阿司匹林和氯吡格雷抵抗

阿司匹林通过不可逆抑制环氧合酶（COX）-1,阻止花生四烯酸代谢产物血栓素A2（TXA2）形成,从而发挥其抑制血小板聚集作用.汇总分析表明,接受阿司匹林治疗的高危患者血管性事件（包括心肌梗死、卒中或死亡）发生率降低25%～30%,但是仍有10%～20%的患者5年内再发血管性事件.     

Aspirin and clopidogrel resistance: an emerging clinical entity.

We read with interest the recent article which reviewed theissue of aspirin and clopidogrel resistance.¹ The authors reviewthe aspirin and clopidogrel clinical trial data and concludethat both therapies have emerged as efficacious in both theprimary and     

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.     

Aspirin and clopidogrel resistance in patients with diabetes mellitus.

We read with interest the review paper on aspirin and clopidogrelresistance by Wang et al.¹ We agree that it is an emergingentity with important clinical implications. Nevertheless, wewere surprised that very little emphasis was put on the antiplateletagent resistance of diabetic patients. Only one     

症状性颈动脉和椎-基底动脉狭窄患者的阿司匹林和氯吡格雷抵抗现象

目的观察症状性颈动脉和椎-基底动脉狭窄患者服用阿司匹林和氯吡格雷抵抗现象的发生情况。方法在54例症状性的颈动脉(25例)、椎动脉(19例)、颈动脉合并椎动脉(8例)以及基底动脉(2例)狭窄的患者中,有39例行择期支架置入术。采用二磷酸腺苷、肾上腺素、胶原和花生四烯酸为诱导剂,分别测定已服用阿司匹林(100mg/d)≥10d,以及随后加服氯吡格雷(75mg/d)≥5d患者的血小板聚集率。阿司匹林抵抗标准为单用阿司匹林时,以500μg/ml花生四烯酸诱导的血小板聚集率≥20%和5μmol/L二磷酸腺苷诱导的血小板聚集率≥70%。氯吡格雷抵抗标准为在阿司匹林基础上加用氯吡格雷前、后,5μmol/L二磷酸腺苷诱导血小板聚集率的差值≤10%。结果54例患者中,有9例(16.7%)存在阿司匹林抵抗,12例(22.2%)存在氯吡格雷抵抗,1例(1.8%)存在阿司匹林和氯吡格雷双抵抗。9例阿司匹林抵抗者加用氯吡格雷后有5例花生四烯酸诱导的聚集率降至<20%,有8例二磷酸腺苷诱导的聚集率降至<70%。1例支架置入术后支架内急性血栓形成为阿司匹林抵抗的患者。结论症状性颈动脉和椎-基底动脉狭窄患者中存在一定比例的阿司匹林或氯吡格雷抵抗现象,氯吡格雷与阿司匹林合用克服了部分阿司匹林抵抗现象。阿司匹林抵抗可能与支架置入术后血栓性并发症的增加有关。     

Aspirin and clopidogrel: a sweeping combination in cardiology

Platelets play a pivotal role in the pathogenesis of atherothrombosis, believed to be integrally involved in both the development and progression of atherosclerotic heart disease, as well as in its acute thrombotic complications. Antiplatelet therapy constitutes the cornerstone in the management of patients with acute coronary syndromes and generally high-risk patients with atherothrombosis. Until recently, long-term antiplatelet therapy for the treatment and prevention of the complications of atherothrombotic disease was traditionally limited to aspirin. The availability of the thienopyridines, in particular clopidogrel, represents an important addition to the physician's armamentarium. Clopidogrel is currently one of the most widely prescribed drugs for the treatment of symptomatic coronary artery disease. Aspirin and clopidogrel interfere with platelet activation in complementary, but separate pathways. Aspirin irreversibly inhibits cyclooxygenase, thus preventing the production of thromboxane A(2), which is a prothrombotic and vasoconstrictive substance. Clopidogrel, a newer thienopyridine which has largely supplanted ticlopidine due to a more favorable safety profile, irreversibly prevents platelet activation by blocking one of the three known adenosine 5'-diphosphate (ADP) receptors (the P2Y(12) receptor) on the platelet surface, thus interfering with platelet activation, degranulation and aggregation. Both these antiplatelet agents have a potent protective effect against adverse vascular events, but the combination of these two agents has an even stronger antiplatelet effect translating into superior antithrombotic protection in coronary, cerebral or peripheral arterial disease, without an inordinate increase in bleeding complications. A number of seminal clinical trials have demonstrated and confirmed the incremental benefit and efficacy of the combination of clopidogrel and aspirin therapy above and beyond that of aspirin alone, with multiple other important large-scale clinical trials currently ongoing. Newer data are being accumulated from studies where indications for the use of clopidogrel and aspirin continue to expand into other patient groups, rendering this dual antiplatelet drug therapy a sweeping combination in Cardiology. However, important issues remain to be further and more thoroughly explored about the benefit of this antiplatelet drug combination in these other patient groups, such as in patients with heart failure, where preliminary data indicate a favorable effect on thrombotic vascular events, in patients with atrial fibrillation, where there is hope that this combination may replace or be an alternative treatment modality to coumadin in certain subpopulations, in patients undergoing demanding catheter ablation procedures, where data point to a protective effect from thromboembolic events. Another pertaining issue to be further investigated is the occurrence of drug-resistance observed in some patients for both these antithrombotic agents. This article is a comprehensive review of all these data and the landmark trials on the two antiplatelet agents, the issues involved and the current recommendations for their use in patients with atherosclerotic heart disease and other cardiovascular disorders and procedures.     

Aspirin and clopidogrel response variability: review of the published literature

Antiplatelet resistance has been proposed as a possible mechanism to explain recurrent cardiovascular events in patients who have coronary artery disease and who are undergoing dual antiplatelet therapy. A comprehensive search on PubMed was conducted for literature that was printed in the English language between January 1996 and November 2007 on aspirin and clopidogrel resistance. Significant traits for aspirin hyporesponsiveness were female sex, older age, and lower levels of hemoglobin. Diabetes mellitus and elevated body mass index showed trends toward a higher incidence of resistance in some aspirin trials but did not reach statistical significance. Clopidogrel studies suggested that patients with type-2 diabetes mellitus are more likely to manifest inadequate response to the medication. Although 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors were initially suspected to decrease response to clopidogrel, later studies refuted this possibility. Patients with a suboptimal response to aspirin or clopidogrel seem to be at increased risk of recurrent cardiovascular events. Large clinical trials with standardized laboratory methods and well-defined protocols are needed to determine whether common features exist in patients with suspected hyporesponsiveness to antiplatelet therapy, and to validate the clinical relevance of response variability. A concise nonarbitrary definition of physiologic "resistance" is needed, and investigators should identify patients as having a variable response to antiplatelet therapy.     

阿司匹林抵抗

阿司匹林能有效预防缺血性脑血管病,但由于"阿司匹林抵抗"现象的存在,仍有部分患者在阿司匹林治疗期间发生缺血事件.文章主要对阿司匹林抵抗的机制、筛查方法 和处理措施进行了综述.     

Aspirin and clopidogrel drug response in patients undergoing percutaneous coronary intervention: the role of dual drug resistance.

We evaluated the response to clopidogrel among aspirin-resistant versus aspirin-sensitive patients undergoing elective coronary stenting. Patients (n = 150) treated with aspirin but not clopidogrel had blood samples drawn at baseline and 24 h after clopidogrel loading. Depending on the definition used, 9% to 15% were resistant to aspirin and 24% to clopidogrel. About half of the aspirin-resistant patients were also resistant to clopidogrel. As a group, aspirin-resistant patients had lower response to clopidogrel (assessed by platelet aggregation and activation markers) than aspirin-sensitive patients. Both aspirin- and clopidogrel-resistant patients had higher incidence of creatine kinase-MB elevation than the respective sensitive patients. OBJECTIVES: We sought to evaluate the response to clopidogrel among aspirin-resistant versus aspirin-sensitive patients undergoing percutaneous coronary intervention (PCI). BACKGROUND: Wide variability has been reported in response to aspirin and clopidogrel. There are limited data on the simultaneous responses to both drugs. METHODS: Elective PCI patients (n = 150) who received aspirin for > or = 1 week but not clopidogrel were included. All patients received bivalirudin during PCI. Blood samples were drawn at baseline and 20 to 24 h after a 300-mg clopidogrel dose. Aspirin resistance was defined by > or = 2 of 3 criteria: rapid platelet function analyzer-ASA score > or = 550, 5 micromol/l adenosine diphosphate (ADP)-induced aggregation > or = 70%, and 0.5 mg/ml arachidonic acid-induced aggregation > or = 20%. Clopidogrel resistance was defined as baseline minus post-treatment aggregation < or = 10% in response to 5 and 20 micromol/l ADP. RESULTS: Nineteen (12.7%) patients were resistant to aspirin and 36 (24%) to clopidogrel. Nine (47.4%) of the aspirin-resistant patients were also clopidogrel resistant. Aspirin-resistant patients were more likely to be women and have diabetes than were aspirin-sensitive patients. They also had lower response to clopidogrel, assessed by platelet aggregation and activation markers (flow cytometry-determined PAC-1 binding and P-selectin expression). Elevation of creatine kinase-myocardial band after stenting occurred more frequently in aspirin-resistant versus aspirin-sensitive patients (38.9% vs. 18.3%; p = 0.04) and in clopidogrel-resistant versus clopidogrel-sensitive patients (32.4% vs. 17.3%; p = 0.06). CONCLUSIONS: Aspirin-resistant patients as a group have reduced response to clopidogrel. Furthermore, we have identified a unique group of dual drug-resistant patients who may be at increased risk for thrombotic complications after PCI.     

阿司匹林抵抗

自20世纪70年代起,阿司匹林作为抗血小板药物广泛用于心血管疾病的预防和治疗,大量循证医学证据证实心脑血管疾病高危患者应用阿司匹林,可使心脑血管事件如心肌梗死、脑卒中降低25%。但是,近年研究发现仍有部分服用阿司匹林的患者不能充分抑制血小板功能而致临床血栓事件的发生     

Aspirin resistance

Aspirin resistance is the inability of aspirin to reduce platelet production of thromboxane A2 and thereby platelet activation and aggregation. Increasing degrees of aspirin resistance may correlate independently with increasing risk of cardiovascular events. Aspirin resistance can be detected by laboratory tests of platelet thromboxane A2 production or platelet function that depend on platelet thromboxane production. Potential causes of aspirin resistance include inadequate dose, drug interactions, genetic polymorphisms of COX-1 and other genes involved in thromboxane biosynthesis, upregulation of non-platelet sources of thromboxane biosynthesis, and increased platelet turnover. Aspirin resistance can be overcome by treating the cause or causes, and reduced by minimising thromboxane production and activity, and blocking other pathways of platelet activation. Future research is aimed at defining aspirin resistance, developing reliable tests for it, and establishing the risk of associated cardiovascular events. Potential mechanisms of aspirin resistance can then be explored and treatments assessed.     

Aspirin resistance: An update

Aspirin resistance (AR) still lacks a universally accepted definition, but it may be discussed as either a laboratory phenomenon or a clinical presentation. Laboratory resistance is mainly defined as abnormal platelet response to aspirin, whereas the clinical manifestation is the failure of aspirin to prevent cardiovascular events. Although there is evidence of an association, it appears that a laboratory abnormality in platelet function is not the only risk factor for the clinical manifestation of AR. Therapies for primary and secondary prevention of AR still need to be elucidated, but there are some data to suggest that in an acute episode of aspirin failure because of AR, different therapeutic interventions need to be considered.     

Aspirin resistance: mechanisms and clinical implications

Acetylsalicylic acid (aspirin) has been shown to irreversibly interfere with platelet function, an effect that is associated with a reduction in morbid and mortal arterial thrombotic events in multiple clinical studies. This clinical benefit appears to be attenuated by resistance to the antiplatelet effects of aspirin in up to 35% of patients. The mechanisms for aspirin resistance are multifactorial and include noncompliance with aspirin therapy, diabetes mellitus, cell-cell and drug-drug interactions, genetic polymorphisms, and coronary artery disease. It has not been determined what the best laboratory procedure is to screen for aspirin resistance. Those individuals at high risk for aspirin resistance might best be treated with an additional oral antiplatelet drug (eg, clopidogrel) to achieve maximal protection against arterial thrombotic events.