Kerry A. Burke MBBS, MA, FRCS , John H. McDermott MCRP, MBChB, BSc, MSc , Stuart J. Wright MSc, PhD , William G. Newman MBChB, MA, FRCP, PhD , Nicholas S. Greaves MBChB, PhD, FRCS
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引用次数: 0
Abstract
Objective
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 CYP2C19 are common and can influence an individual’s ability to metabolize clopidogrel to its active metabolite.
Methods
This work completes a narrative review of the literature to consider whether CYP2C19 genetic testing should be routinely implemented in patients who are to be prescribed clopidogrel to improve outcomes in patients with LEAD.
Results
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 CYP2C19 loss of function alleles and adverse outcomes in patients with LEAD taking clopidogrel.
Conclusions
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.
目标下肢动脉疾病(LEAD)是一种普遍存在的疾病,给医疗保健系统造成了沉重负担。LEAD 患者发生主要不良心血管事件和主要不良肢体事件的风险增加。尽管全球范围内针对 LEAD 的抗血小板治疗指南存在很大差异,但许多管理机构都建议将氯吡格雷作为首选的单一抗血小板药物。氯吡格雷也经常作为单药或双重抗血小板疗法的一部分用于血管重建后的治疗方案。氯吡格雷是一种噻吩吡啶原药,在肝脏中通过 CYP2C19 酶进行代谢。CYP2C19的基因变异很常见,可影响个体将氯吡格雷代谢为其活性代谢物的能力。结果近期心脏和中风医学的进步表明,患者基因分型可用于识别氯吡格雷代谢不良者,并在这些患者群体中采取替代治疗策略。这种方法已被证明可以改善临床疗效,并已被纳入国家和国际指南。研究表明,在服用氯吡格雷的 LEAD 患者中,CYP2C19 功能缺失等位基因与不良预后之间存在关联。结论在血管外科中引入精准医疗策略可能会显著改善这一具有多种并发症的复杂患者群体的临床预后。