Burke Kerry A, McDermott John H, Wright Stuart J, Newman William G, Greaves Nicholas S
Manchester Centre for Genomic Medicine, St Mary's Hospital, Manchester University NHS Foundation Trust, Manchester, United Kingdom.
Division of Evolution, Infection, and Genomics, School of Biological Sciences, University of Manchester, Manchester, United Kingdom.
JVS Vasc Insights. 2024;2:100112. doi: 10.1016/j.jvsvi.2024.100112.
Lower extremity arterial disease (LEAD) is a prevalent condition that produces a significant burden on health care systems. Patients with LEAD have an increased risk of major adverse cardiovascular events as well as major adverse limb events. Despite significant variation in guidance on antiplatelet therapy for LEAD worldwide, many governing bodies recommend clopidogrel as the preferred single anti-platelet agent. Clopidogrel is also used frequently in post-revascularization regimens, either as a single agent or as part of dual antiplatelet therapy. Clopidogrel is a thienopyridine prodrug that is metabolized in the liver by the CYP2C19 enzyme. Genetic variations in are common and can influence an individual's ability to metabolize clopidogrel to its active metabolite.
This work completes a narrative review of the literature to consider whether genetic testing should be routinely implemented in patients who are to be prescribed clopidogrel to improve outcomes in patients with LEAD.
Recent advances in both cardiac and stroke medicine have demonstrated a role for patient genotyping to identify poor clopidogrel metabolizers and adopt alternative therapeutic strategies in these patient groups. This approach has been shown to improve clinical outcomes and has been incorporated into national and international guidance. Research studies suggest an association between loss of function alleles and adverse outcomes in patients with LEAD taking clopidogrel.
The introduction of a precision medicine strategy in vascular surgery may have the potential to significantly improve clinical outcomes in this complex group of patients with multiple comorbidities.
下肢动脉疾病（LEAD）是一种常见疾病，给医疗保健系统带来了沉重负担。LEAD患者发生主要不良心血管事件以及主要不良肢体事件的风险增加。尽管全球范围内关于LEAD抗血小板治疗的指南存在显著差异，但许多管理机构推荐氯吡格雷作为首选的单一抗血小板药物。氯吡格雷也经常用于血管重建术后的治疗方案中，既可以作为单一药物，也可以作为双重抗血小板治疗的一部分。氯吡格雷是一种噻吩并吡啶前体药物，在肝脏中由CYP2C19酶代谢。CYP2C19基因变异很常见，会影响个体将氯吡格雷代谢为其活性代谢物的能力。
本研究完成了一项文献综述，以探讨对于即将接受氯吡格雷治疗的LEAD患者，是否应常规进行基因检测以改善其治疗效果。
心脏病学和中风医学领域的最新进展表明，患者基因分型对于识别氯吡格雷代谢不良者并在这些患者群体中采用替代治疗策略具有重要作用。这种方法已被证明可以改善临床结果，并已纳入国家和国际指南。研究表明，功能丧失等位基因与服用氯吡格雷的LEAD患者的不良结局之间存在关联。
在血管外科手术中引入精准医学策略可能有潜力显著改善这类患有多种合并症的复杂患者群体的临床结局。
