Tailored Adjunctive Cilostazol Therapy Based on CYP2C19 Genotyping in Patients With Acute Myocardial Infarction - The CALDERA-GENE Study.

Abstract

Patients with reduced-function CYP2C19 genotypes on dual antiplatelet therapy (DAPT) with aspirin and clopidogrel show higher clinical risk for acute myocardial infarction (AMI). We investigated the effect of CYP2C19 genotype-tailored adjunctive cilostazol therapy on treatment of AMI.Methods and Results:The study group of 138 patients with suspected AMI were screened for CYP2C19 genotype immediately after percutaneous coronary intervention (PCI) using a SPARTAN RX point-of-care device. Carriers of the CYP2C19 reduced-function allele were randomized into DAPT (Carrier/DAPT) and DAPT plus 14-day cilostazol (Carrier/DAPT+Cilostazol) groups, while noncarriers were treated with DAPT (Noncarrier/DAPT). After exclusion of 10 patients, the remaining 128 patients were analyzed for P2Y12 reaction unit (PRU) using VerifyNow®P2Y12 system, and levels of biomarkers immediately after, and 1, 14, and 28 days after PCI. DAPT+Cilostazol reduced PRU levels in carriers (n=46) to those found in the Noncarrier/DAPT group (n=40), and significantly lower than those of the Carrier/DAPT group (n=42) at 14 days post-PCI. Discontinuation of cilostazol for 14 days was associated with a significant rise in PRU levels to those of the Carrier/DAPT group at 28 days post-PCI. Plasma B-type natriuretic peptide levels at 14 days post-PCI were lower in Carrier/DAPT+Cilostazol than in the other 2 groups, and the levels increased to those of the other groups at 28 days post-PCI after withdrawal of cilostazol. Adjunctive cilostazol therapy tailored to CYP2C19 genotype seemed useful in AMI patients with the CYP2C19 reduced-function allele.