Abstract 14257: Improvement of Clopidogrel Hypo-Responsiveness by Cilostazol Addition to the Dual Antiplatelet Therapy in PCI Patients Carrying CYP2C19 Gene Polymorphism
Background: Patients assessed as the clopidogrel hypo-responder using ex vivo platelet function assays have an increased risk of stent thrombosis. Recent studies show that CYP2C19 gene polymorphisms are associated with clopidogrel hypo-responder. The purpose of this study was to verify the efficacy of addition of a specific PDE-3 inhibitor cilostazol to the standard dual antiplatelet therapy (triple antiplatelet therapy; TAPT) on clopidogrel hypo-responder in PCI patients carrying CYP2C19 *2 and/or *3 alleles.
Methods: We analyzed three platelet function tests and CYP2C19 genotypes (enhanced metabolizer: EM, intermediate metabolizer: IM, poor metabolizer: PM) in 158 PCI patients treated by clopidogrel+aspirin (DAPT), and in 29 PCI patients treated by TAPT. Platelet function was measured by optical aggregometry with 20μM ADP(LTA-ADP), VerifyNow-P2Y12 assay and vasodilator-stimulated phosphoprotein phosphorylation (VASP) index.
Results: In the TAPT group, number of risk factors (RF) were significantly more than that in the DAPT group (No of RF > 3; 65.5% vs 37.3%, p=0.005). There were 62 patients (41.1%) classified as EM, 70(44.3%) as IM and 21(14.6%) as PM in DAPT groups, whereas there were 11 patients (37.9%) as EM, 13(44.8%) as IM, and 5(17.2%) as PM in TAPT group. The rates of inhibition of VASP index by DAPT were 38.0±18.9% in EM, 51.5±15.0% in IM, and 63.5±12.9% in PM, whereas those by TAPT were 21.8±13.2% in EM, 33.4±17.8% in IM and 36.4±10.3% in PM. Similar results were obtained in LTA-ADP and VerifyNow-P2Y12 assay.
Conclusions: Antiplatelet effect of clopidogrel was strongly affected by CYP2C19 gene polymorphism, and administration of cilostazol in addition to the standard dual therapy led to an enhanced inhibition of platelet aggregation in PCI patients even if carrying the loss of function function CYP2C19 *2 and *3 alleles. Adjunctive use of cilostazol to the dual therapy may be useful alternative for patients with clopidogrel hypo-responder.
- © 2010 by American Heart Association, Inc.