Guirgis Mina, Thompson Peter, Jansen Shirley
Department of Vascular and Endovascular Surgery, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia.
Harry Perkins Medical Research Institute, Perth, Western Australia, Australia; Department of Medicine and Population Health, University of Western Australia, Perth, Western Australia, Australia.
J Vasc Surg. 2017 Nov;66(5):1576-1586. doi: 10.1016/j.jvs.2017.07.065.
Aspirin resistance (AR) and clopidogrel resistance (CR) are terms used to describe a reduction in the medication's efficacy in inhibiting platelet aggregation despite regular dosing. This review gives context to the clinical role and implications of antiplatelet resistance in peripheral arterial disease (PAD).
A review of English-language literature on AR and CR in PAD involving human subjects using PubMed and MEDLINE databases was performed in April 2017. A total of 2075 patients in 22 relevant studies were identified. To give this issue context, a review of the larger, more established literature on antiplatelet resistance in coronary disease was undertaken, identifying significant research associating resistance to major adverse cardiovascular events (MACEs).
Studies in the coronary arterial disease literature have strongly associated antiplatelet resistance with increased MACE. Prevalence of AR or CR in coronary disease appears to be >55% for each in some studies. Meta-analyses of >50 studies revealed that AR and CR are significantly associated with MACE (relative risk of 2.09 and 2.8, respectively). This adds further weight to the literature reporting antiplatelet resistance as an independent predictor of and a threefold risk factor for major adverse cardiovascular events. The prevalence of resistance in PAD in this review was comparable to that in the coronary disease literature, with AR and CR prevalence up to 60% and 65%, respectively. There is evidence that the adverse effects of antiplatelet resistance are significant in PAD. In fact, research directly studying stent thrombosis populations with either coronary arterial disease or PAD revealed more significantly impaired platelet responsiveness to clopidogrel and aspirin in PAD compared with similar individuals with coronary disease. AR in PAD was found in studies to be a significant risk factor for iliofemoral stent reocclusion (P = .0093) and stroke in patients with symptomatic carotid disease (P = .018). CR was found to be a significant, independent risk factor in predicting ischemic outcomes in several recent PAD studies (P < .0001). Loss-of-function carriers of enzyme CYP2C19, important in clopidogrel metabolism, have a 30% greater risk of ischemic events (P < .001). Importantly, less antiplatelet drug resistance may be encountered with newer antiplatelet agents, including ticagrelor and prasugrel, because of reduced enzymatic polymorphisms.
The limited research addressing AR and CR in PAD suggests that further research is required to clarify the role of platelet assays and potential for individualized antiplatelet therapy.
阿司匹林抵抗（AR）和氯吡格雷抵抗（CR）是用于描述尽管规律给药但药物抑制血小板聚集功效降低的术语。本综述阐述了抗血小板抵抗在周围动脉疾病（PAD）中的临床作用及影响。
2017年4月，利用PubMed和MEDLINE数据库对有关PAD中AR和CR且涉及人类受试者的英文文献进行了综述。在22项相关研究中总共确定了2075例患者。为了更好地理解这个问题，还对关于冠心病中抗血小板抵抗的更广泛、更成熟的文献进行了综述，确定了将抵抗与主要不良心血管事件（MACE）相关联的重要研究。
冠心病文献中的研究已将抗血小板抵抗与MACE增加紧密关联。在一些研究中，冠心病中AR或CR的患病率似乎每项都>55%。对50多项研究的荟萃分析显示，AR和CR与MACE显著相关（相对风险分别为2.09和2.8）。这进一步支持了将抗血小板抵抗作为主要不良心血管事件的独立预测因素和三倍风险因素的文献报道。本综述中PAD的抵抗患病率与冠心病文献中的相当，AR和CR患病率分别高达60%和65%。有证据表明抗血小板抵抗在PAD中的不良影响显著。事实上，直接研究冠心病或PAD支架血栓形成人群的研究表明，与类似的冠心病患者相比，PAD患者对氯吡格雷和阿司匹林的血小板反应性受损更明显。在研究中发现，PAD中的AR是髂股支架再闭塞（P = 0.0093）和有症状颈动脉疾病患者中风（P = 0.018）的重要危险因素。在最近的几项PAD研究中，CR被发现是预测缺血性结局的重要独立危险因素（P < 0.0001）。在氯吡格雷代谢中起重要作用的酶CYP2C19功能缺失携带者发生缺血性事件的风险高30%（P < 0.001）。重要的是，由于酶多态性减少，包括替格瑞洛和普拉格雷在内的新型抗血小板药物可能遇到的抗血小板药物抵抗较少。
针对PAD中AR和CR的研究有限，这表明需要进一步研究以阐明血小板检测的作用及个体化抗血小板治疗的潜力。
