Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University.
Department of Cardiovascular Medicine, Japanese Red Cross Kumamoto Hospital.
Circ J. 2018 May 25;82(6):1517-1525. doi: 10.1253/circj.CJ-18-0197. Epub 2018 May 8.
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.
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 VerifyNowP2Y12 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.
接受阿司匹林和氯吡格雷双联抗血小板治疗（DAPT）的 CYP2C19 功能降低基因型的患者发生急性心肌梗死（AMI）的临床风险较高。我们研究了 CYP2C19 基因型指导的辅助西洛他唑治疗对 AMI 的治疗效果。
在经皮冠状动脉介入治疗（PCI）后，立即使用 SPARTAN RX 即时护理设备对 138 例疑似 AMI 的患者进行 CYP2C19 基因型筛查。携带 CYP2C19 功能降低等位基因的患者被随机分为 DAPT（携带/DAPT）和 DAPT 加 14 天西洛他唑（携带/DAPT+Cilostazol）组，而非携带者接受 DAPT（非携带者/DAPT）治疗。排除 10 例患者后，其余 128 例患者使用 VerifyNow P2Y12 反应单位（PRU）系统进行分析，并在 PCI 后即刻以及 1、14 和 28 天检测生物标志物水平。DAPT+Cilostazol 将携带者（n=46）的 PRU 水平降低至非携带者/DAPT 组（n=40）的水平，且在 PCI 后 14 天显著低于携带者/DAPT 组（n=42）。西洛他唑停药 14 天与 PCI 后 28 天时 PRU 水平恢复至携带者/DAPT 组水平相关。PCI 后 14 天的血浆 B 型利钠肽水平在携带者/DAPT+Cilostazol 组中低于其他 2 组，在停用西洛他唑后 28 天恢复至其他组水平。
针对 CYP2C19 基因型的辅助西洛他唑治疗似乎对携带 CYP2C19 功能降低等位基因的 AMI 患者有效。
