Abstract 11886: Chronic Kidney Disease Status Modifies the Association of CYP2C19 Polymorphism in Predicting Clinical Outcomes Following Coronary Stent Implantation
Introduction: There is some controversy regarding the effect of CYP2C19 polymorphism on clinical outcome in coronary heart disease patients with dual antiplatelet therapy (DAPT). Chronic kidney disease (CKD) is associated with increased risk of cardiovascular event.
Hypothesis: We hypothesized that CYP2C19 polymorphism correlates with adverse cardiovascular events without the factor of CKD. The aim of this study was to investigate whether CKD status modifies the association of CYP2C19 polymorphism in predicting outcomes in a prospective cohort study.
Methods: We enrolled 331 patients following elective percutaneous coronary intervention with DAPT. CKD was defined as estimated glomerular filtration rate <60 mL/min/1.73m*m, and patients were divided into two groups: CKD (n=154, male 69.5%) and non-CKD (n=177, male 73.6%) groups. Platelet reactivity by a light transmission aggregometry was examined, and high platelet reactivity was defined as above 5000 AU*min. CYP2C19 polymorphism were examined, and the subjects were divided into two groups according to the carriage of CYP2C19 loss-of-function alleles: Carriers (n=220) and non-Carriers (n=111). Clinical events were evaluated according to CKD and Carrier status.
Results: There was no significant difference in the proportion of carriers between CKD and non-CKD group, and no significant difference in clinical characteristics between Carriers and non-Carriers in both CKD and non-CKD groups. The proportion of high platelet reactivity was significantly higher in CKD than non-CKD (35.9% vs 23.9%; P=0.025), and Carriers than non-Carriers in both CKD (42.4% vs 21.7%; P=0.016) and non-CKD groups (34.3% vs 3.7%; P<0.001). In the non-CKD group alone, the incidence of cardiovascular event was significantly higher in Carriers than non-Carriers (13.7% versus 1.7%; P=0.013); however there was no difference in the CKD group. Multivariate analysis identified Carrier as an independent predictor of cardiovascular events in the non-CKD group (hazard ratio: 8.048; 95% confidence interval: 1.066 to 60.757; P=0.043), but not in the CKD group.
Conclusions: The association of CYP2C19 polymorphism with clinical outcome is more important in non-CKD than CKD patients following coronary stent implantation.
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.