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目的:探讨经皮冠状动脉介入术(PCI)后接受氯吡格雷治疗的患者中,细胞色素P450 2C19(CYP2C19)*2基因多态性(681A)与支架内血栓形成的相关性,以及服用钙通道阻滞剂(CCBs)与支架内血栓形成的相关性。方法:检测1 738例冠心病PCI术后患者的CYP2C19基因多态性,并将这些患者分为CCBs组和非CCBs组,采用比浊法检测二磷酸腺苷(ADP)途径诱导的血小板最大聚集率(MPAR),比较两组患者MPAR及支架内血栓形成率的差异。结果:19例(2.4%)CYP2C19*2基因型的患者(包括CYP2C19*2/*2或*1/*2)和7例(0.75%)基因型为CYP2C19*1/*1的患者发生了明确的支架内血栓形成;CYP2C19*2基因型患者支架内血栓形成的发生率明显高于CYP2C19野生型纯合子患者(CYP2C19*1/*1)(风险比为4.26,95%可信区间为1.28～9.22,P<0.05);基因型为CYP2C19*1/*1的患者发生支架内血栓形成的风险最低,而基因型为CYP2C19*2/*2的患者支架内血栓形成的风险最高(风险比为0.568,95%可信区间为0.308～2.070,P<0.01);CCBs组和非CCBs组MPAR及支架内血栓形成率差异无统计学意义。结论:PCI术后接受氯吡格雷治疗的冠心病患者中,CYP2C19*2基因型患者支架内血栓形成的风险增加,而服用CCBs不会导致氯吡格雷抗血小板聚集作用减弱以及支架内血栓形成事件增加。
Objective: To investigate the relationship between CYP2C19 * 2 polymorphism (681A) and stent thrombosis in patients receiving clopidogrel after percutaneous coronary intervention (PCI) Correlation between channel blockers (CCBs) and stent thrombosis. Methods: CYP2C19 gene polymorphism was detected in 1 388 patients with coronary artery disease (PCI) after PCI. The patients were divided into CCBs group and non-CCBs group. The maximal platelet aggregation induced by adenosine diphosphate (ADP) Rate (MPAR), MPAR and stent thrombosis rate differences between the two groups were compared. RESULTS: Nineteen (2.4%) CYP2C19 * 2 genotype patients (including CYP2C19 * 2 / * 2 or * 1 / * 2) and 7 patients (0.75%) had CYP2C19 * 1 / * 1 genotype The incidence of stent thrombosis was significantly higher in patients with CYP2C19 * 2 than CYP2C19 wild-type homozygotes (CYP2C19 * 1 / * 1) (hazard ratio was 4.26, 95% confidence interval was 1.28 ~ 9.22, P <0.05). Patients with genotype CYP2C19 * 1 / * 1 had the lowest risk of stent thrombosis and patients with genotype CYP2C19 * 2 / * 2 had the highest risk of stent thrombosis (hazard ratio 0.568, 95% confidence interval was 0.308 ~ 2.070, P <0.01). There was no significant difference in MPAR and stent thrombosis between CCBs group and non-CCBs group. CONCLUSIONS: CYP2C19 * 2 genotype patients have an increased risk of stent thrombosis in patients with coronary artery disease treated with clopidogrel after PCI, whereas taking CCBs does not result in an impaired antiplatelet aggregation of clopidogrel and stent thrombosis events increase.