The relation between CYP2C19 genotype and phenotype in stented patients on maintenance dual antiplatelet therapy

Paul A. Gurbel, Alan R. Shuldiner, Kevin P. Bliden, Kathaleen Ryan, Ruth E. Pakyz, Udaya S. Tantry

Research output: Contribution to journalArticle

Abstract

Both high platelet reactivity (HPR) and CYP2C19 genotyping have been proposed to stratify cardiovascular event risk and to personalize maintenance dual antiplatelet therapy (DAPT) in stented patients. However, how well CYP2C19 genotype correlates with HPR in patients on maintenance DAPT is less clear. We determined the association of CYP2C19 loss-of-function (*2) and gain-of-function (*17) allele status with platelet reactivity in 118 stented patients on DAPT ≥2 weeks and in 143 patients with stable coronary artery disease on aspirin therapy alone. Thirty-three percent and 39% carried at least 1 copy of *2 and *17 alleles, respectively. Neither allele was associated with platelet reactivity in patients on aspirin therapy alone. On DAPT, platelet aggregation was higher in those with *2 allele than noncarriers (P ≤ .01) but did not differ between those with the *17 allele and noncarriers. The prevalence of HPR using the 20 μM adenosine diphosphate-induced aggregation cutpoint was 34% in the total population: 26% in *1/*1 homozygotes, 49% in those with the *2 allele, and 20% in those with the *17 allele (P = .006). Determination of diplotype status enhanced identification of HPR. However, platelet function on DAPT is highly variable within diplotype groups. Therefore, CYP2C19 genotype and HPR are imperfect correlates of each other. Because both predict cardiovascular events with similar risk ratios, CYP2C19 genotyping and HPR may provide complementary information to stratify risk and personalized DAPT in stented patients than either alone.

Original languageEnglish (US)
Pages (from-to)598-604
Number of pages7
JournalAmerican heart journal
Volume161
Issue number3
DOIs
StatePublished - Mar 3 2011

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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    Gurbel, P. A., Shuldiner, A. R., Bliden, K. P., Ryan, K., Pakyz, R. E., & Tantry, U. S. (2011). The relation between CYP2C19 genotype and phenotype in stented patients on maintenance dual antiplatelet therapy. American heart journal, 161(3), 598-604. https://doi.org/10.1016/j.ahj.2010.12.011