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。     

阿司匹林抵抗的研究进展

阿司匹林通过不可逆地乙酰化环氧化酶-1,在心血管疾病的防治中发挥着重要作用.但部分患者存在阿司匹林抵抗现象,其发生机制尚未明确,可能与药物剂量、依从性、基因多态性等有关.实验室检测阿司匹林抵抗的方法有光学聚集法、全血电阻抗法、血栓素的测定等.研究证实阿司匹林抵抗与临床事件的发生具有相关性.因此,将来有待进一步研究阿司匹林抵抗的相关机制、检测方法及防治策略,旨在相关临床事件发生之前筛选出抵抗患者,从而优化抗血小板药物治疗.     

阿司匹林抵抗相关研究进展

阿司匹林抵抗描述了导致阿司匹林在预防血栓并发症、引起出血时间延长、体外抑制血小板聚集以及抑制血小板血栓素形成等方面效力降低的多种不同现象。通过生化方法测定,我们将阿司匹林抵抗分为三种不同类型,此种分型有助于阐述阿司匹林抵抗的机制,包括药物剂量不足、血小板周转加快、药物依从性差、相关基因多态性以及血栓素非经血小板旁路途径形成等。     

阿司匹林抵抗的临床与实验研究进展

阿司匹林抵抗的可能原因包括低依从性、药物交叉反应、药物剂量不足、血小板周转加快、相关基因多态性以及血栓素非经血小板旁路途径形成等.现有的针对阿司匹林抵抗的实验室方法包括对TXA2及其代谢产物的检测和血小板功能的测定,临床上应采取措施减少阿司匹林抵抗以取得理想的预防和治疗效果.     

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。     

氯吡格雷抵抗机制的新认识

氯吡格雷是目前广泛应用的抗血小板药物之一.氯吡格雷抵抗的确切机制迄今尚未完全阐明.其可能机制包括基因多态性、血小板活化因素、生物利用度差异、胰岛素抵抗与阿斯匹林抵抗因素、依从性与剂量因素及药物相互作用等.氯吡格雷抵抗的出现,已影响其疗效的发挥,该文就近年来氯吡格雷抵抗机制的新进展、新认识和防治策略作一综述.     

阿司匹林抵抗

阿司匹林抵抗是指阿司匹林不能：（1）保护服用者不发生血栓性并发症;（2）延长出血时间;（3）抑制血栓素的生物合成或（4）在体外试验中对血小板功能发挥预期影响.阿司匹林抵抗的可能机制包括：（1）5%～40%的缺血性血管病并非动脉粥样硬化所致;（2）依从性差或剂量不足.阿司匹林抵抗尚无特异性治疗方法.对于不能耐受阿司匹林或出现阿司匹林抵抗的患者,应选择ADP受体拮抗剂氯吡格雷或其他抗血小板药治疗.     

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.     

阿司匹林抵抗的产生机制及防治对策．

阿司匹林防治心脑血管血栓性疾病已经在临床上广泛应用,可减少大约25％的心脑血管事件的发生。但临床上有8％-60％的患者常规服用阿司匹林,其血小板聚集能力不能被很好的抑制,临床上称这种现象为阿司匹林抵抗（AR）。产生AR现象的原因还不明确,可能与药物问的相互作用、剂量不足等有关。     

Narrative review: aspirin resistance and its clinical implications

Aspirin is currently the most cost-effective drug for the secondary prevention of cardiovascular disease, but treatment failures are relatively common. Several factors have been linked to these recurrent vascular events in patients prescribed aspirin, including smoking, drug interactions, nonadherence, comorbid conditions, and aspirin resistance. The term aspirin resistance has been used to describe not only an absence of the expected pharmacologic effects of aspirin on platelets but also poor clinical outcomes, such as recurrent vascular events, in patients treated with aspirin. Aspirin resistance is perhaps more precisely understood as the phenomenon of measurable, persisting platelet activation that occurs in patients prescribed a therapeutic dose of aspirin and may underlie an unknown proportion of aspirin treatment failures. Key challenges for future research are to standardize a definition of aspirin resistance and to compare whether different measures of platelet activation, either alone or in combination, independently predict cardiovascular events. These challenges must be met before researchers conduct studies to assess the clinical utility of testing on patient outcomes and cost-effective prescribing.     

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: 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.     

Aspirin and clopidogrel resistance: consideration and management

The efficacy with aspirin and clopidogrel treatment has been demonstrated in various clinical trials. Laboratory evaluation of platelet response in recent studies revealed that a distinctive response variability and nonresponsiveness/resistance in selected patients were associated with these antiplatelet agents. Moreover, some studies have correlated this nonresponsiveness/resistance phenomenon to the occurrence of thrombotic events. At this time there are no uniformly established methods to quantify exvivo platelet reactivity after clopidogrel and aspirin treatment of the extent of platelet inhibition by clopidogrel and aspirin. Therefore, specific treatment recommendations for patients exhibiting high platelet reactivity or poor platelet inhibition during clopidogrel or aspirin therapy are not established. A higher aspirin dose and strict compliance to therapy may overcome the occurrence of "aspirin resistance" in selected patients. A higher clopidogrel dose may be considered in patients exhibiting clopidogrel nonresponsiveness.     

Acid-NSAID/aspirin interaction in peptic ulcer disease

The presence of gastric acid plays a critical role in the mechanisms of NSAIDs/aspirin-associated gastric and duodenal mucosal injury and ulceration. The role of gastric acid and its relationship to NSAIDs/aspirin in mucosal damage, ulcer and ulcer complications continues to be an important concern because of the increasing worldwide use of NSAIDs and aspirin. Acid suppression continues to be an important prevention strategy for NSAID-associated gastric and duodenal ulcer and ulcer complications. While a coxib or an NSAID and PPI in combination are considered to have comparable safety profiles, the evidence from direct comparisons in high-risk patients is limited, and the cardiovascular safety of coxibs and NSAIDs remains a concern especially in patients with a high risk of cardiovascular disease. An evaluation of individual gastrointestinal and cardiovascular risks and benefits, selection of the most appropriate NSAID and dose for each particular patient should always be emphasized. Twice daily PPI is more appropriate to protect a patient who is taking NSAIDs twice daily. PPI co-therapy is still recommended in patients receiving dual antiplatelet treatment, although conflicting results have been reported about adverse drug interactions between PPIs and clopidogrel.     

阿司匹林抵抗

阿司匹林抵抗是指阿司匹林不能:(1)保护服用者不发生血栓性并发症;(2)延长出血时间;(3)抑制血栓素的生物合成或(4)在体外试验中对血小板功能发挥预期影响。阿司匹林抵抗的可能机制包括:(1)5%～40%的缺血性血管病并非动脉粥样硬化所致;(2)依从性差或剂量不足。阿司匹林抵抗尚无特异性治疗方法。对于不能耐受阿司匹林或出现阿司匹林抵抗的患者,应选择ADP受体拮抗剂氯吡格雷或其他抗血小板药治疗。     

阿司匹林抵抗的研究现状

阿司匹林抵抗即阿司匹林不能减少血小板血栓素A2的生成并因此引起血小板活化和聚集。阿司匹林抵抗的可能原因包括用量不当、药物相互作用、环氧合酶-1的遗传多态性和涉及血栓素生物合成的其他基因、血栓素生物合成的非血小板源性因素的上调和血小板更新增强。阿司匹林抵抗程度的增强可能与心血管事件风险的增加独立相关。目前还没有一种精确定性和定量分析的方法来检测阿司匹林的抗血小板功能异常,从而解释生物化学的阿司匹林抵抗。今后的研究旨在准确定义阿司匹林抵抗、开发可靠的检测方法并确定相关心血管事件的发生风险。     

Low-dose aspirin in patients with diabete melitus: risks and benefits regarding macro and microvascular complications

Aspirin is recommended as cardiovascular disease prevention in patients with diabetes mellitus. Due to the increased risk of bleeding and because of the hypothesis that there could be a worsening of microvascular complications related to aspirin, there has been observed an important underutilization of the drug. However, it is now known that aspirin is not associated with a deleterious effect on diabetic retinopathy and there is evidence indicating that it also does not affect renal function with usual doses (150 mg/d). On the other hand, higher doses may prove necessary, since recent data suggest that diabetic patients present the so called "aspirin resistance". The mechanisms of this resistance are not yet fully understood, being probably related to an abnormal intrinsic platelet activity. The employment of alternative antiplatelet strategies or the administration of higher aspirin doses (150-300 mg/d) should be better evaluated regarding effective cardiovascular disease prevention in diabetes as well as the possible effects on microvascular complications.