细胞色素P450 2C19（CYP2C19）基因多态性及氯吡格雷反应性对冠心病患者PCI术后长期预后的影响
Effect of cytochrome P450 2C19 (CYP2C19) gene polymorphism and clopidogrel reactivity on long term prognosis of patients with coronary heart disease after PCI.
作者信息
Hu Cheng-Yan, Wang Yan-Ling, Fan Zhen-Xing, Sun Xi-Peng, Wang Shuai, Liu Zhi
机构信息
Department of Geriatrics, Fu Xing Hospital, Capital Medical University, Beijing, China.
Department of Cardiology, Xuanwu Hospital Capital Medical University, Beijing, China.
出版信息
J Geriatr Cardiol. 2024 Jan 28;21(1):90-103. doi: 10.26599/1671-5411.2024.01.004.
OBJECTIVE
To investigate the impact of CYP2C19 gene polymorphism on clopidogrel reactivity and its association with long-term clinical outcome in patients with coronary heart disease (CHD) undergoing percutaneous coronary intervention (PCI).
METHODS
In total, 675 patients were enrolled. Based on the platelet inhibition rate, patients were categorized into two groups: clopidogrel low responsiveness (CLR) and normal clopidogrel responsiveness (NCR). The CLR group was divided into ticagrelor and clopidogrel group based on the antiplatelet drugs used in the follow-up treatment. Patients were classified into three groups (normal metabolizer, intermediate metabolizer, and poor metabolizer) based on the CYP2C19 genotype. We aimed to evaluate the impact of CYP2C19 gene polymorphism on clopidogrel reactivity. The cumulative rates of 12-month all-cause deaths, major adverse cardiovascular events (MACCEs), and bleeding events were calculated.
RESULTS
CLR was observed in 44.4% of the overall population. Significant differences were observed in the platelet inhibition rate of clopidogrel among the three metabolic genotypes ( < 0.05). At the 12-month follow-up, 13 patients (1.9%) died and 96 patients (14.2%) experienced MACCEs. Patients with CLR (9.6% . 11.7% . 22.1%, < 0.05) or poor metabolizer (10.7% . 16.4% . 22.6%, = 0.026) experienced a higher rate of MACCEs. A MACCEs risk score between zero and two was calculated. The highest incidence of MACCEs significantly increased with the 2-positive results, and the area under the curve (AUC) was 0.712 (95% CI: 0.650-0.774, < 0.05). There was no significant difference between the group with a score of one and the occurrence of MACCEs ( > 0.05).
CONCLUSIONS
Low response to clopidogrel in CHD patients is correlated with CYP2C19 gene polymorphism. CYP2C19 genotyping combined with platelet reactivity is an independent predictor of 12-months MACCEs in patients with clopidogrel treatment after PCI, which is better than either test alone.
目的
探讨CYP2C19基因多态性对冠心病（CHD）行经皮冠状动脉介入治疗（PCI）患者氯吡格雷反应性的影响及其与长期临床结局的关系。
方法
共纳入675例患者。根据血小板抑制率，将患者分为两组：氯吡格雷低反应性（CLR）组和氯吡格雷正常反应性（NCR）组。CLR组根据后续治疗中使用的抗血小板药物分为替格瑞洛组和氯吡格雷组。根据CYP2C19基因型将患者分为三组（正常代谢者、中间代谢者和慢代谢者）。我们旨在评估CYP2C19基因多态性对氯吡格雷反应性的影响。计算12个月全因死亡、主要不良心血管事件（MACCE）和出血事件的累积发生率。
结果
总体人群中44.4%观察到CLR。三种代谢基因型的氯吡格雷血小板抑制率存在显著差异（<0.05）。在12个月的随访中，13例患者（1.9%）死亡，96例患者（14.2%）发生MACCE。CLR患者（9.6%、11.7%、22.1%，<0.05）或慢代谢者（10.7%、16.4%、22.6%，=0.026）发生MACCEs的发生率较高。计算了MACCEs风险评分为0至2分。MACCEs的最高发生率随2项阳性结果显著增加，曲线下面积（AUC）为0.712（95%CI：0.650-0.774，<0.05）。评分为1分的组与MACCEs的发生之间无显著差异（>0.05）。
结论
CHD患者对氯吡格雷的低反应与CYP2C19基因多态性相关。CYP2C19基因分型联合血小板反应性是PCI术后接受氯吡格雷治疗患者12个月MACCEs的独立预测指标，优于单独任何一项检测。
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