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1、缺血性卒中抗栓循证治疗复旦大学附属中山医院神经内科汪 昕证据等级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急性缺血性卒中溶栓治疗概述 静脉溶栓 组织纤溶酶原激活物（tPA） NINDS ECASS I 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 Sca
2、le at 90 days rtPA 与安慰剂组无明显差别rt-PA : ECASS IHacke et al., JAMA. 1995;274:1017-1025 随机, 多中心, 双盲, 安慰剂对照 800 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 days rtPA 与安慰剂组无明显差别rt-PA : ECASS IIHacke et al., Lancet. 1998;352:1245-1251 随机, 多中心, 双盲, 安慰剂对照 61
3、3例 干预 rtPA (0.9 mg/kg) vs. placebo 起病3-5h内 主要终点 NIHSS of 1 at 90 days rtPA 与安慰剂组无明显差别rt-PA : ATLANTIS Alteplase Thrombolysis for Acute Noninterventional Rx in Isch StrokeClark et al., JAMA. 1999;282:2019-2026rt-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 类证据链激酶（S
4、K）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 MU 300 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 (ASK)Donnan et al., Lancet 1995;3
5、45:578-9SK1.5 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 类证据动脉溶栓 前循环 大脑中动脉阻塞 后循环 椎基底动脉阻塞 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% 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
6、, 1995;5:182-7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. 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类证据急性缺血性卒中抗凝治疗概述 肝素 LMW heparin LMW 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 interaction longer half-life si
7、mpler to administer lower bleeding risk reduced effect on IIaSummary: trial resultsNdrugresultsCanadian225Hep IVno differenceIST19,435Hep scno differenceTOAST1281heparinoidno difference large art better at 3 mo?HK308LMWH dead/dep at 6 moFISS767LMWHno differenceTAIST1486LMWHno differenceTOPAS404LMWHn
8、o difference among doses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 静脉血栓形成各卒中亚型急性抗凝治疗:小结CCTsubgrpNresults心源性栓塞123618no 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-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类证据急性缺血性卒中阿司匹林治疗International Stroke Str
9、ial (IST)ASA 300 mg/d x 2 wks begun within 48 hrs2 wk endptsASA N=9720No ASA N=9715 Recurrent ischemic2.8%*3.9%All recurrent stroke3.7%4.6%Major extracranial bleed1.1%*0.6%Death9.0%9.4%* p 4mm Level III: benefit34 patients with mobile atheroma Level III: benefitFerrari E et al JACC 1999;33:1317-22主动
10、脉弓粥样硬化 Tunick P et al Am J Cardiol 2002;90:1320-5Level III evidence: benefit of statins主动脉弓粥样硬化: OAC Tunick P et al Am J Cardiol 2002;90:1320-5Level III evidence: no benefit of OAC主动脉弓粥样硬化: APA Tunick P et al Am J Cardiol 2002;90:1320-5Level III evidence: no benefit of APA主动脉弓粥样硬化: 他汀类 Tunick P et a
11、l Am J Cardiol 2002;90:1320-5Level III evidence: benefit of statins 1 stroke prevention Retrospective data show no benefit of OAC for native valve endocarditis, benefit for prosthetic valve endocarditis1-5 2 stroke prevention: No data感染性心内膜炎1Davenport et al Stroke 1990;21:993-92Paschalis et al Eur N
12、eurol 1990;30:87-9 3Yeh 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 ? Pathogenesis: fibrin thrombi deposits on valves assoc with coagulopathy (usually DIC) Reported incidence of embolism varies (14-91%) Rx: Retros
13、pective data suggest benefit of heparin, but not OAC1-3 68% with recurrent emboli when heparin d/cd ICH 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 evidence: no benefit of OAC
14、; benefit of heparin in Trousseau syndrome (mainly with DIC)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 - .64) Bleeding2.8 (1.7 - 4.8) Major bleeding OAC 2.8%/yr vs. ASA 0.9%/y
15、rLevel I Evidence: benefit of OACOptimum 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 at 3.0”Stroke Prevention with the ORal direct Thrombin Inhibitor in patients with non- valvular atrial Fibrillation(SPORTIF
16、) 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。心肌梗死后一级预防: 短期抗凝 Pre-thrombolytic era Heparin decreases stroke incidence 1-3 Heparin decreases mural thrombus 41Med Rese
