Abstract 13046: Platelet Reactivity During Antiplatelet Therapy in Patients with CYP3A5 Polymorphism Depends on Chronic Kidney Disease (CKD)
Background: Several studies report that the platelet reactivity (PR) varies widely according to CYP3A5 polymorphism during dual antiplatelet therapy. Antiplatelet efficacy of clopidogrel is reduced in patients with chronic kidney disease (CKD). The aim of this study was to examine whether PR is associated with CKD according to CYP3A5 genotypes.
Methods: We examined the PR by light transmittance aggregometer in patients who underwent coronary stent implantation (n=103, 69ys, male; 70%) with dual antiplatelet therapy including 100mg/day aspirin and 75mg/day clopidogrel. The residual PR was measured two times at the time of stent implantation and the chronic phase (9 months after stent implantation), respectively. CYP3A5 polymorphism was examined, and classified into two phenotypes: (1) patients with CYP3A5 expressor genotype (at least one normal function allele, *1/*1, *1/*3), (2) patients with CYP3A5 non-expressor genotype (two loss-of-function (LOF) alleles, *3/*3). CKD was defined as estimated glomerular filtration rate (eGFR) ≤60ml/min/1.73m*m.
Results: The ratio of CYP3A5 expressor and non-expressor genotypes was 40 versus 60%. In patients with CYP3A5 expressor genotype, PR was significantly decreased in the late phase compared with the early phase regardless of CKD (early vs. late: non-CKD, 4792 vs. 3379, n=25, P=0.0007; CKD, 5117 vs. 3604, n=9, P=0.007). In patients with CYP3A5 non-expressor genotype, in cases of non-CKD, PR in the early phase was significantly decreased in the late phase (early vs. late; 4416 vs. 3522, n=39, p=0.014), however, in cases of CKD patients with CYP3A5 non-expressor genotype, there was no significant difference in PR between in the early and late phase (early vs. late; 4545 vs. 3647, n=28, NS). In short, antiplatelet efficacy of clopidogrel was not sufficient in CKD patients with CYP3A5 non-expressor genotype even in the late phase.
Conclusions: These results indicate that the PR during dual antiplatelet therapy may depend on renal function in patients with CYP3A5 non-expressor genotype. Thus, there is a possibility that the impact of CKD on PR during antiplatelet therapy is more powerful in patients with CYP3A5 non-expressor genotype compared with CYP3A5 expressor genotype.
- © 2013 by American Heart Association, Inc.