抗血小板药预防脑卒中的应用进展

以阿司匹林为代表的抗血小板药已被证实在对脑卒中预防有确实的疗效。阿司匹林、氯吡格雷等抗血小板药物作为脑卒中预防的基础用药,其疗效确切并已经列入相关脑卒中预防指南。替卡格雷、西洛他唑、三氟柳、沙格雷酯等新型抗血小板药物在部分地区的临床试验中也已经取得了令人满意的脑卒中预防结果。但是多年来,阿司匹林的最佳预防剂量仍在商榷中,在患者应用抗血小板药物的过程中,存在一定比例的出血并发症。当两种抗血小板药物合用更可能导致出血并发症的发生比例增高。寻求抗血小板药的疗效及出血并发症间的平衡点,促进抗血小板药物的进步与发展。文中就抗血小板药物在预防脑卒中的应用进展作介绍。     

Current Status of Antiplatelet Agents to Prevent Stroke

Stroke is one of the leading causes of disability; most are due to atherothrombotic mechanisms. About one third of ischemic strokes are preceded by other stroke or transient ischemic attacks. Stroke survivors are at high risk for vascular events (i.e., cerebrovascular and cardiovascular). Prevention of recurrent stroke and other major vascular events can be accomplished by control of risk factors. Nonetheless, the use of antiplatelet agents remains the fundamental component of secondary stroke prevention strategy in patients with noncardioembolic disease. Currently, the uses of aspirin, clopidogrel, or aspirin plus extended-release dipyridamole are valid alternatives for stroke or transient ischemic attack patients. To maximize the beneficial effects of these agents, the treatment should be initiated as early as possible and continue on a lifelong basis.     

Comparison of Antiplatelet Therapies for Prevention of Patent Foramen Ovale-Associated Stroke

AimsThe REDUCE study demonstrated a reduction in the risk of recurrent stroke with patent foramen ovale closure and antiplatelet therapy compared to antiplatelet therapy alone. The clinicians were allowed to choose among aspirin, clopidogrel, or aspirin/dipyridamole with the expectation that all antiplatelet therapies would have similar efficacy in this population. We tested that presumption by comparing recurrent stroke rates among antiplatelet agents within the control arm of the trial.MethodsWe evaluated patients in REDUCE study who were randomized to the medical arm. The primary endpoint for this analysis was freedom from clinical ischemic stroke through at least 2 years of follow-up, to a maximum of 5 years. In the primary analysis, antiplatelet treatment was defined as the agent during the week prior to a recurrent stroke or last known contact.ResultsOf 223 patients in the medical treatment arm, the initial agent was aspirin 52%, clopidogrel 30%, and aspirin/dipyridamole 12%. Patients treated with aspirin were similar to those treated with alternatives, but were more likely to be enrolled in the United States. The last reported agent was aspirin alone in 55%, clopidogrel alone in 31%, aspirin/dipyridamole in 7%, and other/nothing/missing in 7%. Recurrent stroke rates were similar for all 3 antiplatelet regimens in unadjusted and adjusted analyses, with no overall difference among agents (P= .17).ConclusionsAmong patients with patent foramen ovale-associated stroke who were managed medically, there were no differences among antiplatelet agents in the risk of recurrent stroke, though confidence intervals were wide.     

抗血小板治疗与短暂性脑缺血发作后的卒中预防

短暂性脑缺血发作（transient ischemic attack,TIA）是早已公认的脑缺血标志。随着新型神经影像学技术相继应用于流行病学研究和临床试验，人们发现根据症状和体征迅速消失界定TIA并不科学，而继续信守TIA为良性过程的传统观念正在严重妨碍缺血性卒中的二级预防^[1]。大量证据表明，TIA一旦发生，就意味着这些患者随时面临缺血性卒中的高危风险。因此，应像冠心病患者发生心绞痛后积极预防心肌梗死那样，对TIA患者进行及时、有效的干预，从根本上降低TIA后的卒中风险。最近，许多研究对抗血小板药用于TIA后缺血性卒中的二级预防进行了有益探讨。     

急性缺血性卒中的抗血小板治疗

急性缺血性卒中患者血小板被激活，抗血小板治疗可减少早期脑梗死的复发，减轻脑损伤的体积，降低早期死亡和改善存活者的长期预后。但抗血小板治疗增加非致死性或症状性颅内出血的发生率。阿司匹林是证据最充分且得到各国指南推荐的治疗急性缺血性卒中的抗血小板药物，对未溶栓治疗的急性缺血性卒中患者应尽早开始阿司匹林治疗。氯吡格雷、血小板糖蛋白Ⅱb/IIIa受体抑制剂、双嘧达莫、西洛他唑等单药用于治疗急性缺血性卒中的安全性和疗效目前尚无足够的证据。抗血小板药物联合应用的疗效和可能的风险尚需进一步研究。     

Lancet N：卒中二级预防长期双联抗血小板的突破

合并颈动脉和颅内动脉狭窄或多重血管危险因素的非心源性缺血性卒中患者复发风险很高。对于这一部分患者,综合预防治疗,包括抗血小板治疗,已经被证明是有益的。不过,新型抗血小板药物,比如替格瑞洛和普拉格雷,是治疗冠心病很有前景的药物,在临床应用大约10年了,但是在卒中患者的随机对照试验中并未发现它们优于传统的抗血小板药物。不同的抗血小板药物通过不同的机制发挥作用,联合用药比单药能更加有效地预防卒中。     

脑血流微栓子信号的测定在评估抗血小板药物治疗和预防动脉粥样硬化性卒中的作用

药物治疗在卒中的预防中起重要作用,用以评价卒中预防性药物药理作用传统的临床试验均以临床结局作为判断药物作用的参数,这不仅需要观察很多病例还必须观察相当长的时间,费时费钱。计算经颅多普勒超声(TCD)检测到微栓子(TCD)数量的变化可能是评价新的抗血小板药物疗效的一种新方法,更直接地评价抗血小板药物药理活性。那么,微栓子信号(MES)计数能确切地预测预防卒中的作用吗?本文回顾了已有关于MES与缺血性卒中之间的关系的研究,以及抗血小板药物对MES发生频率的影响。总体看来,越来越多的证据证实MES是脑梗死的标志物,可快速评估抗血小板药物的作用,目前正在进行的研究要进一步明确MES计数在卒中预防临床研究中的价值。     

缺血性脑卒中二级预防中的抗血小板治疗及其研究进展

抗血小板治疗是缺血性脑卒中二级预防中影响脑卒中再发率的重要因素。阿司匹林和氯吡格雷是临床常用的抗血小板药物。缺血性脑卒中二级预防中抗血小板药物的联合应用以及新药的研究已成为时下热点。由于缺血性脑卒中发病后早期再发率较高,因此早期以及长期二级预防中的抗血小板治疗方式不尽相同。     

强化抗血小板治疗在缺血性脑卒中复发高危患者二级预防中的临床研究

目的观察强化抗血小板药物氯吡格雷在缺血性脑卒中复发高危患者二级预防中的长期疗效及安全性。方法采用艾森卒中风险评分（ESRS）量表筛选住院的急性非心源性缺血性脑卒中复发高危患者100例,随机分为氯吡格雷组和阿司匹林组,每组50例。两组均给予脑卒中常规治疗,氯吡格雷组予氯吡格雷75mg及阿司匹林100mg口服,1周后仅予氯吡格雷75mg,口服。阿司匹林组予阿司匹林200mg,口服,1周后改为100mg,口服。随访3个月和1年,观察两组缺血性脑卒中复发率及药物不良反应发生率。结果随访3个月时,脑卒中复发率：阿司匹林组为6．3％,氯吡格雷组为2．0％,差异无统计学意义（P〉0．05）;药物不良反应发生率：阿司匹林组为14％,氯吡格雷组为2％,差异有统计学意义（P〈0．05）。随访1年时,脑卒中复发率：阿司匹林组为13％,氯吡格雷组为2％,差异有统计学意义（P〈0．05）;药物不良反应发生率：阿司匹林组为38％,氯吡格雷组为6％,差异有统计学意义（P〈0．01）。结论缺血性脑卒中复发高危患者二级预防中强化抗血小板治疗可降低脑卒中复发风险,长期应用获益较高,安全性好。     

个体化抗血小板治疗对缺血性卒中二级预防的效果研究

目的 研究个体化抗血小板治疗在缺血性卒中二级预防的效果。 方法 选择2013年3月-2014年5月于陕西省人民医院就诊的急性缺血性卒中患者207例,随机分为 常规治疗组与个体化治疗组。常规治疗组应用阿司匹林100 mg/d抗血小板治疗。个体化治疗组应用 Essen卒中风险评分量表（Essen Stroke Risk Score,ESRS）将高危组给予氯吡格雷75 mg/d,低危组给 予阿司匹林100 mg/d抗血小板治疗。7 d后进行血栓弹力图（thromboela stogram,TEG）及CYP2C19基因型 检测,结合TEG及CYP2C19基因型结果,决定抗血小板治疗方案。随访1年,比较个体化治疗组和常规 治疗组患者终点事件发生率。 结果 CYP2C19快代谢基因型、中间代谢基因型患者应用氯吡格雷的血小板抑制率明显高于慢代谢 型,结果差异有显著性（P =0.018,P =0.015）。个体化治疗组（112例）和常规治疗组组（95例）终点事 件发生率差异无显著性（P＞0.01）。 结论 CYP2C19快代谢基因型、中间代谢基因型患者应用氯吡格雷的血小板抑制率明显高于慢代谢 型。与阿司匹林常规治疗方案相比,利用CYP2C19基因多态性与TEG检测指导下的个体化抗血小板方 案未显示降低缺血性卒中后终点事件发生率,可能需要更大规模、随访时间更长的研究。     

Dual Antiplatelet Therapy of Clopidogrel and Aspirin in Secondary Prevention of Ischemic Stroke: Evidence and Indications

Nowadays the dual antiplatelet therapy (DAPT) becomes more widely used in patients with ischemic stroke. Nevertheless, controversies exist for indications of DAPT. In view of evidence‐based medicine analysis, patients with high‐risk transient ischemic attack and minor stroke, severe symptomatic intracranial artery stenosis, symptomatic intracranial and extracranial artery stenosis causing artery‐to‐artery embolism, ischemic stroke attributed to aortic arch plaques, high‐risk atrial fibrillation not suitable for oral anticoagulants, intracranial and extracranial stent implantation, and ischemic stroke with acute coronary syndrome may gain great benefit from DAPT of clopidogrel and aspirin. In clinical practice, individualized antiplatelet therapy strategies should be taken by weighing risks of ischemia and hemorrhage.