Abstract 15054: Impact of CYP2C19 Polymorphism and Diabetes Mellitus on Platelet Reactivity and Clinical Outcomes in Patients Following Coronary Stent Placement
Background: CYP2C19 polymorphism and diabetes mellitus (DM) is associated with the reduced effect on platelet response to clopidogrel. However, it remains unknown about the relation between CYP2C19 genotype and diabetes to clinical events after coronary stenting. The aim was to examine the impact of CYP2C19 polymorphism and diabetes on platelet reactivity and clinical outcomes in patients following coronary stent placement.
Methods: Adenosine diphosphate induced platelet aggregation using light transmission aggregometer was measured as response to clopidogrel in 191 patients (male 66%, age 69 years) treated with stent placement for coronary artery disease (CAD). CYP2C19 polymorphism was also examined, and classified into three phenotypes: (1) extensive metabolizer (EM) carrying normal function (wild-type) alleles (CYP2C19*1/*1), (2) intermediate metabolizer (IM) carrying one loss-of-function allele (*1/*2, *1/*3), and (3) poor metabolizer (PM) carrying two loss-of-function alleles (*2/*2, *2/*3, *3/*3).
Results: Patients were divided into two groups; DM (n=85), and non-DM (n=106). The values of residual platelet reactivity were 3935+/-1513, and 4199+/-1673 AU*min in DM, and non-DM group, respectively. In contrast to distribution of CYP2C19 polymorphism in Caucasians, the ratio of CYP2C19 loss-of-function allele was higher in Japanese (EM, 34%; IM, 47%; PM, 19%). According to CYP2C19 genotype, the levels of residual platelet reactivity in EM, IM, and PM were 3822, 3643, and 4713 AU*min in DM group, and 3639, 4243, and 5551 in non-DM, respectively. Although there was no difference in platelet reactivity of EM between DM and non-DM, platelet reactivity was higher in IM and PM of non-DM group than in IM and PM of DM. As to clinical outcomes, there were no differences in cardiovascular events (death, myocardial infarction, stroke, unstable angina) among CYP2C19 genotypes in DM group. Whereas, in non-DM group, cardiovascular events were more increased in patients carrying at least one loss-of-function allele (*2 or *3) than in patients with CYP2C19 wild-type homozygotes (*1/*1).
Conclusions: In patients with CAD, impact of CYP2C19 loss-of-function polymorphism on clinical outcomes is more powerful in non-DM compared with DM patients.
- © 2011 by American Heart Association, Inc.