Abstract 12931: Is There Difference in Impact of CYP2C19 Polymorphism on Platelet Reactivity and Cardiovascular Events Between Chronic Kidney Disease (CKD) and Non-CKD ?
Background: Japanese more often carry CYP2C19 variant than Caucasian. The difference in influence of CYP2C19 loss-of-function (LOF) alleles (*2 and *3) on clopidogrel response and clinical outcomes between CKD and non-CKD has not been reported. The aim was to examine the difference in impact of CYP2C19 polymorphism on platelet reactivity (PR) and prognosis between CKD and non-CKD patients after stent implantation.
Methods: We enrolled 279 patients following stent implantation, taking dual antiplatelet therapy 100mg/day aspirin and 75mg/day clopidogrel, in this prospective study with 18 months follow-up. Patients were divided into CKD (n=112, male 67%) and non-CKD (n=167, male 71%) groups. CKD was defined as estimated glomerular filtration rate (eGFR) ≤60 mL/min/1.73m*m. Platelet reactivity using light transmission aggregometer was measured as response to clopidogrel. CYP2C19 polymorphism was also examined, and classified into three phenotypes: (1) extensive metabolizer (EM) carrying normal function alleles (CYP2C19*1/*1), (2) intermediate metabolizer (IM) carrying one loss-of-function (LOF) allele (*1/*2, *1/*3), and (3) poor metabolizer (PM) carrying two LOF alleles (*2/*2, *2/*3, *3/*3). Clinical endpoint was cardiovascular death, myocardial infarction, stroke, any urgent revascularization, and intraprocedural thrombotic events.
Results: Patients with CKD showed higher age compared with non-CKD (71.7 vs 67.6ys, P≤0.05). There was no difference in distribution of EM and IM between non-CKD and CKD (EM; 28% vs 41, IM; 47 vs 44), however, the ratio of PM was significantly higher in non-CKD than CKD (24.5 vs 14.2%, P=0.03). There were no differences in PR (4068 vs 4183AU*min, NS) and clinical outcomes (9.6 vs 11.6%, NS) between non-CKD and CKD. In non-CKD, the incidence of adverse clinical events was significantly higher in PM than EM (17.0 vs 4.2%, P=0.04), however, there were no differences among EM, IM, and PM in CKD. Intraprocedural thrombotic events were frequently found in PM of non-CKD patients compared with other genotypes of CKD or non-CKD.
Conclusions: In patients treated with stent implantation, the impact of CYP2C19 LOF polymorphism on clinical outcomes is more powerful in non-CKD compared with CKD patients.
- © 2013 by American Heart Association, Inc.