阿司匹林抵抗与缺血性脑卒中的研究进展

缺血性脑卒中作为目前中老年人高发疾病之一,其首选阿司匹林抗血小板聚集的防治手段已得到国内外认可。但部分患者服用阿司匹林后仍出现阿司匹林抵抗的现象。现阶段关于阿司匹林抵抗的机制复杂且多样,使其在缺血性脑卒中患者中的发生率逐年增加。因此,在缺血性脑卒中患者中加深对阿司匹林抵抗的认识及掌握阿司匹林抵抗的相关防治措施至关重要。     

氯吡格雷/阿司匹林双抗预防非心源性缺血性脑卒中的效果观察

目的观察氯吡格雷联合阿司匹林双抗防治非心源性缺血性脑卒中的临床效果。方法选取2011-05—2014-05收治的非心源性缺血性脑卒中患者114例,随机分为观察组与对照组,2组均常规卒中治疗,在此基础上对照组单纯应用阿司匹林,观察组使用氯吡格雷联合阿司匹林治疗,观察2组临床效果。结果观察组3个月、1a内复发率均明显低于对照组,总不良反应率低于对照组,差异均有统计学意义(P0.05)。结论对非心源性缺血性脑卒中患者使用氯吡格雷联合阿司匹林进行双抗防治,能够有效降低其卒中复发率,减少不良反应,在临床防治中有较理想的效果。     

通心络与阿司匹林预防再次缺血性脑卒中的作用

目的观察通心络胶囊在预防再次缺血性脑卒中的作用，并与阿司匹林对比。方法将128例急性脑梗死患者随机分为两组：通心络胶囊组62例，阿司匹林组66例，观察两组患者服药期间缺血性卒中的再发生、死亡及不良反应等临床表现。结果两组比较缺血性脑卒中的人数分别为通心络组6例，阿司匹林组8例，虽然通心络组比阿司匹林组发生人数少，但两组比较无统计学差异（P〉0．05）。两组不良反应比较通心络组为4例，阿司匹林组12例，差异有统计学意义（P〈0．05）。结论通心络胶囊预防再次缺血性脑卒中与阿司匹林有同样的作用，但阿司匹林组有较多的不良反应。     

阿司匹林对缺血性脑卒中二级预防的前瞻性分析

在我国,30万居民的流行病学调查结果估计,每年新发脑卒中为120万～150万人,死于脑卒中的为80万～100万人,其中50%是缺血性脑卒中[1].目前缺乏有效的治疗手段,故预防显得尤为重要,我们采用阿司匹林对缺血性脑卒中进行二级预防前瞻性研究,报告如下.     

阿司匹林在防治心脑血管疾病中的性别差异

循证医学研究证实,阿司匹林对心脑血管病的防治有肯定的价值.阿司匹林作为抗血小板聚集药物,降低缺血性血管事件的作用机制是抑制血小板中花生四烯酸环氧化酶1(COX1),减少血栓素A2(TXA2)生成,从而抑制血小板释放二磷酸腺苷(ADP)和血小板聚集的激活.     

阿司匹林在脑卒中一级预防中的应用

阿司匹林对脑卒中二级预防的效果已经确定,但其在脑卒中一级预防中的获益和风险仍存在较大争议。基于现有的临床证据,仅部分人群从阿司匹林一级预防措施中获益,本文结合相关脑卒中一级预防指南和主要文献,就阿司匹林在脑卒中一级预防中的应用依据、作用机制、适用人群及风险评价等简要概述。     

阿司匹林在防治心脑血管疾病中的性别差异

循证医学研究证实，阿司匹林对心脑血管病的防治有肯定的价值。阿司匹林作为抗血小板聚集药物，降低缺血性血管事件的作用机制是抑制血小板中花生四烯酸环氧化酶1（COX1），减少血栓素A2（TXA2）生成，从而抑制血小板释放二磷酸腺苷（ADP）和血小板聚集的激活。由于血小板无细胞核，不能生成新的COX，所以阿司匹林的这种作用不可逆。小剂量阿司匹林不可逆地乙酰化COX而抑制TXA2形成，并不抑制内皮细胞前列腺素（PG）合成，故不会对血管舒张功能造成影响。目前，阿司匹林被广泛应用于缺血性血管疾病防治。     

小剂量阿司匹林联合氯吡格雷治疗缺血性脑血管病疗效观察

缺血性脑血管病是目前主要的致死、致残性疾病之一,其高复发率是导致预后差,病死率高的主要原因,因此,加强缺血性脑血管病的二级预防是降低其致死、致残率的关键。抗血小板聚集药物在缺血性脑血管病中防治中的作用已得到公认。我们应用小剂量阿司匹林联合氯吡格雷治疗缺血性脑血管病23例,现报告如下。1对象与方法1.1对象2008-01～2010-06在科住院的缺血性脑血管病患者45例,符合全国第四届脑血管病学术会议修订的诊断标准,经头颅CT或MRI证实,排除标准:无严重肝、肾功     

肿瘤坏死因子-α对缺血性脑卒中的作用

缺血性脑卒中是中老年常见疾病,因其病理机制复杂,临床体征多变,现临床治疗效果仍不理想,肿瘤坏死因子-α在其发生发展过程中起到重要作用,临床如果能够利用好它的作用,促进其有益作用,抑制其有害作用,将为缺血性脑卒中的防治打开新的思路,因此,本文对肿瘤坏死因子-α在缺血性脑卒中进展中的作用进行了综述。     

缺血性脑卒中患者阿司匹林或氯吡格雷及其联合应用抗血小板治疗的研究

目的 研究缺血性脑卒中患者阿司匹林或氯吡格雷及其联合应用抗血小板治疗的效果.方法 180例缺血性脑卒中患者分为阿司匹林组(阿司匹林肠溶片100 mg/d)、氯吡格雷组(氯吡格雷75 mg/d)和联合用药组(阿司匹林肠溶片+氯吡格雷,剂量相同);每组60例.在治疗前、治疗14 d后,用血栓弹力图检测患者的花生四烯酸(AA)和二磷酸腺苷(ADP)途径诱导的血小板抑制率.结果 治疗后,3组AA、ADP途径诱导的血小板抑制率显著高于治疗前(均P＜0.05);3组间AA、ADP途径诱导的血小板抑制率的差异有统计学意义(均P＜0.05).联合用药组和阿司匹林组AA途径诱导的血小板抑制率显著高于氯吡格雷组(均P＜0.05);联合用药组和氯吡格雷组ADP途径诱导的血小板抑制率显著高于阿司匹林组(均P＜0.05);联合用药组与阿司匹林组AA途径、联合用药组与氯吡格雷组ADP途径诱导的血小板抑制率的差异无统计学意义.结论 阿司匹林和氯吡格雷对缺血性脑卒中患者均有显著的抗血小板作用;而阿司匹林联合氯吡格雷能从两个途径抑制血小板聚集,抗血小板的效果更好.     

Aspirin resistance

Aspirin resistance refers to less than expected suppression of thromboxane A(2) production by aspirin and has been reported to be independently associated with an increased risk of adverse cardiovascular events. Possible causes of aspirin resistance include poor compliance, drug interaction, inadequate aspirin dose, increase turnover of platelets, genetic polymorphisms of cyclo-oxygenase-1, and upregulation of alternate (non-platelet) pathways of thromboxane production. Laboratory methods used to detect aspirin resistance include those that measure thromboxane A(2) production and thromboxane A(2)-dependent platelet function. However, since there is currently no standardised approach to the diagnosis and there are no proven effective treatments for aspirin resistance that improve outcome, patients with cardiovascular disease receiving aspirin should not be routinely tested for aspirin resistance. Instead physicians should be aware of the factors that may impair aspirin function, ensure that they use an appropriate dose of aspirin and optimise compliance with aspirin therapy. Further research exploring the mechanisms of aspirin resistance is needed in order to better define and develop a standardised test for aspirin resistance that is specific, reliable, can be readily applied in routine laboratories and correlate with an increased risk of cardiovascular events.     

阿司匹林抵抗

阿司匹林是百年老药，最初主要用于疼痛或炎症的治疗，二十世纪六十年代以后发现阿司匹林有较好的抗血栓作用而被广泛用于防治心脑血管病。抗血小板试验联合报告的结论：（1）阿司匹林应用于心脑皿管疾病高危患者可以降低25％心脑皿管病事件如死亡、心肌梗死、卒中；（2）降低48％的血管搭桥及动脉栓塞事件；（3）减少67％的肺栓塞事件和67％的深静脉血栓事件。     

Aspirin resistance theory

Acetylsalicylic acid is an effective antiplatelet drug for primary and secondary prevention of heart and brain vascular diseases. Analyses of trials including patients with atherosclerosis proved that vascular ischaemic events have been reduced by 25% and risk of vascular death has been reduced due to aspirin. The increasing number of reports about aspirin resistance (the failure of the compound to protect from an ischemic event despite regular intake of appropriate doses) is alarming. The purpose of this review is to present current opinions and results of investigations connected with this problem.     

Aspirin and human sleep

Two groups of 8 females were given either 3 X 600 mg aspirin or placebo daily for 4 days, double blind. With aspirin, slow wave sleep was significantly decreased and stage 2 sleep significantly increased. Aspirin also significantly disrupted intra-subject night-to-night continuity of several sleep stages during drug and recovery nights.     

Aspirin response evaluated by the VerifyNow Aspirin System and light transmission aggregometry

Introduction

Patients with inadequate platelet inhibition by aspirin, referred to as aspirin resistance, might have an increased risk of suffering cardiovascular events. Therefore, identification of these patients by measuring platelet function is of great interest. Our objectives were to evaluate performance parameters of VerifyNow™ and to determine the agreement between VerifyNow™ and light transmission aggregometry (LTA) ad modum Born.

Materials and Methods

We included 21 healthy volunteers and 40 patients with stable coronary artery disease. Duplicate measurements of platelet aggregation were performed using VerifyNow™ and LTA (arachidonic acid 1.0 mM) in healthy volunteers before aspirin and in all participants on four consecutive days during treatment with non-enteric-coated aspirin 75 mg daily. VerifyNow™ test results were expressed in Aspirin Reaction Units (ARU) and LTA test results in percent of maximal aggregation. The cut-off for determination of aspirin resistance was ≥ 550 ARU and ≥ 20%, respectively.

Results

All participants were compliant, confirmed by complete suppression of serum-thromboxane B₂. VerifyNow™ was highly repeatable with a coefficient of variance of 0.5% at baseline and 3.0% during aspirin treatment. No individuals were identified as aspirin resistant with VerifyNow™, whereas seven (12%) individuals were identified with LTA. ROC analysis using LTA as the gold standard showed poor sensitivity and good specificity with a cut-off at 550 ARU.

Conclusion

VerifyNow™ was highly repeatable, but further studies are needed to investigate the relevance of the cut-off level at 550 ARU for detecting aspirin resistance.     

Aspirin and stroke prevention

According to meta-analyses aspirin provides a relative reduction in the rate of major vascular events of 19% in patients with arterial disease in general, whereas for patients with ischaemic cerebrovascular disease this reduction is only 13%. The discrepancy may well result from pathophysiological differences and not from a play of chance. There is no proven difference in efficacy according to dose. The evidence for this equivalence is most compelling in the range between 75 and 1300 mg daily, but still fairly convincing for doses between 30 and 50 mg. In contrast, side effects are clearly more frequent as the dose is higher. Other antiplatelet agents (sulfinpyrazone, ticlopidine, clopidogrel, dipyridamole, orally administered IIb/IIIa inhibitors) have no clear advantages over aspirin and in some cases definite disadvantages; the combination of aspirin and dipyridamole may be more efficacious than aspirin alone, but the evidence hinges on a single trial. If recurrent TIAs occur under treatment with aspirin, the rational response is not to change to a different antiplatelet agent, but to review the diagnosis and consider causes other than artery-to-artery embolism. Platelet aggregation can probably still occur despite complete acetylation of platelets, via pathways other than COX-1 inhibition, but in vitro aggregation tests are an unreliable measure.