Kim Ho-Sook, Chang Kiyuk, Koh Yoon-Seok, Park Mahn-Won, Choi Yun-Seok, Park Chul-Soo, Oh Minkyung, Kim Eun-Young, Shon Ji-Hong, Shin Jae-Gook, Seung Ki-Bae
Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine, Busan, Republic of Korea.
Circ Cardiovasc Genet. 2013 Oct;6(5):514-21. doi: 10.1161/CIRCGENETICS.113.000109. Epub 2013 Sep 9.
More intensive platelet suppression is required in patients with acute myocardial infarction (AMI) than in those with stable angina because of differential platelet activation between AMI and stable angina. In this context, CYP2C19 genotype leading to reduced active metabolite formation may profoundly affect the clinical outcome of clopidogrel therapy in patients with AMI compared with those with stable angina.
Effects of CYP2C19 genotypes on the clinical outcome of clopidogrel therapy were evaluated in 2188 patients (532 patients with AMI and 1656 patients with stable angina) undergoing percutaneous coronary intervention. The primary clinical outcome was a composite of major adverse cardiac and cerebrovascular events defined as death from any cause, nonfatal myocardial infarction, or stroke during 1 year of clopidogrel therapy. Compared with extensive metabolizer, the CYP2C19 poor metabolizer was significantly associated with higher risk of major adverse cardiac and cerebrovascular events in patients with AMI (hazard ratio, 2.88; 95% confidence interval, 1.27-6.53; P=0.011). However, this finding was not seen in patients with stable angina. A significant interaction between CYP2C19 genotypes and disease subsets of AMI and stable angina was identified with respect to major adverse cardiac and cerebrovascular events (adjusted interaction P=0.045). The patients with AMI showed lower percent inhibition of P2Y12 compared with patients with stable angina in CYP2C19 poor metabolizer or CYP2C19 intermediate metabolizer genotype groups but not in CYP2C19 extensive metabolizer genotype group.
CYP2C19 poor metabolizer is associated with poor clinical outcome of clopidogrel therapy in Asian patients with AMI but not in those with stable angina possibly because of differential requirement of platelet suppression in patients with AMI and stable angina.
URL: clinicaltrials.gov. Identifier: NCTO1239914.
由于急性心肌梗死（AMI）和稳定型心绞痛患者血小板激活情况不同，AMI患者比稳定型心绞痛患者需要更强化的血小板抑制。在此背景下，导致活性代谢产物生成减少的CYP2C19基因型可能比稳定型心绞痛患者更深刻地影响AMI患者氯吡格雷治疗的临床结局。
在2188例接受经皮冠状动脉介入治疗的患者（532例AMI患者和1656例稳定型心绞痛患者）中评估CYP2C19基因型对氯吡格雷治疗临床结局的影响。主要临床结局是主要不良心脑血管事件的复合终点，定义为氯吡格雷治疗1年内任何原因导致的死亡、非致死性心肌梗死或卒中。与快代谢型相比，CYP2C19慢代谢型与AMI患者发生主要不良心脑血管事件的风险显著升高相关（风险比，2.88；95%置信区间，1.27 - 6.53；P = 0.011）。然而，在稳定型心绞痛患者中未观察到这一发现。就主要不良心脑血管事件而言，CYP2C19基因型与AMI和稳定型心绞痛疾病亚组之间存在显著交互作用（校正交互作用P = 0.045）。在CYP2C19慢代谢型或CYP2C19中间代谢型基因型组中，AMI患者的P2Y12抑制百分比低于稳定型心绞痛患者，但在CYP2C19快代谢型基因型组中并非如此。
CYP2C19慢代谢型与亚洲AMI患者氯吡格雷治疗的不良临床结局相关，但与稳定型心绞痛患者无关，这可能是因为AMI和稳定型心绞痛患者对血小板抑制的需求不同。
网址：clinicaltrials.gov。标识符：NCTO1239914。
