缺血性脑卒中抗血小板药物治疗

缺血性脑卒中缺血性脑卒中 抗血小板药物治疗抗血小板药物治疗 天津医科大学第二医院神经内科天津医科大学第二医院神经内科 李李 新新 卒中是致死致残的首位疾病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、健康和生卒中是全球多发性疾病，它威胁生命、健康和生 活质量活质量 卒中有很多预防、治疗和康复卒中的手段卒中有很多预防、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卒中专业人员和非专业群众了解卒中是行动的第 一步一步 世界卒中日宣言世界卒中日宣言 Vladimir Hachinski Vladimir Hachinski 李新李新 解读世界卒中日宣言解读世界卒中日宣言 中华医学杂志中华医学杂志 2010,90(1):70 2010,90(1):70 “One in Six“- “One in Six“- 可能就是你可能就是你 20102010年年 世界卒中日主题世界卒中日主题 one in six people one in six people worldwide will have a worldwide will have a stroke in their lifetime. stroke in their lifetime. Every six seconds, Every six seconds, someone somewhere someone somewhere will die from a stroke.will die from a stroke. Save a life today. Save a life today. Act Now Act Now ！ 20112011年：年： Every Day Is a World Stroke Day: Every Day Is a World Stroke Day: Act Now, Be a Stroke Champion and a Torchbearer Act Now, Be a Stroke Champion and a Torchbearer (1) how to ensure that (1) how to ensure that what we know will what we know will translate intotranslate into what we do in daily what we do in daily practice,practice, （2 2）how to educate how to educate the public on a the public on a healthier lifestyle healthier lifestyle worldwide in spite worldwide in spite of cultural,social, of cultural,social, and religious and religious differencesdifferences 卒中是可防可治的疾病卒中是可防可治的疾病 世界卒中日的总主题世界卒中日的总主题 STROKE: A PREVENTABLE STROKE: A PREVENTABLE AND TREATABLE AND TREATABLE CATASTROPHECATASTROPHE 卒中是可防可治的疾病卒中是可防可治的疾病 预防为主预防为主 （一）（一） 卒中是可以预防的卒中是可以预防的 但是全球的发病率日渐增高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、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，卒中造成世界范围不论年龄、性别、种族和国家，卒中造成5.75.7百万百万/ /年死亡，年死亡， 是全球的第二死亡原因（我国为首位）是全球的第二死亡原因（我国为首位） 4/54/5卒中发生在低或中等收入的国家，防治卒中的支付能力很小卒中发生在低或中等收入的国家，防治卒中的支付能力很小 若针对卒中的现状无所作为，至若针对卒中的现状无所作为，至20152015年预期死于卒中人数将达到年预期死于卒中人数将达到6.76.7 百万百万/ /年年 若现有的防治措施能真正落实和付诸实现，到若现有的防治措施能真正落实和付诸实现，到20182018年能避免年能避免6 6百万人百万人 死于卒中死于卒中 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，特别是预防效的手段，特别是预防 （二）（二） 联合一切力量来联合一切力量来预防预防卒中卒中 - -世界范围首要健康问题之一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、肿瘤以还是造成心脏病、糖尿病、慢性肺疾病、肿瘤以 及阿尔茨海默（及阿尔茨海默（AlzheimerAlzheimer）病的病原性危险因）病的病原性危险因 素素 所以，我们需要联合所有医疗卫生机构和单位，所以，我们需要联合所有医疗卫生机构和单位， 协力努力工作，预防这些病因性危险因素的增长协力努力工作，预防这些病因性危险因素的增长 趋势趋势 （三）（三） 保证将我们所知道的都付诸实际，保证将我们所知道的都付诸实际， 预防是最容易实预防是最容易实 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，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健康的环境，以支持健康的习惯和生活方式 鼓励使用鼓励使用有效的药物预防有效的药物预防高危人群发病（高危人群发病（一级预防）和已患脑血管病）和已患脑血管病 者再发病（者再发病（二级预防二级预防）。但是，在很多发展中国家，这些药难以得到）。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 于效于效/ /价不符的治疗和研究；结果是使得确实有效（效价不符的治疗和研究；结果是使得确实有效（效/ /价合理）药物价合理）药物 和治疗手段的医疗资源被挤掉，不能造福患者和治疗手段的医疗资源被挤掉，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），卒中的症状是无痛的（缺血性），常常是常常是 暂时的（暂时的（TIATIA） 出现下列症状是卒中的征兆应立即急诊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突然不能说话或不能理解他人的语言 单眼视力丧失单眼视力丧失 突然丧失平衡突然丧失平衡 卒中的定义卒中的定义 Definition of StrokeDefinition of Stroke (WHO in 1980)(WHO in 1980) “rapidly developing clinical signs of focal (at times “rapidly developing clinical signs of focal (at times global) disturbance of cerebral function, lasting global) disturbance of cerebral function, lasting more than 24 hours more than 24 hours or or leading to death leading to death with no with no apparent cause other than that of apparent cause other than that of vascular originvascular origin” ” This definition includes signs and symptoms This definition includes signs and symptoms suggestive of suggestive of ischemic strokeischemic stroke hemorrhages hemorrhages (intracerebral or subarachnoid)(intracerebral or subarachnoid) The WHO defines stroke as 不包括TIA 脑血管病脑血管病 = = Stroke Stroke （卒中卒中） WHO WHO 定义定义现代概念现代概念 TIA = TIA/TIA = TIA/小卒中的定义小卒中的定义 （见后）（见后） TIA/TIA/小卒中临床意义相同：小卒中临床意义相同： 皆有高发皆有高发major major 卒中等危险性卒中等危险性 需紧急处理！需紧急处理！ TIA = TIA/TIA = TIA/小卒中的定义小卒中的定义 （见后）（见后） TIA/ TIA/小卒中临床意义相小卒中临床意义相 同：同： 皆有高发皆有高发major major 卒中、卒中、 心梗和其他血管事件心梗和其他血管事件 的危险性的危险性 需紧急处理！需紧急处理！ TIA/TIA/小卒中是小卒中是 预防治疗的最佳时机预防治疗的最佳时机 The The 90-day risk of90-day risk of stroke stroke after a after a TIA has been reported as TIA has been reported as being as high as being as high as 17%,17%, with the with the greatest risk greatest risk apparent apparent in the first weekin the first week. . Stroke Stroke 处理的目的处理的目的 1 1“ “血管血管“ “ 阻塞的再通（溶栓，栓子取出术），侧枝循环阻塞的再通（溶栓，栓子取出术），侧枝循环 2.2. “ “脑脑” ”病变的处理：缺血和再灌注造成脑损害的处理病变的处理：缺血和再灌注造成脑损害的处理 3 3 “ “血管血管” ”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 脑脑 血管血管 病病 TIATIA只对只对3 3 Cerebro vascular diseases Cerebro vascular diseases 脑实质病损脑实质病损 血管病原病变血管病原病变 卒中病种亚型卒中病种亚型 “ “脑缺血脑缺血” ”损害的治疗靶点损害的治疗靶点 及时抢救及时抢救“ “ 缺血半暗带缺血半暗带” ” Ischemic Penumbra Ischemic Penumbra TIATIA的处理的目的的处理的目的 1 1无无“ “血管血管“ “ 阻塞阻塞，无需再通（溶栓，栓子取出术），侧枝，无需再通（溶栓，栓子取出术），侧枝 循环循环 2.2. 无脑损害无脑损害，无需，无需“ “脑脑” ”病变的处理，脑保护的治疗病变的处理，脑保护的治疗 3 3 “ “血管血管” ”病原的处理：造成缺血的心血管病原和病理发病病原的处理：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机制；以及血管危险因素的处理 目的目的 预防预防再发卒中，心肌梗死和其他血管事件的发生再发卒中，心肌梗死和其他血管事件的发生 目的 血小板抑制剂用于血小板抑制剂用于卒中处理卒中处理 缺血性缺血性StrokeStroke指南指南 有关血小板抑制剂部分有关血小板抑制剂部分 血小板抑制剂卒中临床应用血小板抑制剂卒中临床应用 急性缺血性卒中急性缺血性卒中 卒中一级预防卒中一级预防 卒中二级预防卒中二级预防 【介绍最新指南的推荐介绍最新指南的推荐】 临床实践指南临床实践指南- -简称简称“ “指南的目的指南的目的” ” （ clinical practice guidelinesclinical practice guidelines） 改善患者的预后改善患者的预后 综合综合最新最新的临床研究的临床研究 决定是否决定是否具体实践具体实践能到达现代能到达现代 证据证据- -基础的基础的推荐推荐 降低实践中的变数降低实践中的变数 影响有关政策的制定影响有关政策的制定 促进医疗有效资源的利用促进医疗有效资源的利用 识别证据基础（循证医学）的识别证据基础（循证医学）的 缺陷缺陷 用做发展用做发展“ “工作指标工作指标” ” 和和“ “适当应适当应 用标准用标准” ”的基础的基础 Improve patient outcomes Improve patient outcomes Synthesis of latest clinical research Synthesis of latest clinical research Determine whether practice follows Determine whether practice follows the current evidence-based the current evidence-based recommendations recommendations Reduce practice variation Reduce practice variation Influence policy Influence policy Promote efficient resource usage Promote efficient resource usage Identify gaps in the evidence base Identify gaps in the evidence base Serve as a basis for development Serve as a basis for development of of Performance Measures Performance Measures and and Appropriate Use Criteria Appropriate Use Criteria 【 to critically and systematically to critically and systematically create, review, and categorize the create, review, and categorize the appropriate use of certain appropriate use of certain cardiovascular diagnostic testscardiovascular 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 mg d(I级推荐，A级证据)。急性期后可改为预防剂量(50 150 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) 急性缺血性卒中急性缺血性卒中 aspirin aspirin 的使用的使用 AHA/ASAAHA/ASA指南指南 Guidelines for the Early Management of Guidelines for the Early Management of Adults With Ischemic Stroke:Adults With Ischemic Stroke: Stroke 2007; 38: 1655-171Stroke 2007; 38: 1655-171 Class I RecommendationClass I Recommendation 一级推荐一级推荐 The oral administration of aspirin (initial dose is 325 The oral administration of aspirin (initial dose is 325 mg) within 24 to 48 hours after stroke onset is mg) within 24 to 48 hours after stroke onset is recommendedrecommended for treatment of most patients (Class for treatment of most patients (Class I, Level ofI, Level of Evidence A).Evidence A). a small but statistically significant decline in riska small but statistically significant decline in risk of mortality and morbidity when aspirin is started of mortality and morbidity when aspirin is started within 48within 48 hours after onset of stroke. It appears that hours after onset of stroke. It appears that the the primary effectsprimary effects of the aspirinof the aspirin are due to are due to reduction of early recurrent strokereduction of early recurrent stroke rather than rather than limitation of the neurological consequences of thelimitation of the neurological consequences of the stroke stroke Class III RecommendationClass III Recommendation 三级推荐三级推荐 （不能（不能-not-not） 1. Aspirin should 1. Aspirin should notnot be considered a be considered a substitute for othersubstitute for other acute interventions for acute interventions for treatment of stroke, includingtreatment of stroke, including the the intravenous administration of rtPA (Class III, intravenous administration of rtPA (Class III, LevelLevel of Evidence B). of Evidence B). 续续 2. The administration of aspirin as an 2. The administration of aspirin as an adjunctive therapyadjunctive therapy within 24 hours of within 24 hours of thrombolytic therapy is thrombolytic therapy is notnot recommendedrecommended (Class III, Level of (Class III, Level of Evidence A). Evidence A). 续续 3. The administration of clopidogrel alone or in 3. The administration of clopidogrel alone or in combinationcombination with aspirin is with aspirin is notnot recommended for the recommended for the treatmenttreatment of acute ischemic stroke (Class III, Level of of acute ischemic stroke (Class III, Level of Evidence C).Evidence C) . The panel supports research testing theThe panel supports research testing the usefulness of emergency administration of usefulness of emergency administration of clopidogrelclopidogrel in the treatment of patients with acute in the treatment of patients with acute strokestroke 续续 4. Outside the setting of clinical trials, the 4. Outside the setting of clinical trials, the intravenousintravenous administration of antiplatelet administration of antiplatelet agents that inhibit theagents that inhibit the glycoprotein IIb/IIIa glycoprotein IIb/IIIa receptor is receptor is notnot recommended recommended (Class III, Level (Class III, Level of Evidence of Evidence B). B). 一级预防一级预防 AHA/ASAAHA/ASA 20112011年年 指南指南 Guidelines for the Guidelines for the PrimaryPrimary Prevention of StrokePrevention of Stroke A Guideline for Health care Professionals A Guideline for Health care Professionals From the American Heart Association/ From the American Heart Association/ American Stroke AssociationAmerican Stroke Association The American Academy of Neurology The American Academy of Neurology affirms the value of this guideline as an affirms the value of this guideline as an educational tool for neurologistseducational tool for neurologists Stroke. Stroke. 20112011;42:517584;42:517584 摘要摘要 Background and PurposeBackground and PurposeThis This guideline provides an guideline provides an overview of the evidence on established and emerging risk overview of the evidence on established and emerging risk factors factors for stroke to provide evidence-based recommendations for stroke to provide evidence-based recommendations for the reduction of risk of a first stroke.for the reduction of risk of a first stroke. MethodsMethodsWriting group members were nominated by the Writing group members were nominated by the committee chair on the basis of their previous work in relevant committee chair on the basis of their previous work in relevant topic areas and were approved topic areas and were approved 。The writing group used The writing group used systematic literature reviews (covering the time since the last systematic literature reviews (covering the time since the last review was published in review was published in 2006 up to April 20092006 up to April 2009), reference to ), reference to previously published guidelines, personal files, and expert previously published guidelines, personal files, and expert opinion to summarize existing evidence, indicate gaps in opinion to summarize existing evidence, indicate gaps in current knowledge, and when appropriate, formulate current knowledge, and when appropriate, formulate recommendations using standard AHA criteria (recommendations using standard AHA criteria (Tables 1 and 2Tables 1 and 2). ). 摘要摘要 ResultsResultsSchemes for assessing a Schemes for assessing a persons risk of a first stroke persons risk of a first stroke were were evaluated. evaluated. Risk factors or risk markers Risk factors or risk markers for a firstfor a first stroke were stroke were classifieclassified d according to according to potential for modification potential for modification ( (nonmodifiable, modifiable, or nonmodifiable, modifiable, or potentially modifiablepotentially modifiable) and ) and strength of evidence strength of evidence (well documented or less well (well documented or less well documented). documented). 【 Non modifiable risk factors Non modifiable risk factors】 include age, sex, low birth weight, include age, sex, low birth weight, race/ethnicity, and genetic predisposition.race/ethnicity, and genetic predisposition. 【 Well-documented and modifiable risk factors Well-documented and modifiable risk factors】 include hypertension,include hypertension, exposure to cigarette smoke, diabetes, atrial fibrillation and certain other exposure to cigarette smoke, diabetes, atrial fibrillation and certain other cardiac conditions, dyslipidemia, carotid arterycardiac conditions, dyslipidemia, carotid artery stenosis, sickle cell disease, stenosis, sickle cell disease, postmenopausal hormone therapy, poor diet, physical inactivity, and obesity postmenopausal hormone therapy, poor diet, physical inactivity, and obesity and body fat distribution.and body fat distribution. 【 Less well-documented or potentially modifiable risk factors Less well-documented or potentially modifiable risk factors】 include the include the metabolic syndrome, excessivemetabolic syndrome, excessive alcohol consumption, drug abuse, use of oral alcohol consumption, drug abuse, use of oral contraceptives, sleep-disordered breathing, migraine, hyperhomocysteinemia,contraceptives, sleep-disordered breathing, migraine, hyperhomocysteinemia, elevated lipoprotein(a), hypercoagulability, inflammation, and infection. elevated lipoprotein(a), hypercoagulability, inflammation, and infection. Data on the use of aspirin for primaryData on the use of aspirin for primary stroke prevention are reviewedstroke prevention are reviewed. . 续续 ConclusionConclusionExtensive evidence identifies a variety of specific Extensive evidence identifies a variety of specific factors that increase the risk of a first stroke and thatfactors that increase the risk of a first stroke and that provide provide strategies for reducing that risk. (Stroke. 2011;42:517-584.)strategies for reducing that risk. (Stroke. 2011;42:517-584.) Data on the use of aspirin Data on the use of aspirin for primaryfor primary stroke stroke preventionprevention 其他内容见原文其他内容见原文 Stroke. 2011;42:517-584Stroke. 2011;42:517-584 Aspirin for Primary Stroke Aspirin for Primary Stroke PreventionPrevention 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 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 IIa; Level of Evidence B). 续（续（notnot） 3. Aspirin is 3. Aspirin is notnot useful for preventing a first stroke in useful for preventing a first stroke in persons at low risk ( persons at low risk (Class III; Level of Evidence A).Class III; Level of Evidence A). 4. Aspirin is 4. Aspirin is notnot useful for preventing a first stroke in useful for preventing a first stroke in persons with diabetes or diabetes plus asymptomatic persons with diabetes or diabetes plus asymptomatic peripheral artery disease (defined as an ankle brachial peripheral artery disease (defined as an ankle brachial pressure index 75 75岁岁 2 2 高血压高血压 1 1 糖尿病糖尿病 1 1 心肌梗塞心肌梗塞 1 1 其他心血管事件其他心血管事件 1 1 周围血管病周围血管病 1 1 吸烟吸烟 1 1 TIA/MIS TIA/MIS附加卒中附加卒中/TIA 1/TIA 1 评分评分 3 3分说明分说明TIA/MISTIA/MIS患者的卒中再发率为患者的卒中再发率为 4%/4%/年年 评价评价TIA/MISTIA/MIS认知功能认知功能障碍的危险性障碍的危险性 MoCAMoCA量表量表 MoCAMoCA MoMontreal ntreal C Cognitive ognitive A Assessmentssessment 提供提供： 英文、中文、广东话英文、中文、广东话 3 3 个版本的：个版本的： MoCA MoCA的量表的量表 使用说明使用说明 MoCAMoCA对对TIA/MIS TIA/MIS 的的MCIMCI的敏感性超过的敏感性超过MMSEMMSE MoCAMoCA中文版中文版 附注：附注： （1 1）教育水平：受教育教育水平：受教育 1212年年( (初初 中中) )者，总分加者，总分加1 1分。分。 （2 2）提示回忆不记分。提示回忆只）提示回忆不记分。提示回忆只 用于临床目的，为检查者分用于临床目的，为检查者分 析患者的记忆障碍类型时提析患者的记忆障碍类型时提 供附加信息。对于提取障碍导供附加信息。对于提取障碍导 致的记忆缺陷，暗示可提高回致的记忆缺陷，暗示可提高回 忆成绩；如果是编码障碍，则忆成绩；如果是编码障碍，则 提示无助于提高回忆成绩。提示无助于提高回忆成绩。 散发性小动脉病散发性小动脉病 的病理发生机制的病理发生机制 不详不详 抗血小板制剂效果不详抗血小板制剂效果不详 A AS SCOCO 病理发生机制病理发生机制 A A 大动脉的粥样硬化（微栓）大动脉的粥样硬化（微栓） S S 散发性脑小血管病散发性脑小血管病 （？病理？）（？病理？） C C 心源性栓子心源性栓子 （动脉粥样硬化和其他（动脉粥样硬化和其他 ） O O 其他（遗传、