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Genetic determinant of on-treatment reactivity identified in patients treated with clopidogrel after PCI
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Genotype CYP2C19 may be a key genetic determinant of on-treatment reactivity of clopidogrel both early and late after percutaneous coronary intervention, according to new research published in the Journal of the American College of Cardiology.
In a prespecified genetic substudy of the GRAVITAS trial, researchers examined the influence of single nucleotide polymorphisms (SNPs) on the pharmacodynamic effect of high- or standard-dose clopidogrel (Plavix, Bristol-Myers Squibb/Sanofi Pharmaceuticals Partnership) after PCI. DNA samples of 1,028 patients were included in the analysis of on-treatment reactivity at 12 to 24 hours after PCI. Data was available for 702 patients at 30 days and 672 patients at 6 months. The associations between candidate SNPs and on-treatment reactivity were examined using linear regression.
CYP2C19 was found to be significantly associated with on-treatment reactivity at 12 to 24 hours, 30 days and 6 months after PCI. Other SNPs examined were not.
“CYP2C19, but not PON1 or ABCB1, is a significant determinant of the pharmacodynamic effects of clopidogrel, both early and late after PCI. In patients with high [on-treatment reactivity] identified by platelet function testing, the CYP2C19 genotype provides limited incremental information regarding the risk of persistently high reactivity with clopidogrel 150-mg maintenance dosing,” Matthew J. Price, MD, director, Cardiac Catheterization Laboratory, Scripps Clinic, La Jolla, Calif., and colleagues said in the study’s abstract conclusion.
Disclosure: This study was funded through an investigator-initiated grant from Bristol-Myers Squibb/Sanofi-Aventis. See the study for a full list of researcher disclosures.
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