ignacio Chávez, Universidad Michoacana de San Nicolás de Hidalgo, Morelia, Michoacán, Mexico.
4
Unidad de Investigación Dr. Mario Alvizouri, Hospital General Dr. Miguel Silva, Morelia, Michoacán, Mexico.

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

PMID:
26971130
DOI:
10.1016/j.acmx.2016.01.007
[Indexed for MEDLINE]

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