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1、缺血性卒中抗栓缺血性卒中抗栓循证循证治疗治疗别逞任酣赡阑过盂乌去故旦对筷柑据珊菏堵写抛双难骸间狱送促听鲸聪影缺血性卒中的抗栓治疗缺血性卒中的抗栓治疗证据等级I类证据随机对照试验， 假阳性和假阴性错误低II类证据随机对照试验， 假阳性和假阴性错误高III类证据非随机对列研究IV类证据回顾性非随机对列研究，V类证据经验性研究Cook et al., Chest, 1992; 102: 305S-311S炯坎驾让轨茅绵夜乳铰榴徊肄步氧诬胞材仔蝶瞻冉欢邮遂士闽闲壮竭墙牧缺血性卒中的抗栓治疗缺血性卒中的抗栓治疗急性缺血性卒中溶栓治疗蝶枣伦烁止椎槐话泽棒述烷看汁闽戎近抿渠顾眩安劣刊攀邑据苟巩竟日韦缺血性卒
2、中的抗栓治疗缺血性卒中的抗栓治疗概述静脉溶栓组织纤溶酶原激活物（tPA） NINDSECASS I & II, ATLANTIS链激酶 MAST-I, MAST-E, ASK动脉溶栓前循环: 大脑中动脉 (PROACT II)后循环: 基底动脉 横氦千埂碳陌矣斡岁猫艘舔那澄岿挟孰瓶饶肩送救黄棱第态买隋峙陌骤汝缺血性卒中的抗栓治疗缺血性卒中的抗栓治疗与安慰剂相比，3h内IV rtPA (0.9 mg/kg) 能改善90天时的预后出血发生率为 6.4% ，安慰剂为 0.6% ，但死亡率无差异所有亚组预后均优于安慰剂组益处可持续1年rt-PA :NINDS 媚忙稚跃骆慷都片啄疥羔遂答镜耶硒易征粤蹄似
3、叔锰凄星蹲李齐酸汁斥驴缺血性卒中的抗栓治疗缺血性卒中的抗栓治疗随机, 多中心, 双盲, 安慰剂对照620例; 排除CT早期梗塞灶 (预后不良)干预rtPA (1.1 mg/kg) vs. placebo起病6h内 主要终点Barthel Index and modified Rankin Scale at 90 daysrtPA 与安慰剂组无明显差别rt-PA : ECASS IHacke et al., JAMA. 1995;274:1017-1025姜汕室酋抹淆厂槐雏豺倍酱荔诡奉仓优笼况牺夺遥岿阮斗缕寐桐紊半婚提缺血性卒中的抗栓治疗缺血性卒中的抗栓治疗随机, 多中心, 双盲, 安慰剂对照8
4、00 例;排除CT早期明显梗塞灶 干预rtPA (0.9 mg/kg) vs. placebo起病6h内 主要终点modified Rankin Scale Score of 1 at 90 daysrtPA 与安慰剂组无明显差别rt-PA : ECASS IIHacke et al., Lancet. 1998;352:1245-1251痔矩捷篙受稠柄架亨克撞膜隘沟控升绽危待讲费噪顽捂究移饥介挚瞥俐酣缺血性卒中的抗栓治疗缺血性卒中的抗栓治疗随机, 多中心, 双盲, 安慰剂对照613例干预rtPA (0.9 mg/kg) vs. placebo起病3-5h内 主要终点NIHSS of 1 at
5、 90 daysrtPA 与安慰剂组无明显差别rt-PA : ATLANTISAlteplase Thrombolysis for Acute Noninterventional Rx in Isch StrokeClark et al., JAMA. 1999;282:2019-2026撰逾芳偶降禾汇脊课薛投索坐碴喇纬侯汹咬浓兄波误酶熬绪冻借聋檀告哟缺血性卒中的抗栓治疗缺血性卒中的抗栓治疗rt-PA:小结与安慰剂相比，3h内IV rtPA (0.9 mg/kg) 能改善90天时的预后. I 类证据目前证据显示，超过3h 予IV tPA 无效. I 类证据租眼甄打砾泞头鼠皿捏郴涯钙孔绍仁纠飘毁
6、救船疯长忌拈悄窗这铀烙居闺缺血性卒中的抗栓治疗缺血性卒中的抗栓治疗链激酶（SK）研究药物剂量治疗窗结果Multicenter Acute Stroke Trial-Europe (MAST-E)NEJM 1996;335:145-50SK1.5 MU6hSK组出血和死亡率高提前终止试验Multicenter Acute Stroke Trial-Italy (MAST-I)Lancet 1995;346:1509-14SK aspirin1.5 MU300 mg/d6hSK组，尤其是SK + aspirin组出血和死亡率高提前终止试验Australian Streptokinase Trial
7、 (ASK)Donnan et al., Lancet 1995;345:578-9SK1.5 MU4h提前终止; 治疗窗4h无明显益处，结果不良与安慰剂相比，6h内予IV SK 1.5 MU 预后不良 (出血和死亡率高). I 类证据力竿遭靠砧喊顿冬念烯今宝盲扶纠姚笋赦省浇晕酌毡秋凶似株邑爱醉奈仲缺血性卒中的抗栓治疗缺血性卒中的抗栓治疗动脉溶栓前循环大脑中动脉阻塞后循环椎基底动脉阻塞按斥山媳抚嗣揪刑荷戍具骋闪跟喳唐直氨姻否禄非逝退仍篷撮悸凑布愁憾缺血性卒中的抗栓治疗缺血性卒中的抗栓治疗与安慰剂相比, 6h内予IA ProUK 经造影证实MCA M1 或M2 段阻塞的患者有效. I 类证据15
8、% 绝对有效 (number needed to treat = 7)增加颅内出血，死亡率无差异PROACT II:小结猿镁炙滦猛否愚淳吕酬商初抓艘巴仙拿面撕勇党韵娶堂班啦勘质醋减削谩缺血性卒中的抗栓治疗缺血性卒中的抗栓治疗急性椎基底动脉阻塞数项病例报道 (IV、V 类证据)非随机化无对照组 Brandt et al., Cerebrovasc Dis, 1995;5:182-7随叫赌缺络仕刨稽骄睦操崩昆瑟正拼眺序舜篙捕洼难孕涣铺蜡诈塔船脱雇缺血性卒中的抗栓治疗缺血性卒中的抗栓治疗小结3h内静脉用 tPA 能降低90天时的残障功能. I类证据静脉用链激酶 (1.5 MU) 增加出血和死亡率.
9、I类证据6h内动脉用尿激酶前体(Pro-UK,未被FDA通过)能降低90天时的残障功能. I类证据有证据支持在急性椎基底动脉阻塞中应用动脉溶栓. IV、V类证据端哇先划打伙移恤淡匈莲显奏夺敞釉案搂位舔睬驹营讣返鬃誊抱食扫黑保缺血性卒中的抗栓治疗缺血性卒中的抗栓治疗急性缺血性卒中抗凝治疗噬跃松趋芍曹诱金许扦薄膏秃缮升押糊拧骚卢寅蛛琴洁醒领揍宗付魄席晦缺血性卒中的抗栓治疗缺血性卒中的抗栓治疗概述肝素LMW heparinLMW heparinoid- 作用于抗凝血酶 III (抑制凝血因子 IIa, IXa, and Xa) 1 effect on Xa reduced plt interacti
10、on longer half-life simpler to administer lower bleeding risk reduced effect on IIa伴牲退虑掀妮韦寝好挛破直哆捅版长艘存咏获刮坊滞燕库墟逼勤刑效碳捆缺血性卒中的抗栓治疗缺血性卒中的抗栓治疗Summary: trial resultsNdrugresultsCanadian225Hep IVno differenceIST19,435Hep scno differenceTOAST1281heparinoidno differencelarge art better at 3 mo?HK308LMWH dead/d
11、ep at 6 moFISS767LMWHno differenceTAIST1486LMWHno differenceTOPAS404LMWHno difference among doses嘉斩振吸迟躬膏羔效辖章敖障匀玫碟铂姿嫩陀诊嗜断凯弓恨莫碟幂皇樟抿缺血性卒中的抗栓治疗缺血性卒中的抗栓治疗各卒中亚型急性抗凝治疗 房颤 和心源性栓塞大动脉粥样硬化椎基底动脉阻塞 TIA进展性卒中动脉夹层静脉血栓形成禄癌随恫礁咯套凳酬读窒咙祝绑郊亲诫煮戮裂爪脊踏刽鸟疆矾渣靴尺突遥缺血性卒中的抗栓治疗缺血性卒中的抗栓治疗各卒中亚型急性抗凝治疗:小结CCTsubgrpNresults心源性栓塞123618no
12、diff大动脉硬化0413,2851+(?)/3-后循环032318no diffTIA1055no diff进展性卒中20204no diff夹层00286no diff静脉血栓20791+/1-舆唆评怂循桥婶荔访嫂辕响溉配驾傲胺涩荐刺寥详嗅菩动榴蕴叔郁水消党缺血性卒中的抗栓治疗缺血性卒中的抗栓治疗小结急性期抗凝减少深静脉血栓和肺栓塞发生，不增加颅内出血几率.I类证据 呻析裙株竭觉侗蝴汐就炙啦誉比戈镶芳洒焕悍诱醒稀线檄盂云吵空避乖普缺血性卒中的抗栓治疗缺血性卒中的抗栓治疗急性缺血性卒中阿司匹林治疗急性缺血性卒中阿司匹林治疗碗决崩哥教珐鼻朝整色扭挥罪掀摩姐示搽股赏坚卵捧琼登蔑挪粹念辕旗购缺血性
13、卒中的抗栓治疗缺血性卒中的抗栓治疗International Stroke Strial (IST)ASA 300 mg/d x 2 wks begun within 48 hrs2 wk endptsASAN=9720No ASAN=9715Recurrent ischemic2.8%*3.9%All recurrent stroke3.7%4.6%Major extracranial bleed1.1%*0.6%Death9.0%9.4%* p.01炊科夯苹喊晌尽紫遥漂赴劣酋谷果饰回首集后钱晴斜倔辕婚例柞叙辛碑步缺血性卒中的抗栓治疗缺血性卒中的抗栓治疗Chinese Acute Strok
14、e Trial (CAST)Lancet 1997;349:1641ASA 160 mg/d x4 wks begun within 48 hrs4 wk endptsASAN=10335PlaceboN=10320Recurrent ischemic1.6%*2.1%All recurrent stroke3.2%3.4%Major extracran bleed0.8%*0.6%Death3.3%*3.9%* p.05茂戈狡搞梧痞凄倘怕抹唆臣卿纤仅咽臣哼重判罩板励楷灯嗅牲融馋汾设掘缺血性卒中的抗栓治疗缺血性卒中的抗栓治疗小结小结基于 IST 和 CAST, 阿司匹林在急性缺血性卒中后2-4
15、周内，每1000例患者中有10人可减少死亡和复发。循只力龙小但勇疫睫靳朝鞋瘦铅励颖樊蛹蜘帅镇臆研弯毖狐辽梧斤汝屡鹏缺血性卒中的抗栓治疗缺血性卒中的抗栓治疗非心源性卒中二级预防：非心源性卒中二级预防：抗栓治疗抗栓治疗低伶浇韵集旭崎专畸憨窍吠该磺南韵脸咖埋嘛谬拿痉靛扬屹暖塑畸琵靶组缺血性卒中的抗栓治疗缺血性卒中的抗栓治疗概述抗血小板药Antiplatelet.阿司匹林Aspirin抵克立得（噻氯匹啶）Ticlid (Ticlopidine)波力维（氯吡格雷）Plavix (Clopidogrel)艾诺思Aggrenox (aspirin + extended-release dipyridamol
16、e)Warfarin for non-cardioembolic arterial stroke: including large vessel disease.抗磷脂抗体综合征（ASP）.颈椎动脉夹层.咕烂盔热纳琴猪贷拐青冉旨逆蜗嘉旋般处谚仅杆唱譬饰抑退战幅粳肄董尝缺血性卒中的抗栓治疗缺血性卒中的抗栓治疗Aspirin融呛摔滴灌卤格颓臣社兔测谋题俞桐鲸铭呐项凉腹眩拖刻乞牧悍契窝缴窃缺血性卒中的抗栓治疗缺血性卒中的抗栓治疗高剂量阿司匹林随机对照试验#StudyASA dose# of ptsAgef/u Prim. Endpoint% of RR1AITIA 1977Medical group
17、1300mgA 88; P 9060.237mTIA, CI, RI, death20 only with TIA. *P (15.7)2AITIA 1977 surgical group650mgA 65; P 6060.3?TIA, CI, RI, deathSame as medical*P (15.7)3CCSG 1978ASA+SP1300mgA 144; P 139?26mTIA, S, death-6 to 31%*P (7.6)4Reuther 19781500mgA 29; P 295924mTIA, SNS*P (8.3)5AICLA 1983ASA+DP990mgA 19
18、8; P 20463.536mFatal; nonfatal CI no TIA included41*P(7.5)6Danish CS 19831000mgA 101; P 1025925mS or Death-77*P (9.6)7Swedish CS 19871500mgA 253; P 2526824mS or Death0*P(10.9)* Risk of vascular events (death, stroke, MI) in the control group悦鞋倦葬渺嘉惦盐链忌大恰蟹口苫谩枢酵岗蒂企锯标抽被铂蛋沥响棘拷驳缺血性卒中的抗栓治疗缺血性卒中的抗栓治疗低剂量阿司匹林
19、随机对照试验#Study ASA dose in mg.#of ptsAgeF/uPrim. Endpoint% in RR1Danish Low 1988 (post CEA)50-100A150P15158.925TIA, S, MI, vascular death11% (NS)*P(7.3)2UK TIA 19911200300Placebo81580681459.848Major S, MI, Vasc. Death 15% vs P; NS between doses*P(5.7)3SALT 199175A676P68466.932S or death16%*P(10.6)4ESP
20、S 250A1649P164966.724S, death or both18%*P(15.8)* Vascular events (death, MI, stroke) in placebo. * stroke in placebo冀型聊伙炽叶聂郑帝屏改有菇似弧腹携垮舟监胺比淮捧鸦珠弯傍辆巩梭脓缺血性卒中的抗栓治疗缺血性卒中的抗栓治疗Antiplatelet Trialists100,000 pts from 145 trials.All antiplatelet agents were included.Clumped all vascular events together.Overal
21、l odds reduction for vascular events was 25%.For pts with minor stroke or TIA (18 trials) antiplatelet agents led to odds reduction of 22% for vascular events and 23% for nonfatal stroke.Did not answer questions about aspirin dose.Used odds ratio instead of relative risk.Used all antiplatelet agents
22、.泌缆梅惨剪禁教袱坞脾笔莫堤嫁勘赚厅脏媳镭甘吗茎赛吵爵佳宝辰福涨惮缺血性卒中的抗栓治疗缺血性卒中的抗栓治疗Is there a consensus. The FDA reviewed trials of aspirin vs placebo (including ESPS-2, SALT, and UK-TIA trials) to reduce the risk of stroke and death in patients with prior TIA or stroke.“The positive findings at lower dosages (eg, 50, 75, and 30
23、0 mg daily), along with the higher incidence of side effects expected at the higher dosage (eg, 1,300 mg daily), are sufficient reason to lower the dosage of aspirin for subjects with TIA and ischemic stroke.”For “ischemic stroke and TIA: 50 to 325 mg aspirin once a day. Continue therapy indefinitel
24、y.”FDA. Federal Register. 1998;63:56802.源毫旁关奎县总桐依瞥些胁镇俏峙薯祭瞻瞎猎臻睦褪橙片囤淫检咖类骤叁缺血性卒中的抗栓治疗缺血性卒中的抗栓治疗Ticlopidine 键惠椭毁浴工俏滦席责弗置碍襄诣浅堆扮妒恕颜甜嘶辊弱宇验虾蚌蓉险萎缺血性卒中的抗栓治疗缺血性卒中的抗栓治疗TASS Study: Efficacy* 3-year study endpoints, N = 3,069.EndpointStrokeStroke, MI, orvascular deathRRR21%9%(P = 0.024)Hass et al. N Engl J Med. 1
25、989;321:501. Easton. In Hass and Easton (eds). Ticlopidine, Platelets and Vascular Disease. New York: Springer-Verlag; 1993:141.* Ticlopidine (250 mg bid) vs ASA (650 mg bid).(NS)力缨裸搅瞒稗浆舒则碟诣灸顽透蝎腹兄垒刊刘朴诀维蒸贵索领哼绦戒知帕缺血性卒中的抗栓治疗缺血性卒中的抗栓治疗Ticlopidine (%)Aspirin (%)DiarrheaRashNauseaGastritis, ulcer, GI blee
26、dingSevere neutropenia (ANC 450/mm3)Cerebral hemorrhage20.4*11.9*11.1 2.10.9*0.69.85.210.2 6.0*0.00.7*P 0.05TASS Study: Side EffectsAdapted from Hass et al. N Engl J Med. 1989;321:501.惕验踏剧炼坷可融叙谤粱癣肩阵袖仗阿羹话反砒么励汉愉垣池匀诊满惩浙缺血性卒中的抗栓治疗缺血性卒中的抗栓治疗Clopidogril圾矫杠捷孰老羡让绵转许救措彩朔处祖酝弱哺抗录啡删躬氯骂酝砌喝契杖缺血性卒中的抗栓治疗缺血性卒中的抗栓治疗C
27、APRIE StudyEfficacy of Clopidogrel vs. Aspirin (n = 19,185)Primary Outcome: MI, Ischemic Stroke, or Vascular DeathMonths of Follow-UpMonths of Follow-UpCumulativeCumulative Event Rate (%)Event Rate (%)0 04 48 812121616ClopidogrelClopidogrelAspirinAspirin0 03 36 69 91212 1515 1818 2121 2424 2727 3030
28、 3333 3636AspirinAspirin5.83%5.83%5.32%5.32%ClopidogrelClopidogrelEvent Rate per YearEvent Rate per Year*P *P = 0.043= 0.043CAPRIE Steering Committee. Lancet 1996;348:1329-1339.CAPRIE Steering Committee. Lancet 1996;348:1329-1339.ARR= 0.51NNT= 1/0.005= 196寺蘑坍巫如淘鲸贯剁纲吾潜邮葬邵宋迹阮在醛锦绣绰次守侯肆漱慰岛龚政缺血性卒中的抗栓治疗缺血
29、性卒中的抗栓治疗Clopidogrel (%)ASA (%)GI complaintsAny bleeding disorderRashDiarrheaGI bleedingIntracranial hemorrhage1.901.200.90*0.420.520.212.41*1.370.410.270.93*0.33*P 0.05CAPRIE Steering Committee. CAPRIE Steering Committee. LancetLancet. 1996;348:1329-1339. 1996;348:1329-1339.Side Effects causing disc
30、ontinuation of drugCAPRIE Study捕估氯握淡候玉惭既挨抉宣沮必吕腋枕鼠搓案砚试畴傣痕枕馋纱篮竹景稠缺血性卒中的抗栓治疗缺血性卒中的抗栓治疗Management of Atherothrombosis with Clopidogrel in High-risk patients（MATCH） 氯吡格雷（75mg）+阿司匹林（75mg）与单用氯吡格雷（75mg）的疗效进行比较 ，结果是失败的两组的主要终点指标，即缺血性卒中、心肌梗死和血管源性死亡发生率与急性缺血事件（心绞痛、周围动脉症状恶化或TIA）无统计学差异 联合治疗同时增加了严重出血的概率 唬渊覆坑黎高饭又铆金郡
31、筏肥埋携愚锐害婴台盖兰塌卑颗径迅婪阳隅陀谈缺血性卒中的抗栓治疗缺血性卒中的抗栓治疗The Second European Stroke Prevention Study:ESPS-2Tested efficacy of ASA/ER-DP for secondary stroke preventionAddressed clinical questionsDoes low-dose ASA prevent stroke?Does ER-DP prevent stroke?Is ASA/ER-DP superior to ASA alone? To ER-DP alone?Is ASA/ER-D
32、P well tolerated?The ESPS-2 Group. J Neurol Sci. 1997;151:S3. Diener et al. J Neurol Sci. 1996;143:1.釉部钻颂粮三婶蕉兰律陷新沥羹碟结睡喇鱼氛缩胸墒蛆胚绞不练豌御肉纪缺血性卒中的抗栓治疗缺血性卒中的抗栓治疗ESPS-2 Results: Stroke Rates at 24 MonthsPlaceboASAER-DP ASA/ER-DP048121615.2%12.5%12.8%9.5%Incidence (%)ARR= 5.7 over PlaceboNNT= 1/0.057= 17.5御晃贸
33、姐戴王讯威粱镣撒惹瘫啦蟹筑抢酸惮铝杰蒋旁垦拄目猴引剪谓袭域缺血性卒中的抗栓治疗缺血性卒中的抗栓治疗ESPS-2 : Side Effect Profile Placebo ASA ASA+EDGI Event*28.1% 30.4%32.8%Headache*32.3%33.1%38.1%Bleeding * 4.5%8.2%8.7%(any site)Lightheadedness 30.9%29.1%29.5%*=P 4mmLevel III: benefit34 patients with mobile atheromaLevel III: benefitFerrari E et al
34、JACC 1999;33:1317-22散扦云由氖关郡翟赋拷揩睁嫩赠疙磐计杭盛滓齐咬棒高普梗规庇尺偶铭糕缺血性卒中的抗栓治疗缺血性卒中的抗栓治疗主动脉弓粥样硬化Tunick P et al Am J Cardiol 2002;90:1320-5Level III evidence: benefit of statins蚤糊务哟割拓跪盂婪据切棺炬浮冕糙漂陡鹊糟刷星笆淮西臃亲辞培桑沈鸵缺血性卒中的抗栓治疗缺血性卒中的抗栓治疗主动脉弓粥样硬化: OACTunick P et al Am J Cardiol 2002;90:1320-5Level III evidence: no benefit of
35、 OAC苇暴誊撞竭种孙趋隆拐蓄饼辩贴球察换审莱沫脏憎日题炽禽杀贴搐产驭韧缺血性卒中的抗栓治疗缺血性卒中的抗栓治疗主动脉弓粥样硬化: APATunick P et al Am J Cardiol 2002;90:1320-5Level III evidence: no benefit of APA劝喝枫母锚森垣课保洋磺冬沏文翟蛤采忌唤呐缚队咆剥手泽稿反隘椅窄殆缺血性卒中的抗栓治疗缺血性卒中的抗栓治疗主动脉弓粥样硬化: 他汀类Tunick P et al Am J Cardiol 2002;90:1320-5Level III evidence: benefit of statins诣蚕喧告乃墅很
36、屈碎套闪世躬连粒搂复书囊封静捐驳彰囚习酪家村广抹幌缺血性卒中的抗栓治疗缺血性卒中的抗栓治疗1 stroke prevention Retrospective data show no benefit of OAC for native valve endocarditis, benefit for prosthetic valve endocarditis1-52 stroke prevention: No data感染性心内膜炎1Davenport et al Stroke 1990;21:993-92Paschalis et al Eur Neurol 1990;30:87-9 3Yeh
37、et al Circulation 1967;35:I77-814Delahaye et al Eur Heart J 1990;11:1074-85Wilson et al Circulation 1978;57:1004-7Level V evidence百庭朱卤洽杆遵海鼎旁辜梳迎赎晃坊玉翁迈篱邻瞧捡糯麓潘喷轰咋讹颠营缺血性卒中的抗栓治疗缺血性卒中的抗栓治疗? Pathogenesis: fibrin thrombi deposits on valves assoc with coagulopathy (usually DIC)Reported incidence of embolism
38、varies (14-91%)Rx: Retrospective data suggest benefit of heparin, but not OAC1-368% with recurrent emboli when heparin d/cdICH risk lower than in infective endocarditis1Rogers et al Am J Med 1987;83:746-562Lopez et al Am Heart J 1987;113:773-843Sack et al Medicine 1977;56:1-37非细菌性血栓性心内膜炎Level V evid
39、ence: no benefit of OAC;benefit of heparin in Trousseau syndrome (mainly with DIC)样片淀乒书窜坦浚峭姬斟铜趣娜椭砷掏泼簧厕驶翔绍搬谁哼筋东飞墨划弄缺血性卒中的抗栓治疗缺血性卒中的抗栓治疗European Atrial Fibrillation Trial：EAFT (Lancet 1993;342:1255-1262)Oral anticoagulants (225) vs. Aspirin (230) HR (95%CI)1 Endpoint0.60 (.41 - .87)All stroke0.38 (.23
40、 - .64)Bleeding2.8 (1.7 - 4.8) Major bleeding OAC 2.8%/yr vs. ASA 0.9%/yr Level I Evidence: benefit of OAC道苑挞童类擂正狞憋唾箭留妓厄赠狙吴山惕总咯惯佬反沼蔡厉席寓愿洋雇缺血性卒中的抗栓治疗缺血性卒中的抗栓治疗Optimum INR for prevention of 2 stroke associated with atrial fibrillation(EAFT NEJM 1995;333:5-10)“The target value for the INR should be set
41、 at 3.0”减臃境汉学傅丸庙蝴彰音达酝库彦醒殃窖腮彦混瓤讨喇奴罪阵巧夕剪姓莲缺血性卒中的抗栓治疗缺血性卒中的抗栓治疗Stroke Prevention with the ORal direct Thrombin Inhibitor in patients with non-valvular atrial Fibrillation(SPORTIF) SPORTIF III是一项开放试验 , SPORTIF V期是随机双盲多中心试验 ；比较了口服直接凝血酶抑制剂西美加群（ximelagatran）与华法林（INR23）对心房颤动罹患卒中的影响 ；两组预防缺血性卒中的疗效无统计学差异，华法林组并
42、发出血的概率较高，西美加群组肝酶升高发生率为6%，比华法林组（0.8%）高很多，这也是尚未获得美国FDA批准的原因。锈圃羞授藕漳泳巴邓吹凯观侦恰旭侯禾桐忙浮陇阳殆喻翔警棍灌满取策厢缺血性卒中的抗栓治疗缺血性卒中的抗栓治疗心肌梗死后一级预防: 短期抗凝Pre-thrombolytic eraHeparin decreases stroke incidence 1-3Heparin decreases mural thrombus 41Med Research Council BMJ 1969;1:335-422Drapkin & Merskey JAMA 1972;222:541-83VA Co
43、op Study JAMA 1973;225:724-94Vaitkus & Barnathau JACC 1993;22:100-9衡菌利咐闯厂宏戳哺跺矽汽拂驮鳃藻啃玻吠妥暂捂弦丁拯颜库揪辞蜗罐贪缺血性卒中的抗栓治疗缺血性卒中的抗栓治疗心肌梗死后一级预防: 短期抗凝Post-thrombolytic erabaseline rates of death, reinfarction, stroke, & PE markedly lower with thrombolytics & ASAaddition of heparin/LMWH may decrease mural thrombus f
44、ormation, but increases risk of major bleeding without further reducing stroke risk1Collins et al BMJ 1996;313:652-9 2Collins et al NEJM 1997;336:847-603FRAMI Kontny et al JACC 1997;30:962-94SCATI Lancet 1989;2:182-65Gissi-2 Vecchio et al Circulation 1991;84:512-9宦碎酞蹲淖蝎奉掇五容绰洁佃躁潭竟召律雅火泄表痈导公拖波摈雹鳃纺壹缺血性卒
45、中的抗栓治疗缺血性卒中的抗栓治疗心肌梗死后一级预防: 长期抗凝Relative to control, coumarins in moderate or high dose (INR 2-4.8)Significantly decrease stroke incidenceSignificantly increase incidence of major bleedingAnand & Yusuf JAMA 1999;282:2058-67刚纷炬忻凌序佳硝融刨民葛朴理瘟伤跨强舱韵荒布罕妊稿阶押厦嚼邦健签缺血性卒中的抗栓治疗缺血性卒中的抗栓治疗Modified from Anand & Yusu
46、f JAMA 1999;282:2058-67But no benefit relative to ASAIncidence of strokeand significant increase in major bleeding茨弥蕴薛衰棘霄悄蒸扦哀全侄揍弄痘锡肤踏氰雍雨粥剖洼邮勒菠蚊肉锚呢缺血性卒中的抗栓治疗缺血性卒中的抗栓治疗 RR (95%CI)Anticoagulation * .19 (.13 - .27)Aspirin # .44 (.29 - .65) Level III evidence: benefit of AC ASA for 1 prevention左心室功能不全 :卒
47、中危险因子多变量分析(Loh E et al NEJM 1997;336:251-257)* similar risk at all levels of EF40%# similar risk at all levels of EF35%婴巾蹄缩火电凤祷视遵镐业援道刘弘渭峪借蹋筑抵揽吟缚冰蹿堪董宰橇虑缺血性卒中的抗栓治疗缺血性卒中的抗栓治疗Rate (Events/ 100 Pt-Yr)Anticoagulation 0 (0/40)No Anticoagulation 0.35 (1/288) Low Risk for Primary Occurrence慢性室壁瘤系统栓塞(Lapeyre
48、AC et al JACC 1985;6:534-538)屏罪盏拄宣盏平县坏椽铱谁枣纬噎鳞逆拽近住警疮税邱骄幻鼓聘蜀撞妈贬缺血性卒中的抗栓治疗缺血性卒中的抗栓治疗Patent Foramen Ovale in Cryptogenic Stroke Study (PICSS)(Homma S et al Circulation 2002;105:2625-31)Design: Prospective, randomized, double- blind, multi-center clinical trial Eligibility: Enrolled in WARSSAgree to have
49、 additional TEETreatment: Warfarin (target INR 1.4-2.8, mean 2.1) vs. aspirin 325 mg1 endpoint : Recurrent ischemic stroke or death within 2 years601 patients42% with cryptogenic stroke as qualifying event34% with PFO木孙煎航躬外敢骆饿以穴慨风劳伴期词擅络炮昌淡神碑糠痹韵焉照烧茧继缺血性卒中的抗栓治疗缺血性卒中的抗栓治疗PICSSLevel II Evidence: No diff
50、erence from aspirinoverall or in any subgroupNo increased event rate in PFO + ASA vs. PFO onlyNo increased rate with larger PFO size偏氰萤浩靖民指美坦茶汀疼堑流逮还诉且夯航州忿褒冕簿姚逃驮利哆事幻缺血性卒中的抗栓治疗缺血性卒中的抗栓治疗Rheumatic MV dz: Level III - Benefit over no OACAortic arch atheroma: Level III - Benefit over APA in 1 study; No be
51、nefit of OAC or APA in another (but benefit of statins)Infective endocarditis: Native valve: Level V - No benefitProsthetic valve: Level V - benefitNBTE: Level V - No benefit (? benefit of heparin)Atrial fibrillation: Level I - Benefit over ASA INR 2.9 (2.5-4.0) PFO: Level II - No benefit over ASA (
52、INR 1.4 2.8)MVP: Level V Not completely effectiveAtrial fibrillation: Level I - Benefit over ASA INR 2.9 (2.5-4.0) PFO: Level II - No benefit over ASA (INR 1.4 2.8)MVP: Level V Not completely effectiveNo dataAortic valve diseaseProsthetic heart valvesMILV dysfunction口服抗凝剂（OAC）二级预防:小结侄痘庶踩伴熄啸融顽异捣女栅唇促邵
53、绢涕谐皑股柄娃吐皆怎孟逛耍杰诣黄缺血性卒中的抗栓治疗缺血性卒中的抗栓治疗Mechanical prosthetic valve: Level I - Benefit of OAC + low dose ASA over OAC aloneBioprosthetic valve: Level V - Benefit over no OAC in 1st 6 weeks after valve replacementMI: Level I - No benefit over ASALVEF 40%: Level III - Benefit ? INR over ASALV aneurysm: lo
54、w risk for 1 occurrence口服抗凝剂（OAC）一级预防:小结幢听金性完沏坟炕昏种随凋叁酬遗刮递阎砧跋文躲找末搔僵襄湍瘪柯微肆缺血性卒中的抗栓治疗缺血性卒中的抗栓治疗心源性卒中二级预防（研究中）NVAF:SPORTIF V (Stroke Prevention by Oral Thrombin Inhibition)Fixed dose ximelagatran (thrombin inhibitor) vs. warfarin (INR 2-3)LV dysfunctionWARCEF (Warfarin vs. Aspirin in Reduced Cardiac EF)
55、Warfarin (INR 2.5-3) vs. ASA 325mg in EF 30%WATCH (Warfarin & Antiplatelet Therapy in Chronic Heart Failure)Warfarin (INR 2.5-3) vs. ASA 162mg vs. Clopidogrel 75mg in EF 35%Aortic Atheroma:ARCH (Aortic Arch Related Cerebral Hazard)warfarin (INR 2-3) vs. ASA + clopidogrel in mobile or 4mm-thick ather
56、omaPFO:RESPECT (Evaluation of Recurrent Stroke Comparing PFO Closure to Established Current Standard Care Treatment Trial)Percutaneous PFO closure vs. antithrombotic Rx (ASA, clopidogrel, Aggrenox, ASA + clopidogrel, warfarin in cryptogenic stroke with PFO)浓圃晤疽臀薪迫炸漫奠伯似运脓哭湾祟恶贮巾隧骄陨雄占予音磺堪山患旦缺血性卒中的抗栓治疗缺
57、血性卒中的抗栓治疗结语1抗血栓治疗仅能作为卒中预防策略组成部分之一 ；没有任何药物能完全消除卒中的复发风险，多项大规模试验结果为正确、合理地选择抗血栓治疗提供了证据 ；蔼慈区砖韩瘟宦摸脏抚锚抢甫梢脸针喊尧刑津魏袁鄂开论称落扶年秆惶搔缺血性卒中的抗栓治疗缺血性卒中的抗栓治疗结语23h内IV rt-PA(0.9mg/kg)疗效得到公认；3h-6h内IA ProUK证实有效；急性期阿司匹林疗效得到公认；急性期抗凝仅能降低DVT和PE发生率，但对动脉血栓疗效无差异符超猛短搅级竿房室差秤接蛀膜侯平蕊粘泻三萝搏利踏若验款州仍狄脂感缺血性卒中的抗栓治疗缺血性卒中的抗栓治疗结语3若无禁忌，心源性栓塞通常宜选择抗凝治疗，西美加群是一种有前景的华法林替代物； 目前无证据支持抗凝治疗用于PFO、抗磷脂抗体综合征、颅内动脉粥样硬化或腔隙性梗塞患者，而推荐使用阿司匹林； 阿司匹林联合华法林治疗不能增强预防作用，反而会带来更大的出血风险； 阿司匹林和氯吡格雷预防卒中复发的效果相近，阿司匹林联用氯吡格雷并不优于单用氯吡格雷，且出血风险更高； 在抗血小板药联合治疗试验中，只有ESPS2试验能证实阿司匹林联用ER-DIP有协同作用，期待PRoFESS试验能得出同样结论。牺让劈钠渊咎路怠固撩诅噪蛹歉氮翱琳饺玖能舅揖孪纺喇盒损狞踌梅抗红缺血性卒中的抗栓治疗缺血性卒中的抗栓治疗
