缺血性脑卒中抗血小板药物治疗

1、缺血性脑卒中抗血小板药物治疗,天津医科大学第二医院神经内科 李 新,卒中是致死致残的首位疾病,卒中是全球多发性疾病，它威胁生命、健康和生活质量 卒中有很多预防、治疗和康复卒中的手段 卒中专业人员和非专业群众了解卒中是行动的第一步 世界卒中日宣言 vladimir hachinski 李新 解读世界卒中日宣言 中华医学杂志 2010,90(1):70,“one in six“- 可能就是你2010年 世界卒中日主题,one in six people worldwide will have a stroke in their lifetime. every six seconds, someon

2、e somewhere will die from a stroke. save a life today. act now ！,2011年： every day is a world stroke day: act now, be a stroke champion and a torchbearer,(1) how to ensure that what we know will translate into what we do in daily practice,（2）how to educate the public on a healthier lifestyle worldwid

3、e in spite of cultural,social, and religious differences,卒中是可防可治的疾病 世界卒中日的总主题,stroke: a preventable and treatable catastrophe,卒中是可防可治的疾病,预防为主,（一） 卒中是可以预防的但是全球的发病率日渐增高,人群的高龄化、不健康饮食和体力活动少等促进高血压、高胆固醇、肥胖、糖尿病、卒中、心脏病和血管性认知功能障碍的发生和发展 世界范围不论年龄、性别、种族和国家，卒中造成5.7百万/年死亡，是全球的第二死亡原因（我国为首位） 4/5卒中发生在低或中等收入的国家，防治卒中的

4、支付能力很小 若针对卒中的现状无所作为，至2015年预期死于卒中人数将达到6.7百万/年 若现有的防治措施能真正落实和付诸实现，到2018年能避免6百万人死于卒中 在预防和处理卒中，以及对因卒中残废患者的康复治疗有很多行之有效的手段，特别是预防,（二） 联合一切力量来预防卒中-世界范围首要健康问题之一,但是对这种最常见的威胁人类健康和生命的疾病的研究，却和其他重要慢性疾病孤立分割开来 最常见的危险因素有：吸烟、体力活动缺乏、不健康的饮食、（我国还有酣酒）等除造成卒中外还是造成心脏病、糖尿病、慢性肺疾病、肿瘤以及阿尔茨海默（alzheimer）病的病原性危险因素 所以，我们需要联合所有医疗卫生机

5、构和单位，协力努力工作，预防这些病因性危险因素的增长趋势,（三） 保证将我们所知道的都付诸实际， 预防是最容易实 现见效的，也正是我们的知识的用武之地。但是预防确被忽略，所以我们应该,鼓励健康的环境，以支持健康的习惯和生活方式 鼓励使用有效的药物预防高危人群发病（一级预防）和已患脑血管病者再发病（二级预防）。但是，在很多发展中国家，这些药难以得到和支付困难；而在发达国家又难以合理地最佳使用 不鼓励使用未经规范临床试验证实的、价格昂贵的和误导（如药理和所治疾病不符）的药物和治疗手段，理由是消耗过多的医疗资源，用于效/价不符的治疗和研究；结果是使得确实有效（效/价合理）药物和治疗手段的医疗资源被挤

6、掉，不能造福患者 教育各级健康和医务人员：通过各种方式如普及教育、基础课程、网上资料、远程咨询等机会学习和提高临床实践能力,提高对卒中病因和症状的认识,卒中的症状是无痛的（缺血性），常常是暂时的（tia） 出现下列症状是卒中的征兆应立即急诊 突然的面部、上肢或下肢无力或麻木 突然不能说话或不能理解他人的语言 单眼视力丧失 突然丧失平衡,卒中的定义,definition of stroke (who in 1980),“rapidly developing clinical signs of focal (at times global) disturbance of cerebral func

7、tion, lasting more than 24 hours or leading to death with no apparent cause other than that of vascular origin” this definition includes signs and symptoms suggestive of ischemic stroke hemorrhages (intracerebral or subarachnoid),the who defines stroke as,不包括tia,脑血管病 = stroke （卒中）,who 定义,现代概念,tia =

8、tia/小卒中的定义（见后）,tia/小卒中临床意义相同： 皆有高发major 卒中等危险性 需紧急处理！,tia = tia/小卒中的定义（见后）,tia/小卒中临床意义相同： 皆有高发major 卒中、心梗和其他血管事件的危险性 需紧急处理！,tia/小卒中是 预防治疗的最佳时机 the 90-day risk of stroke after a tia has been reported as being as high as 17%, with the greatest risk apparent in the first week.,stroke 处理的目的,1“血管“ 阻塞的再通（

9、溶栓，栓子取出术），侧枝循环 2. “脑”病变的处理：缺血和再灌注造成脑损害的处理 3 “血管”病原的处理：造成缺血的心血管病原和病理发病机制的处理 脑 血管 病 tia只对3 cerebro vascular diseases 脑实质病损 血管病原病变 卒中病种亚型,“脑缺血”损害的治疗靶点及时抢救“ 缺血半暗带” ischemic penumbra,tia的处理的目的,1无“血管“ 阻塞，无需再通（溶栓，栓子取出术），侧枝循环 2. 无脑损害，无需“脑”病变的处理，脑保护的治疗 3 “血管”病原的处理：造成缺血的心血管病原和病理发病机制；以及血管危险因素的处理 目的 预防再发卒中，心肌梗死

10、和其他血管事件的发生,目的,血小板抑制剂用于卒中处理,缺血性stroke指南 有关血小板抑制剂部分,血小板抑制剂卒中临床应用,急性缺血性卒中 卒中一级预防 卒中二级预防 【介绍最新指南的推荐】,临床实践指南-简称“指南的目的” （ clinical practice guidelines）,改善患者的预后 综合最新的临床研究 决定是否具体实践能到达现代证据-基础的推荐 降低实践中的变数 影响有关政策的制定 促进医疗有效资源的利用 识别证据基础（循证医学）的缺陷 用做发展“工作指标” 和“适当应用标准”的基础,improve patient outcomes synthesis of lates

11、t clinical research determine whether practice follows the current evidence-based recommendations reduce practice variation influence policy promote efficient resource usage identify gaps in the evidence base serve as a basis for development of performance measures and appropriate use criteria 【 to

12、critically and systematically create, review, and categorize the appropriate use of certain cardiovascular diagnostic tests】,中国急性缺血性脑卒中诊治指南2010,抗血小板： 大样本试验(中国急性脑卒中试验和国际脑卒中试验)研究了脑卒中后48 h内口服阿司匹林的疗效，结果显示，阿司匹林能显著降低随访期末的病死或残疾率，减少复发，仅轻度增加症状性颅内出血的风险 一个预试验提示轻型脑梗死或tia患者早期联用氯吡格雷与阿司匹林是安全的，可能减少血管事件但差异无统计学意义 目前尚

13、无评价其他抗血小板药物在脑卒中急性期临床疗效的大样本rct报道,中国急性缺血性脑卒中诊治指南2010,抗血小板： 推荐意见： (1)对于不符合溶栓适应证且无禁忌证的缺血性脑卒中患者应在发病后尽早给予口服阿司匹林150300 mgd(i级推荐，a级证据)。急性期后可改为预防剂量(50150 mgd)，详见二级预防指南 (2)溶栓治疗者，阿司匹林等抗血小板药物应在溶栓24 h后开始使用(i级推荐，b级证据) (3)对不能耐受阿司匹林者，可考虑选用氯吡格雷等抗血小板治疗(级推荐，c级证据),急性缺血性卒中 aspirin 的使用,aha/asa指南 guidelines for the early

14、management of adults with ischemic stroke: stroke 2007; 38: 1655-171,class i recommendation一级推荐,the oral administration of aspirin (initial dose is 325 mg) within 24 to 48 hours after stroke onset is recommended for treatment of most patients (class i, level of evidence a). a small but statistically

15、 significant decline in risk of mortality and morbidity when aspirin is started within 48 hours after onset of stroke. it appears that the primary effects of the aspirin are due to reduction of early recurrent stroke rather than limitation of the neurological consequences of the stroke,class iii rec

16、ommendation三级推荐 （不能-not）,1. aspirin should not be considered a substitute for other acute interventions for treatment of stroke, including the intravenous administration of rtpa (class iii, level of evidence b).,续,2. the administration of aspirin as an adjunctive therapy within 24 hours of thromboly

17、tic therapy is not recommended (class iii, level of evidence a).,续,3. the administration of clopidogrel alone or in combination with aspirin is not recommended for the treatment of acute ischemic stroke (class iii, level of evidence c). the panel supports research testing the usefulness of emergency

18、 administration of clopidogrel in the treatment of patients with acute stroke,续,4. outside the setting of clinical trials, the intravenous administration of antiplatelet agents that inhibit the glycoprotein iib/iiia receptor is not recommended (class iii, level of evidence b).,一级预防,aha/asa 2011年 指南,

19、guidelines for the primary prevention of stroke,a guideline for health care professionals from the american heart association/ american stroke association the american academy of neurology affirms the value of this guideline as an educational tool for neurologists stroke. 2011;42:517584,摘要,backgroun

20、d and purposethis guideline provides an overview of the evidence on established and emerging risk factors for stroke to provide evidence-based recommendations for the reduction of risk of a first stroke. methodswriting group members were nominated by the committee chair on the basis of their previou

21、s work in relevant topic areas and were approved 。the writing group used systematic literature reviews (covering the time since the last review was published in 2006 up to april 2009), reference to previously published guidelines, personal files, and expert opinion to summarize existing evidence, in

22、dicate gaps in current knowledge, and when appropriate, formulate recommendations using standard aha criteria (tables 1 and 2).,摘要,resultsschemes for assessing a persons risk of a first stroke were evaluated. risk factors or risk markers for a first stroke were classified according to potential for

23、modification (nonmodifiable, modifiable, or potentially modifiable) and strength of evidence (well documented or less well documented). 【 non modifiable risk factors】 include age, sex, low birth weight, race/ethnicity, and genetic predisposition. 【 well-documented and modifiable risk factors】 includ

24、e hypertension, exposure to cigarette smoke, diabetes, atrial fibrillation and certain other cardiac conditions, dyslipidemia, carotid artery stenosis, sickle cell disease, postmenopausal hormone therapy, poor diet, physical inactivity, and obesity and body fat distribution. 【 less well-documented o

25、r potentially modifiable risk factors】 include the metabolic syndrome, excessive alcohol consumption, drug abuse, use of oral contraceptives, sleep-disordered breathing, migraine, hyperhomocysteinemia, elevated lipoprotein(a), hypercoagulability, inflammation, and infection. data on the use of aspir

26、in for primary stroke prevention are reviewed.,续,conclusionextensive evidence identifies a variety of specific factors that increase the risk of a first stroke and that provide strategies for reducing that risk. (stroke. 2011;42:517-584.),data on the use of aspirin for primary stroke prevention,其他内容

27、见原文 stroke. 2011;42:517-584,aspirin for primary stroke prevention,recommendation 1. the use of aspirin for cardiovascular (including but not specific to stroke) prophylaxis is recommended for persons whose risk is sufficiently high for the benefits to outweigh the risks associated with treatment (a

28、10-year risk of cardiovascular events of 6% to 10%) (class i; level of evidence a). 2. aspirin (81 mg daily or 100 mg every other day) can be useful for prevention of a first stroke among women whose risk is sufficiently high for the benefits to outweigh the risks associated with treatment (class ii

29、a; level of evidence b).,续（not）,3. aspirin is not useful for preventing a first stroke in persons at low risk (class iii; level of evidence a). 4. aspirin is not useful for preventing a first stroke in persons with diabetes or diabetes plus asymptomatic peripheral artery disease (defined as an ankle

30、 brachial pressure index 0.99) in the absence of other established cvd (class iii; level of evidence b). 5. the use of aspirin for other specific situations (eg, atrial fibrillation, carotid artery stenosis) is discussed in the relevant sections of this statement.【省略】,二级预防,中国缺血性脑卒中和短暂性脑缺血发作二级预防指南201

31、0,心源性栓塞的抗栓治疗 心房颤动 推荐意见： (1)对于心房颤动(包括阵发性)的缺血性脑卒中和tia患者，推荐使用适当剂量的华法林口服抗凝治疗，以预防再发的血栓栓塞事件。华法林的目标剂量是维持inr在2030(i级推荐，a级证据) (2)对于不能接受抗凝治疗的患者，推荐使用抗血小板治疗(i级推荐，a级证据)。氯吡格雷联合阿司匹林优于单用阿司匹林(i级推荐，a级证据),中国缺血性脑卒中和短暂性脑缺血发作二级预防指南2010,心源性栓塞的抗栓治疗 急性心肌梗死和左心室血栓 推荐意见： (1)急性心肌梗死并发缺血性脑卒中和tia的患者应使用阿司匹林，剂量推荐为75325 mgd(i级推荐，a级证据

32、) (2)对于发现有左心室血栓的急性心肌梗死并发缺血性脑卒中或tia脑卒中的患者，推荐使用华法林抗凝治疗至少3个月，最长为1年，控制inr水平在203o(级推荐，b级证据),中国缺血性脑卒中和短暂性脑缺血发作二级预防指南2010,心源性栓塞的抗栓治疗 瓣膜性心脏病 推荐意见： (1)对于有风湿性二尖瓣病变的缺血性脑卒中和tia患者，无论是否合并心房颤动，推荐使用华法林抗凝治疗，目标为控制inr在2030(级推荐，c级证据)。不建议在抗凝的基础上加用抗血小板药物以避免增加出血性并发症的风险(级推荐，c级证据) (2)对于已规范使用抗凝剂的风湿性二尖瓣病变的缺血性脑卒中和tia患者，仍出现复发性栓

33、塞事件的，建议加用抗血小板治疗(级推荐，c级证据) (3)对于有缺血性脑卒中和tia病史的二尖瓣脱垂患者，可采用抗血小板治疗(级推荐，c级证据) (4)对于有缺血性脑卒中和tia病史伴有二尖瓣关闭不全、心房颤动和左心房血栓者建议使用华法林治疗(级推荐，c级证据) (5)对于有缺血性脑卒中和tia史的二尖瓣环钙化患者，可考虑抗血小板治疗或华法林治疗(iv级推荐，d级证据) (6)对于有主动脉瓣病变的缺血性脑卒中和tia患者，推荐进行抗血小板治疗(级推荐，c级证据) (7)对于有人工机械瓣膜的缺血性脑卒中和tia患者，采用华法林抗凝治疗，目标inr控制在2535(级推荐，b级证据) (8)对于有人

34、工生物瓣膜或风险较低的机械瓣膜的缺血性脑卒中和tia患者，抗凝治疗的目标inr控制在2030(ii级推荐，b级证据) (9)对于已使用抗凝药物inr达到目标值的患者，如仍出现缺血性脑卒中或tia发作，可加用抗血小板药(级推荐，c级证据),中国缺血性脑卒中和短暂性脑缺血发作二级预防指南2010,心源性栓塞的抗栓治疗 心肌病与心力衰竭 推荐意见： (1)对于有扩张性心肌病的缺血性脑卒中和tia患者，可考虑使用华法林抗凝治疗(控制inr在2030)或抗血小板治疗预防脑卒中复发(级推荐，c级证据) (2)对于伴有心力衰竭的缺血性脑卒中和tia患者，可使用抗血小板治疗(级推荐，c级证据),中国缺血性脑卒

35、中和短暂性脑缺血发作二级预防指南2010,非心源性缺血性脑卒中和t1a的抗栓治疗 非心源性指由于动脉粥样硬化、小动脉闭塞、其他少见病因或病因不明所导致的缺血性脑卒中和tia 抗血小板药物在非心源性缺血性脑卒中和tia二级预防中的应用 抗血小板治疗能显著降低既往有脑卒中或tia患者再次严重血管事件的发生率，包括非致命性心肌梗死、非致命性脑卒中和血管源性死亡,中国缺血性脑卒中和短暂性脑缺血发作二级预防指南2010,非心源性缺血性脑卒中和t1a的抗栓治疗 抗血小板药物在非心源性缺血性脑卒中和tia二级预防中的应用 1阿司匹林：阿司匹林50一1300 mgd能一定程度上降低脑卒中的再发，但大剂量与小剂

36、量阿司匹林在预防血管性事件方面效果相似，并且大剂量阿司匹林使胃肠道出血的风险增高 2氯吡格雷：与阿司匹林相比，氯吡格雷在预防血管性事件发生方面优于阿司匹林。对高危患者(曾发生脑卒中、外周动脉疾病、症状性冠状动脉疾病或糖尿病)，其效果可能更加明显,中国缺血性脑卒中和短暂性脑缺血发作二级预防指南2010,非心源性缺血性脑卒中和t1a的抗栓治疗 抗血小板药物在非心源性缺血性脑卒中和tia二级预防中的应用 3双嘧达莫：与安慰剂组相比，双嘧达莫不管何种剂型均不能显著减少血管性死亡事件的发生率，但可以减少血管性事件的发生率，尤其对于脑血管病组。没有证据表明单用双嘧达莫比阿司匹林更有效,中国缺血性脑卒中和短

37、暂性脑缺血发作二级预防指南2010,非心源性缺血性脑卒中和t1a的抗栓治疗 抗血小板药物在非心源性缺血性脑卒中和tia二级预防中的应用 4双嘧达莫+阿司匹林： 欧洲脑卒中预防试验-2发现，与单独应用阿司匹林相比，联合应用阿司匹林(38300 mgd)和双嘧达莫(缓释片200 mg，2次d)能够降低血管性死亡，脑卒中或心肌梗死的危险 profess研究显示，阿司匹林+缓释双嘧达莫复方制剂与氯吡格雷预防脑卒中及血管性事件疗效相当；但阿司匹林与缓释双嘧达莫复方制剂的主要出血事件(包括颅内出血)风险显著高于氯吡格雷。头痛是阿司匹林+缓释双嘧达莫复方制剂常见的不良事件，可降低患者依从性,47,preve

38、ntion regimen for effectively avoiding second strokes,中国缺血性脑卒中和短暂性脑缺血发作二级预防指南2010,非心源性缺血性脑卒中和t1a的抗栓治疗 抗血小板药物在非心源性缺血性脑卒中和tia二级预防中的应用 5氯吡格雷+阿司匹林： 近期有tia或缺血性脑卒中的高危患者用阿司匹林与氯吡格雷加阿司匹林的对照研究(match)表明，与单用氯吡格雷相比，氯吡格雷与阿司匹林联合治疗在减少缺血性脑卒中、心肌梗死、血管性死亡或因缺血性事件再次入院组成的联合终点或者任何次要转归指标方面没有显著益处 联合治疗组发生严重出血的风险显著高于单用氯吡格雷组 12

39、个月内曾发生急性冠状动脉事件或行冠状动脉支架植入术的患者，联合应用氯吡格雷和阿司匹林能够降低新发血管事件的风险,中国缺血性脑卒中和短暂性脑缺血发作二级预防指南2010,非心源性缺血性脑卒中和t1a的抗栓治疗 抗血小板药物在非心源性缺血性脑卒中和tia二级预防中的应用 6新型抗血小板药物： 三氟柳与西洛他唑组、阿司匹林与三氟柳组严重血管事件发生率差异无统计学意义，三氟柳组出血事件发生率显著低于阿司匹林组 西洛他唑与阿司匹林在缺血性脑卒中二级预防中的应用研究(casisp)发现，在中国的缺血性脑卒中患者中进行二级预防可能有效和安全，从而可能代替阿司匹林在二级预防中的应用，但是这一结论尚需更大规模的

40、3期临床试验进一步验证,2010中国缺血性卒中/tia二级预防指南推荐意见,ia,对于非心源性栓塞性缺血性卒中或tia患者，除少数情况需要抗凝治疗，大多数情况均建议给予抗血小板药物预防缺血性卒中/tia复发 抗血小板药物的选择以单药治疗为主，氯吡格雷(75 mg/d)、阿司匹林(50325 mg/d)都可以做为首选药物 有证据表明氯吡格雷优于阿司匹林，尤其对于高危患者获益更显著 不推荐常规应用双重抗血小板药物。但对于有急性冠状动脉疾病(例如不稳定型心绞痛，无q波心肌梗死)或近期有支架成形术的患者，推荐联合应用氯吡格雷+阿司匹林,ia,ia,非心源性缺血性卒中/tia的抗栓治疗,中华医学会神经病

41、学分会脑血管病学组指南写作组，2010中国缺血性卒中/短暂性脑缺血发作二级预防指南，中华神经科杂志 2010；43（2）： 154160,2010中国缺血性脑卒中/tia二级预防指南推荐意见,iiic,无抗凝禁忌症的动脉夹层患者发生缺血性脑卒中或tia后，首选静脉肝素，维持活化部分凝血活酶时间50-70s，或低分子肝素治疗；随后改为口服华法林抗凝治疗（inr2.0-3.0），通常使用3-6个月，随访6个月，如果仍然存在动脉夹层，需要长期抗血小板药物治疗 存在抗凝禁忌症的动脉夹层患者，需要抗血小板治疗3-6个月，随访6个月，如果仍然存在动脉夹层，需要长期抗血小板药物治疗 药物治疗失败的动脉夹层患

42、者，可以考虑血管内治疗或者外科手术治疗,其他特殊情况下脑卒中患者的治疗：动脉夹层,中华医学会神经病学分会脑血管病学组指南写作组，2010中国缺血性卒中/短暂性脑缺血发作二级预防指南，中华神经科杂志 2010；43（2）：154160,iiic,iiic,2010中国缺血性脑卒中/tia二级预防指南推荐意见,iiic,55岁以下不明原因的缺血性脑卒中和tia患者，应进行卵圆孔未闭筛查 不明原因的缺血性脑卒中和tia合并卵圆孔未闭患者，使用抗血小板治疗，如果存在深静脉血栓形成，房间隔瘤或者存在抗凝治疗其他指征如心房颤动、高凝状态，建议华法林治疗（inr2.0-3.0） 不明原因的缺血性脑卒中和ti

43、a合并卵圆孔未闭患者,经过充分治疗，仍然发生缺血性卒中者，可以选择血管内卵圆孔未闭封堵术,其他特殊情况下脑卒中患者的治疗：卵圆孔未闭,中华医学会神经病学分会脑血管病学组指南写作组，2010中国缺血性卒中/短暂性脑缺血发作二级预防指南，中华神经科杂志 2010；43（2）：154160,iiic,iiic,二级预防,aha/asa 2011年指南,guidelines for the prevention of stroke in patients with stroke or transient ischemic attack,a guideline for healthcare profes

44、sionals from the american heart association/american stroke association the american academy of neurology affirms the value of this guideline as an educational tool for neurologists. the american association of neurological surgeons and congress of neurological surgeons have reviewed this document a

45、nd affirm its educational content stroke. 2011;42:227-276,摘要,abstractthe aim of this updated statement is to provide comprehensive and timely evidence-based recommendations on the prevention of ischemic stroke among survivors of ischemic stroke or tia. evidence-based recommendations are included for

46、 the control of risk factors, interventional approaches for atherosclerotic disease, antithrombotic treatments for cardioembolism, and the use of antiplatelet agents for noncardioembolic stroke. further recommendations are provided for the prevention of recurrent stroke in a variety of other specifi

47、c circumstances, including arterial dissections; patent foramen ovale; hyperhomocysteinemia; hypercoagulable states; sickle cell disease; cerebral venous sinus thrombosis; stroke among women, particularly with regard to pregnancy and the use of postmenopausal hormones; the use of anticoagulation aft

48、er cerebral hemorrhage; and special approaches to the implementation of guidelines and their use in high-risk populations. (stroke. 2011;42:227-276.),2011二级预防指南的新观念 -1,1. stroke和tia的二级预防无区别,因为 many of the preventive approaches are applicable to both tia and ischemic stroke share pathophysiologic mec

49、hanisms,2011二级预防指南的新观念-2,tia 诊断应用时间-基础的 24 小时的定义,因为： the majority of studies described in this guideline used the older definition,iv. antithrombotic therapyfor noncardioembolic stroke or tia (specifically, atherosclerotic, lacunar, orcryptogenic infarcts)（a） antiplatelet agents,其他内容见原文 (stroke. 201

50、1;42:227-276.),recommendation涉及的药物,aspirin ticlopidine clopidogrel dipyridamole and aspirin combination of clopidogrel and aspirin newer agents,recommendation-1,1. for patients with noncardioembolic ischemic stroke or tia, the use of antiplatelet agents rather than oral anticoagulation is recommende

51、d to reduce the risk of recurrent stroke and other cardiovascular events (class i; level of evidence a).,recommendation-2,2. aspirin (50 mg/d to 325 mg/d) monotherapy (class i; level of evidence a), the combination of aspirin 25 mg and extended-release dipyridamole 200 mg twice daily (class i; level

52、 of evidence b), and clopidogrel 75 mg monotherapy (class iia; level of evidence b) are all acceptable options for initial therapy. the selection of an antiplatelet agent should be individualized on the basis of patient risk factor profiles, cost, tolerance, and other clinical characteristics.,recom

53、mendation-3,3. the addition of aspirin to clopidogrel increases the risk of hemorrhage and is not recommended for routine secondary prevention after ischemic stroke or tia (class iii; level of evidence a).,recommendation-4,4. for patients allergic to aspirin, clopidogrel is reasonable (class iia; le

54、vel of evidence c).,recommendation-5,5. for patients who have an ischemic stroke while taking aspirin, there is no evidence that increasing the dose of aspirin provides additional benefit. although alternative antiplatelet agents are often considered, no single agent or combination has been studied

55、in patients who have had an event while receiving aspirin (class iib; level of evidence c) (table 9).,制定指南的“指南”(方法和政策),methodologies and policies for guideline writing. accf/aha task force on practice guidelines january 2010,1. overview of methodology . 4 1.1. importance of accf/aha guidelines . 4 1

56、.2. purpose and scope of the manual . 5 1.3. staff support . 8 2. tools and methods for developing guidelines . 9 2.1. selecting topic and chair/writing committee . 9 2.2. determining the guideline scope and clinical objectives .15 2.2.1. determining the guidelines scope . . 15 2.2.2. identifying th

57、e clinical objectives . . 18 2.2.3. development of the guideline outline . . 18 2.2.4. determining writing assignments . . 20 3. defining and conducting appropriate and comprehensive literature searches . 22 3.1. finding the evidence . . . 22 3.1.1. literature search methodology . . 22 3.1.2. docume

58、ntation of literature search . . 23 3.1.3. balancing scientific rigor with feasibility . . 24 3.2. sorting the evidence . . 32 3.2.1. reviewing the evidence . . 32 3.3. synthesizing and interpreting the evidence . . 33 3.3.1. synthesizing the evidence . . 33 3.4. expert interpretation of the evidenc

59、e . . 35 4. writing recommendations . . 36 4.1. overview of recommendations . . 36 4.1.1. patient-centered care . 39 4.2. assigning classification of recommendations and level of evidence . 39 4.2.1. classification of recommendations and level of evidence . 41 4.2.2. applying the classifications and

60、 levels. . . 42 4.2.3. performance measures . . 43 4.3. creating visual descriptions of recommendations and evidence . 44 4.3.1. communicating the key points . . 44 4.3.2. creating tables . . 45 4.3.3. creating figures . . 48 4.3.4. additional important points on tables and figures . . 50,5. writing