Abstract 12387: Association of CYP2C19 Polymorphism and Peripheral Endothelial Dysfunction With Clinical Outcome is More Important in Non-Chronic Kidney Disease (CKD) Than CKD Patients Following Coronary Stent Implantation
Introduction: Chronic kidney disease (CKD) and CYP2C19 polymorphism are associated with increased risk of cardiovascular events following coronary stent implantation in patients with dual antiplatelet therapy. Endothelial dysfunction has recently been reported to correlate with adverse cardiovascular events in coronary heart disease. The aim of this study was to examine the differential impact of these factors on clinical outcome in patients with or without CKD.
Methods: We enrolled 556 consecutive patients after coronary stent implantation. All patients received aspirin (100mg/d) and clopidogrel (75mg/d for long-term treatment or a loading dose of 300mg). Patients were divided into two groups; CKD (n=230, male 70%), and non-CKD (n=326, male 72%) groups. CYP2C19 genotype and platelet reactivity by a light transmission aggregometry were examined, and high platelet reactivity was defined as above 5000 AU*min. Peripheral endothelial dysfunction was expressed as reactive hyperemia index (RHI) using reactive hyperemia peripheral arterial tonometry, and low RHI was defined as under the median value of RHI. Clinical events were evaluated according to non-CKD and CKD.
Results: There was no significance in the rate of CYP2C19 loss-of-function (LOF) allele carrier (64.6% versus 66.8%; P=0.65) and the rate of clinical outcome (12.9% versus 15.2%; P=0.456) between the non-CKD and CKD group, but the rate of high platelet reactivity was significantly more in the CKD group than in the non-CKD group (40.3% versus 29.2%; P=0.015). In the non-CKD group alone, the incidence of cardiovascular event was significantly higher in low RHI than high RHI patients (19.7% versus 7.7%; P=0.003). Multivariate analysis identified RHI (hazard ratio [HR]: 0.07; 95% confidence interval [CI]: 0.014 to 0.346; P=0.001) and CYP2C19 LOF carrier (HR: 2.669; 95% CI 1.207 to 5.903; P=0.015) as independent and significant predictors of cardiovascular events in the non-CKD group, but not in the CKD group.
Conclusions: Peripheral endothelial dysfunction and CYP2C19 polymorphism were independently associated with adverse cardiovascular events and were independent predictors of clinical outcome in non-CKD patients following coronary stent implantation.
- Percutaneous coronary intervention (PCI)
- Endothelial function
- Coronary artery disease
Author Disclosures: N. Tabata: None. S. Hokimoto: None. T. Akasaka: None. Y. Arima: None. K. Kaikita: None. K. Nakagawa: None. H. Ogawa: Other Research Support; Modest; AstraZeneca, Astellas, Boehringer lngelheim, Bristol-Myers Squibb, Daiichi Sankyo, Dainippon Sumitomo Pharma, Kowa, MSD, Novartis, Pfizer, Sanofi, Takeda. Other Research Support; Significant; Bayer, Chugai, Otsuka. Honoraria; Modest; AstraZeneca, Bayer, Pfizer, Sanofi, Takeda. Honoraria; Significant; Daiichi Sankyo, MSD.
- © 2014 by American Heart Association, Inc.