冠心病阿司匹林抵抗的研究与对策

阿司匹林是冠心病患者长期抗血小板治疗的基石, 同其他抗血小板药物一样, 阿司匹林也存在抗血小板药物 抵抗现象, 若发生阿司匹林抵抗, 可能会增加冠心病患者心血管事件风险。目前已有多项研究对抗血小板药物抵抗 进行了探究, 文章针对阿司匹林抵抗的定义、相关机制、实验室检测、临床影响及可能有效的治疗干预措施等研究进 展进行概述, 旨在提高临床医生对阿司匹林抵抗的认识, 并科学优化冠心病患者的抗血小板治疗。     

阿司匹林抵抗产生机制的研究进展

抗血小板药物阿司匹林广泛运用于心血管疾病的一级和二级预防中。临床上服用阿司匹林治疗的患者对该药物的反应性差异很大,有的患者的反应性很差甚至无反应,称之为阿司匹林抵抗。导致阿司匹林抵抗的机制,包括依从性差、药物间的相互作用和剂量不足等。通过进一步研究阿司匹林抵抗的机制,有助于优化抗血小板治疗。     

缺血性卒中与血小板抵抗现象

目前,阿司匹林联合氯吡格雷是临床抗血小板聚集的一线药物.然而,由于抗血小板聚集药物抵抗现象[1],并非所有卒中患者对抗血小板治疗有效,抗血小板治疗后仍然有部分患者再次出现缺血性卒中.现就阿司匹林和氯吡格雷抵抗的可能机制及其与基因多态性的关系综述如下. 1 阿司匹林抵抗 阿司匹林抵抗通常是指阿司匹林治疗未能引起预期的生物学效应[如抑制血小板聚集、抑制血栓素A2（TXA2）的生物合成、使出血时间延长]或未能预防动脉硬化血栓事件的现象,可分为临床阿司匹林抵抗和生化阿司匹林抵抗.因为阿司匹林的作用靶点是血小板的脂肪酸环氧化酶（COX-1）,因此实验室常通过检测TXA2的生成和依赖于血栓素的血小板功能来评估阿司匹林对血小板的抑制效应,从而鉴定生化阿司匹林抵抗患者.由于引发血管事件因素较多,抗血小板治疗不可能切断所有危险因素,故临床阿司匹林抵抗倍受争议.相关研究表明,在规律服用阿司匹林的患者中,真正的阿司匹林抵抗发生率不足5％.同时认为,生化阿司匹林抵抗为血管事件独立的危险因素.     

阿司匹林抵抗的研究进展

阿司匹林作为抗血小板药物,能够有效地预防血栓栓塞事件的发生。但临床以及实验室研究证实,存在阿司匹林抗血小板作用减弱或者无效的特定人群,被称为阿司匹林抵抗。而这种现象确切的发生机制尚未明确,目前的研究证实,阿司匹林抵抗的发生与临床合并症、药理学特性以及患者基因多态性等因素密切相关,但对其诊断和治疗尚缺乏有效手段。因而研究阿司匹林抵抗发生的机制,为治疗提供新靶点。     

阿司匹林抵抗的研究进展

阿司匹林作为抗血小板药物，能够有效地预防血栓栓塞事件的发生。但临床以及实验室研究证实，存在阿司匹林抗血小板作用减弱或者无效的特定人群，被称为阿司匹林抵抗。而这种现象确切的发生机制尚未明确，目前的研究证实，阿司匹林抵抗的发生与临床合并症、药理学特性以及患者基因多态性等因素密切相关，但对其诊断和治疗尚缺乏有效手段。因而研究阿司匹林抵抗发生的机制，为治疗提供新靶点。     

临床阿司匹林抵抗机制研究

阿司匹林在心肌梗死、缺血性脑血管病的预防中是一种有效的抗血小板药物.但在长期随访中发现,应用阿司匹林治疗的冠心病患者仍有可能发生血栓栓塞事件,这称为临床阿司匹林抵抗.现分析了人体内血栓形成时血小板所处的环境,阿司匹林的作用机制及环氧化酶(COX)的生物学功能,并着重分析了临床阿司匹林抵抗的可能机制.     

阿司匹林抵抗的发生机理及临床意义

小剂量阿司匹林的抗血小板聚集作用在心脑血管疾病的预防治疗当中得到广泛应用 ,但阿司匹林抵抗的出现限制了其临床疗效 ,本文就血小板聚集检测方法、阿司匹林抵抗发生机制、流行病学特征及其对临床的指导意义分别加以阐述。     

阿司匹林抵抗与脑卒中防治的现状

阿司匹林目前是预防缺血性脑卒中复发的最有效的抗血小板聚集药物,但很多患者长期规律口服治疗剂量的阿司匹林仍不能有效地阻止血栓性疾病的复发,即存在"阿司匹林抵抗现象"。其发生机制可能与药物的剂量、患者依从性、药物的相互作用、疾病的影响及基因多态性等有关。临床医师应明确阿司匹林抵抗的产生机制,并在临床上采取合适的措施来减少阿司匹林抵抗,从而取得理想的缺血性卒中预防及治疗效果。     

阿司匹林抵抗

研究表明在接受阿司匹林治疗的心血管疾病患者中有5%～45%存在阿司匹林抵抗,由于全球有大量的患者依赖阿司匹林的抗血小板治疗,所以关于阿司匹林抵抗的研究已经引起广泛关注.本文综述阿司匹林抵抗的可能机制.     

阿司匹林抵抗

研究表明在接受阿司匹林治疗的心血管疾病患者中有5％～45％存在阿司匹林抵抗，由于全球有大量的患者依赖阿司匹林的抗血小板治疗，所以关于阿司匹林抵抗的研究已经引起广泛关注。本文综述阿司匹林抵抗的可能机制。     

Aspirin and clopidogrel resistance: an emerging clinical entity.

Antiplatelet therapy is a cornerstone of cardiovascular medicine. Aspirin and clopidogrel have emerged as critical therapies in the treatment of cardiovascular disease. Despite their efficacy, patients on these medications continue to suffer complications. Millions of patients are currently on low-dose antiplatelet therapy but it is unknown how many of these patients are under-treated or on the wrong medication. Aspirin and clopidogrel resistance are emerging clinical entities with potentially severe consequences such as recurrent myocardial infarction, stroke, or death. The mechanism of resistance remains incompletely defined, but there are specific clinical, cellular, and genetic factors that influence therapeutic failure. These factors range from physicians who fail to prescribe these medications despite appropriate indications to polymorphisms of platelet membrane glycoproteins. Rapid and accurate diagnosis of antiplatelet resistance also remains an issue as new bedside tests are developed. By understanding the mechanism of therapeutic failure and by improving the diagnosis of this clinical entity, a new era of individualized antiplatelet therapy may arise with routine measurements of platelet activity in the same way that cholesterol, blood pressure, and blood sugar are followed, thus improving the care for millions of people.     

氯吡格雷抵抗的药物基因组学研究进展

目前,氯吡格雷联合阿司匹林双重抗血小板是治疗急性冠状动脉综合征和经皮冠状动脉介入术后抗栓的基础药物。然而,氯吡格雷抗血小板作用的反应存在个体差异,氯吡格雷抵抗现象日益受到关注。但氯吡格雷抵抗的机制仍不完全清楚,明确抵抗的原因和机制将使冠状动脉疾病患者受益匪浅。现就氯吡格雷抵抗的定义、检测方法、可能机制及药物基因组学进行综述。     

Can platelet function tests predict the clinical efficacy of aspirin?

"Aspirin resistance" and "aspirin nonresponsiveness" are terms used both to describe both the failure of aspirin to protect subgroups of individuals from severe vascular events and to evoke an appropriate inhibition of platelet function. Several studies utilizing a broad range of platelet function tests have shown that some subgroups of individuals exhibit a reduced or completely missing antiplatelet response to aspirin. The clinical significance of aspirin nonresponsiveness for the prediction of clinical endpoints remains, however, to be determined. Thus far, only three prospective clinical trials have demonstrated a possible relationship between aspirin nonresponsiveness and subsequent vascular events. Most platelet function tests used in respective clinical studies cannot be reliably performed in clinical routine and are not interchangeable for monitoring antiplatelet treatment. There is a need for a simple and reliable assay for predicting the clinical efficacy of antiplatelet therapy. Recent data demonstrate that none of the currently developed assays, including the PFA-100 system, are presently able to accomplish these objectives.     

心血管病患者中的阿司匹林抵抗

目的　前瞻性地评价心血管病患者发生阿司匹林抵抗 (AR)的流行病学概况 ,并探讨其预测因子。方法　 35 2例病情稳定的心血管病住院患者 ,每日服用阿司匹林 10 0mg ,连服 7天 ,服用最后一剂后 2 4h内抽取的空腹静脉血为血样 ,分别用二磷酸腺苷 (ADP)、花生四烯酸 (AA)诱导血小板凝集试验 (PAgT) ,检测血小板聚集率。结果　患者中AR发生率为 3.98% ,阿司匹林半敏感 (ASR)者占 2 5 .9% ,且AR或ASR患者中的女性较AS者多(35 .2 %vs 18.2 % ,P =0 .0 0 1) ,而AS者中吸烟者较AR或ASR者多 (0 %vs 9.5 % ,P =0 .0 0 2 )。结论　阿司匹林用于抗血小板治疗及预防动脉硬化事件的心血管病患者 ,若有AR存在可选择其他安全有效的抗血小板制剂长期服用 ,预测AR及抗血小板治疗个体化 ,将是抗血小板治疗未来的方向     

Antiplatelet resistance with aspirin and clopidogrel: Is it real and does it matter?

Platelets play a pivotal role in the pathophysiology of ischemic complications of atherosclerotic cardiovascular disease. Aspirin and clopidogrel are oral antiplatelet drugs that have been shown to reduce adverse clinical events across the wide spectrum of patients with atherothrombotic disease. However, recurrent ischemic events still occur in a significant proportion of patients despite treatment with these antiplatelet drugs. The concept of antiplatelet resistance therefore emerges. Although uniform definitions and standardized assays are not yet available, numerous studies have documented the interindividual variability in platelet responsiveness to oral antiplatelet drugs. Evidence is also accumulating to demonstrate that hyporesponsiveness to antiplatelet drugs in the laboratory (ie, resistance) is associated with adverse clinical events in different patient populations. Clinical application of antiplatelet resistance will require proof from prospective randomized trials that modifications of antiplatelet therapy based on tests of antiplatelet responsiveness will improve the outcomes of patients with antiplatelet resistance.     

Antiplatelet Therapy and Coronary Artery Bypass Grafting: Analysis of Current Evidence With a Focus on Acute Coronary Syndrome

This review was undertaken to summarize and discuss the current evidence around antiplatelet therapy and coronary artery bypass grafting (CABG). Aspirin (ASA) monotherapy remains the standard of care among patients before and after CABG. The role of more intense antiplatelet therapy—specifically, P2Y12 inhibitors—in improving clinical outcomes and graft patency is becoming increasingly apparent. As such, we provide an overview of a variety of antiplatelet regimens. The review discusses the evidence around preoperative management of antiplatelet therapies, with a particular focus on timing of cessation. It also evaluates the current literature to elucidate the best antiplatelet therapy regimen after CABG, focusing on acute coronary syndrome (ACS). Whenever possible, data are presented from randomized controlled trials (RCTs) and meta-analyses. Although guidelines recommend use of dual antiplatelet therapy (DAPT) after CABG for patients with ACS, available evidence is limited to small RCTs, and meta-analyses are of substudies of larger RCTs. There is also considerable heterogeneity in patient population of these studies; a significant number of patients underwent off-pump CABG (OPCAB) in trials that demonstrate graft-patency benefit with DAPT. With this limited evidence, DAPT remains underused in the CABG population, even among patients presenting after ACS.     

阿司匹林抵抗与缺血性脑血管事件

阿司匹林为缺血性脑血管病的一级和二级预防用药,但长期服用仍有可能发生动脉血栓形成事件,此即阿司匹林抵抗(asprin resistance,AR)现象.目前尚缺乏诊断AR的金标准,通常理解为阿司匹林抗血小板聚集生物学效应和预防脑血栓形成事件作用的丧失.一旦发生AR,应及时换用其他安全有效的抗血小板药.文章对AR的概念、流行病学、发生机制、检测方法和临床干预等进行了综述.     

Investigational antiplatelet drugs for the treatment and prevention of coronary artery disease

Antiplatelet therapy for the prevention and treatment of coronary artery disease (CAD) has undergone dramatic changes and improvements. Aspirin remains the first-line antiplatelet drug for clinical use. Newer platelet inhibitors such as the thienopyridine agents, ticlopidine and clopidogrel, have also been shown to be effective in treating CAD. There have been ongoing efforts to evaluate newer antiplatelet drugs, with the potential to improve clinical efficacy and safety. Some of the more promising antiplatelet agents include new adenosine diphosphate receptor antagonists such as prasugrel, cangrelor, and ticagrelor (AZD6140). In addition, a new thromboxane receptor antagonist, NCX-4016, a newly discovered protease-activated receptor antagonist that targets thrombin-induced platelet aggregation, and anti-von Willebrand factor aptamers show tremendous promise in refining antiplatelet therapy by targeting different receptors and molecules.     

The role of aspirin in cardiovascular prevention: implications of aspirin resistance

Aspirin is well recognized as an effective antiplatelet drug for secondary prevention in subjects at high risk of cardiovascular events. However, most patients receiving long-term aspirin therapy still remain at substantial risk of thrombotic events due to insufficient inhibition of platelets, specifically via the thromboxane A2 pathway. Although the exact prevalence is unknown, estimates suggest that between 5.5% and 60% of patients using this drug may exhibit a degree of "aspirin resistance," depending upon the definition used and parameters measured. To date, only a limited number of clinical studies have convincingly investigated the importance of aspirin resistance. Of these, few are of a sufficient scale, well designed, and prospective, with aspirin used at standard doses. Also, most studies do not sufficiently address the issue of noncompliance to aspirin as a frequent, yet easily preventable cause of resistance to this antiplatelet drug. This review article provides a comprehensive overview of aspirin resistance, discussing its definition, prevalence, diagnosis, and therapeutic approaches. Moreover, the clinical implications of aspirin resistance are explored in various cardiovascular disease states, including diabetes mellitus, hypertension, heart failure, and other similar disorders where platelet reactivity is enhanced.