Abstract 13827: The Influence of Cytochrome 2c19 Allelic Variants on Clopidogrel-Mediated Platelet Inhibition Evaluated by Five Different Platelet Function Tests
Objectives: The antiplatelet effect of clopidogrel has recently been linked to cytochrome P450 (CYP) 2C19 carrier status. In order to study the impact of CYP2C19 allelic variants on clopidogrel-mediated platelet inhibition and to define the test correlating best with the patients′ genotype, we studied genetic variants and five different platelet function tests in 156 patients after angioplasty and stenting for cardiovascular disease.
Methods: Platelet reactivity was assessed by light transmission aggregometry (LTA), the VerifyNow P2Y12 assay, the vasodilator-stimulated phosphoprotein (VASP) phosphorylation assay, multiple electrode aggregometry (MEA), and the Impact-R. Allelic variants of CYP2C19 were determined with the Infiniti® CYP450 2C19+ assay.
Results: CYP2C19 *2 carriers (wt/*2, *2/*2, n=35) showed a significantly higher platelet reactivity compared to a combined low-risk genotype of wildtype and *17 carriers (wt/*17, *17/*17, n=46) by the VASP assay (table, P<0.05). Further, significantly more patients with high on-treatment residual platelet reactivity (n=39) identified by the VASP assay were found among CYP2C19 *2 carriers (n=19, 35.8%) than non-carriers (n=20, 19.4% P=0.03). For each ten unit increase of the VASP platelet reactivity index, the risk of having a CYP2C19 *2 allele increased by 22%. No significant associations were observed between CYP2C19 *2 carrier status and any other platelet function test. Patients with CYP2C19 *17 allelic variants showed no significantly lower values in any test system compared to wildtype.
Conclusions: Patients with the CYP2C19 *2 allelic variant show significantly higher platelet activation in the VASP assay. Clopidogrel non-responders identified by VASP might be candidates for further genetic testing.
- © 2010 by American Heart Association, Inc.