背景:外周动脉疾病(PAD)影响全球约2.36亿人。因此,本研究旨在探讨CYP2C19基因型多态性与PAD患者血运重建后氯吡格雷抵抗(CR)的关系。
方法:总共,对345例接受PAD血运重建的患者进行了5年的监测,并确定了缺血事件的危险因素。测量血小板反应性和CYP2C19基因型,患者被归类为正常,中间,或基于基因型的代谢不良者。研究终点定义为缺血事件,包括主要不良心血管或肢体事件,或全因死亡。
结果:在这项研究中,PAD血运重建后的缺血事件与患者年龄相关,之前的轻微截肢,血运重建前的卢瑟福类别,血运重建的适应症,血管重建术前踝关节指数,CYP2C19表型,和CR。中间和不良的新陈代谢,血运重建前的卢瑟福类别,CR和CR是PAD血运重建后发生缺血事件的独立危险因素。同样,中间和不良的新陈代谢,血运重建前的卢瑟福类别,CR和CR是PAD患者血运重建后5年内发生缺血事件的独立危险因素。中代谢者和代谢不良者比正常代谢者具有更高的血小板反应性和CR风险。然而,代谢不良者的血小板反应性和CR风险高于中间代谢不良者.此外,缺血事件的危险比随血小板反应性的增加而增加.与正常代谢者相比,这种作用在中度和不良代谢者中更为普遍。
结论:PAD血运重建后缺血事件受独立危险因素影响。氯吡格雷代谢降低可增加PAD血运重建后患者的血小板反应性和CR。此外,在代谢中度和代谢不良患者中,高血小板反应性与缺血事件风险增加相关.
BACKGROUND: Peripheral arterial disease (PAD) affects approximately 236 million people worldwide. Therefore, this study aimed to investigate the relationship between CYP2C19 genotype polymorphisms and clopidogrel resistance (CR) following revascularization in patients with PAD.
METHODS: In total, 345 patients who underwent PAD revascularization were monitored for five years and risk factors for ischemic events were identified. Platelet reactivity and CYP2C19 genotypes were measured, and patients were classified as normal, intermediate, or poor metabolizers based on their genotypes. The study endpoint was defined as an ischemic event, that encompassed major adverse cardiovascular or limb events, or all-cause death.
RESULTS: In this study, ischemic events following PAD revascularization were associated with patient age, prior minor amputation, the Rutherford category before revascularization, indications for revascularization, index ankle-branchial index before revascularization, CYP2C19 phenotypes, and CR. Intermediate and poor metabolism, the Rutherford category before revascularization, and CR were independent risk factors for ischemic events in patients after PAD revascularization. Similarly, intermediate and poor metabolism, the Rutherford category before revascularization, and CR were independent risk factors for ischemic events in patients with PAD after revascularization within five years. Intermediate and poor metabolizers had a higher platelet reactivity and risk of CR than normal metabolizers. However, poor metabolizers had a higher platelet reactivity and risk of CR than intermediate metabolizers. Furthermore, the hazard ratio for ischemic events increased with platelet reactivity. This effect was more prevalent in intermediate and poor metabolizers than in normal metabolizers.
CONCLUSIONS: Ischemic events in patients after PAD revascularization were affected by independent risk factors. Decreased clopidogrel metabolism increased the platelet reactivity and CR in patients after PAD revascularization. Furthermore, high platelet reactivity was associated with an increased risk of ischemic events in patients with intermediate and poor metabolism.