缺血性卒中抗栓循证治疗培训课件.ppt

Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,缺血性卒中抗栓循证治疗,*,缺血性卒中抗栓循证治疗,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,2,缺血性卒中抗栓循证治疗,急性缺血性卒中溶栓治疗,3,缺血性卒中抗栓循证治疗,概述,静脉溶栓,组织纤溶酶原激活物（,tPA,）,NINDS,ECASS 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,4,缺血性卒中抗栓循证治疗,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,5,缺血性卒中抗栓循证治疗,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 days,rtPA,与安慰剂组无明显差别,rt-PA:,ECASS I,Hacke et al.,JAMA.1995;274:1017-1025,6,缺血性卒中抗栓循证治疗,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 II,Hacke et al.,Lancet.1998;352:1245-1251,7,缺血性卒中抗栓循证治疗,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 90 days,rtPA,与安慰剂组无明显差别,rt-PA:ATLANTIS,Alteplase Thrombolysis for Acute Noninterventional Rx in Isch Stroke,Clark et al.,JAMA.1999;282:2019-2026,8,缺血性卒中抗栓循证治疗,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,9,缺血性卒中抗栓循证治疗,链激酶（,SK,）,研究,药物,剂量,治疗窗,结果,Multicenter Acute Stroke Trial-Europe(MAST-E),NEJM 1996;335:145-50,SK,1.5 MU,6h,SK,组出血和死亡率高提前终止试验,Multicenter Acute Stroke Trial-Italy(MAST-I),Lancet 1995;346:1509-14,SK,aspirin,1.5 MU,300 mg/d,6h,SK,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;345:578-9,SK,1.5 MU,4h,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,10,缺血性卒中抗栓循证治疗,动脉溶栓,前循环,大脑中动脉阻塞,后循环,椎基底动脉阻塞,11,缺血性卒中抗栓循证治疗,与安慰剂相比,6h,内予,IA ProUK,经造影证实,MCA M,1,或,M,2,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,12,缺血性卒中抗栓循证治疗,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;5:182-7,13,缺血性卒中抗栓循证治疗,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,.,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,14,缺血性卒中抗栓循证治疗,急性缺血性卒中抗凝治疗,15,缺血性卒中抗栓循证治疗,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,simpler to administer,lower bleeding risk,reduced effect on,IIa,16,缺血性卒中抗栓循证治疗,Summary:trial results,N,drug,results,Canadian,225,Hep IV,no difference,IST,19,435,Hep sc,no difference,TOAST,1281,heparinoid,no difference,large art better at 3 mo?,HK,308,LMWH,dead/dep at 6 mo,FISS,767,LMWH,no difference,TAIST,1486,LMWH,no difference,TOPAS,404,LMWH,no difference among doses,17,缺血性卒中抗栓循证治疗,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,18,缺血性卒中抗栓循证治疗,各卒中亚型急性抗凝治疗,:,小结,CCT,subgrp,N,results,心源性栓塞,1,2,3618,no diff,大动脉硬化,0,4,13,285,1+(?)/3-,后循环,0,3,2318,no diff,TIA,1,0,55,no diff,进展性卒中,2,0,204,no diff,夹层,0,0,286,no diff,静脉血栓,2,0,79,1+/1-,19,缺血性卒中抗栓循证治疗,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,20,缺血性卒中抗栓循证治疗,急性缺血性卒中阿司匹林治疗,21,缺血性卒中抗栓循证治疗,International Stroke Strial(IST),ASA 300 mg/d x 2 wks begun within 48 hrs,2 wk endpts,ASA,N=9720,No ASA,N=9715,Recurrent ischemic,2.8%*,3.9%,All recurrent stroke,3.7%,4.6%,Major extracranial bleed,1.1%*,0.6%,Death,9.0%,9.4%,*,p.01,22,缺血性卒中抗栓循证治疗,Chinese Acute Stroke Trial(CAST),Lancet 1997;349:1641,ASA 160 mg/d x4 wks begun within 48 hrs,4 wk endpts,ASA,N=10335,Placebo,N=10320,Recurrent ischemic,1.6%*,2.1%,All recurrent stroke,3.2%,3.4%,Major extracran bleed,0.8%*,0.6%,Death,3.3%*,3.9%,*,p.05,23,缺血性卒中抗栓循证治疗,小结,基于,IST,和,CAST,阿司匹林在急性缺血性卒中后,2-4,周内，每,1000,例患者中有,10,人可减少死亡和复发。,24,缺血性卒中抗栓循证治疗,非心源性卒中二级预防：抗栓治疗,25,缺血性卒中抗栓循证治疗,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,dipyridamole,),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,.,26,缺血性卒中抗栓循证治疗,Aspirin,27,缺血性卒中抗栓循证治疗,高剂量阿司匹林随机对照试验,#,Study,ASA dose,#of pts,Age,f/u,Prim.Endpoint,%of RR,1,AITIA 1977,Medical group,1300mg,A 88;P 90,60.2,37m,TIA,CI,RI,death,20 only with TIA.,*,P(15.7),2,AITIA 1977 surgical group,650mg,A 65;P 60,60.3,?,TIA,CI,RI,death,Same as medical,*P(15.7),3,CCSG 1978,ASA+SP,1300mg,A 144;P 139,?,26m,TIA,S,death,-6 to 31%,*P(7.6),4,Reuther 1978,1500mg,A 29;P 29,59,24m,TIA,S,NS,*P(8.3),5,AICLA 1983,ASA+DP,990mg,A 198;P 204,63.5,36m,Fatal;nonfatal CI no TIA included,41,*P(7.5),6,Danish CS 1983,1000mg,A 101;P 102,59,25m,S or Death,-77,*P(9.6),7,Swedish CS 1987,1500mg,A 253;P 252,68,24m,S or Death,0,*P(10.9),*,Risk of vascular events(death,stroke,MI)in the control group,28,缺血性卒中抗栓循证治疗,低剂量阿司匹林随机对照试验,#,Study,ASA dose in mg.,#of pts,Age,F/u,Prim.Endpoint,%in RR,1,Danish Low 1988(post CEA),50-100,A150,P151,58.9,25,TIA,S,MI,vascular death,11%(NS),*P(7.3),2,UK TIA 1991,1200,300,Placebo,815,806,814,59.8,48,Major S,MI,Vasc.Death,15%vs P;NS between doses,*P(5.7),3,SALT 1991,75,A676,P684,66.9,32,S or death,16%,*P(10.6),4,ESPS 2,50,A1649,P1649,66.7,24,S,death or both,18%,*P(15.8),*,Vascular events(death,MI,stroke)in placebo.*stroke in placebo,29,缺血性卒中抗栓循证治疗,Antiplatelet Trialists,100,000 pts from 145 trials.,All antiplatelet agents were included.,Clumped all vascular events together.,Overall 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.,30,缺血性卒中抗栓循证治疗,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 300 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 indefinitely.”,FDA.,Federal Register,.1998;63:56802.,31,缺血性卒中抗栓循证治疗,Ticlopidine,32,缺血性卒中抗栓循证治疗,TASS Study:Efficacy*,3-year study endpoints,N=3,069.,Endpoint,Stroke,Stroke,MI,or,vascular death,RRR,21%,9%,(P,=0.024),Hass et al.,N Engl J Med,.1989;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),33,缺血性卒中抗栓循证治疗,Ticlopidine(%),Aspirin(%),Diarrhea,Rash,Nausea,Gastritis,ulcer,GI bleeding,Severe neutropenia (ANC 450/mm,3,),Cerebral hemorrhage,20.4*,11.9*,11.1,2.1,0.9*,0.6,9.8,5.2,10.2,6.0*,0.0,0.7,*,P,0.05,TASS Study:Side Effects,Adapted from Hass et al.,N Engl J Med,.1989;321:501.,34,缺血性卒中抗栓循证治疗,Clopidogril,35,缺血性卒中抗栓循证治疗,CAPRIE Study,Efficacy of Clopidogrel vs.Aspirin(n=19,185),Primary Outcome:MI,Ischemic Stroke,or Vascular Death,Months of Follow-Up,Cumulative,Event Rate(%),0,4,8,12,16,Clopidogrel,Aspirin,0,3,6,9,12,15,18,21,24,27,30,33,36,Aspirin,5.83%,5.32%,Clopidogrel,Event Rate per Year,*,P,=0.043,CAPRIE Steering Committee.Lancet 1996;348:1329-1339.,ARR=0.51,NNT=1/0.005=196,36,缺血性卒中抗栓循证治疗,Clopidogrel(%),ASA(%),GI complaints,Any bleeding disorder,Rash,Diarrhea,GI bleeding,Intracranial hemorrhage,1.90,1.20,0.90*,0.42,0.52,0.21,2.41*,1.37,0.41,0.27,0.93*,0.33,*,P,0.05,CAPRIE Steering Committee.,Lancet,.1996;348:1329-1339.,Side Effects causing discontinuation of drug,CAPRIE Study,37,缺血性卒中抗栓循证治疗,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,38,缺血性卒中抗栓循证治疗,The Second European Stroke Prevention Study:ESPS-2,Tested efficacy of ASA/ER-DP for secondary stroke prevention,Addressed clinical questions,Does 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-DP well tolerated?,The ESPS-2 Group.,J Neurol Sci,.1997;151:S3.Diener et al.,J Neurol Sci,.1996;143:1.,39,缺血性卒中抗栓循证治疗,ESPS-2 Results:Stroke Rates at 24 Months,Placebo,ASA,ER-DP,ASA/ER-DP,0,4,8,12,16,15.2%,12.5%,12.8%,9.5%,Incidence(%),ARR=5.7 over Placebo,NNT=1/0.057=17.5,40,缺血性卒中抗栓循证治疗,ESPS-2:Side Effect Profile,Placebo ASA ASA+ED,GI 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 4mm,Level III:benefit,34 patients with,mobile atheroma,Level III:benefit,Ferrari E et al JACC 1999;33:1317-22,55,缺血性卒中抗栓循证治疗,主动脉弓粥样硬化,Tunick P et al Am J Cardiol 2002;90:1320-5,Level III evidence:benefit of statins,56,缺血性卒中抗栓循证治疗,主动脉弓粥样硬化,:OAC,Tunick P et al Am J Cardiol 2002;90:1320-5,Level III evidence:no benefit of OAC,57,缺血性卒中抗栓循证治疗,主动脉弓粥样硬化,:APA,Tunick P et al Am J Cardiol 2002;90:1320-5,Level III evidence:no benefit of APA,58,缺血性卒中抗栓循证治疗,主动脉弓粥样硬化,:,他汀类,Tunick P et al Am J Cardiol 2002;90:1320-5,Level III evidence:benefit of statins,59,缺血性卒中抗栓循证治疗,1 stroke prevention,Retrospective data show no benefit of OAC for native valve endocarditis,benefit for prosthetic valve endocarditis,1-5,2 stroke prevention:,No data,感染性心内膜炎,1,Davenport et al Stroke 1990;21:993-9,2,Paschalis et al Eur Neurol 1990;30:87-9,3,Yeh et al Circulation 1967;35:I77-81,4,Delahaye et al Eur Heart J 1990;11:1074-8,5,Wilson et al Circulation 1978;57:1004-7,Level V evidence,60,缺血性卒中抗栓循证治疗,?Pathogenesis:fibrin thrombi deposits on valves assoc with coagulopathy(usually DIC),Reported incidence of embolism varies(14-91%),Rx:Retrospective data suggest benefit of heparin,but not OAC,1-3,68%with recurrent emboli when heparin d/cd,ICH risk lower than in infective endocarditis,1,Rogers et al Am J Med 1987;83:746-56,2,Lopez et al Am Heart J 1987;113:773-84,3,Sack 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;,benefit of heparin in Trousseau syndrome(mainly with DIC),61,缺血性卒中抗栓循证治疗,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-.64),Bleeding2.8 (1.7-4.8),Major bleeding OAC 2.8%/yr vs.ASA 0.9%/yr,Level I Evidence:benefit of OAC,62,缺血性卒中抗栓循证治疗,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 at 3.0”,63,缺血性卒中抗栓循证治疗,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,4,1,Med Research Council BMJ 1969;1:335-42,2,Drapkin 222:541-8,3,VA Coop Study JAMA 1973;225:724-9,4,Vaitkus 22:100-9,65,缺血性卒中抗栓循证治疗,心肌梗死后一级预防,:,短期抗凝,Post-thrombolytic era,baseline rates of death,reinfarction,stroke,&PE markedly lower with thrombolytics&ASA,addition of heparin/LMWH may decrease mural thrombus formation,but increases risk of major bleeding without further reducing stroke risk,1,Collins et al BMJ 1996;313:652-9,2,Collins et al NEJM 1997;336:847-60,3,FRAMI Kontny et al JACC 1997;30:962-9,4,SCATI Lancet 1989;2:182-6,5,Gissi-2 Vecchio et al Circulation 1991;84:512-9,66,缺血性卒中抗栓循证治疗,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 incidence,Significantly increase incidence of major bleeding,Anand 282:2058-67,67,缺血性卒中抗栓循证治疗,Modified from Anand 282:2058-67,But no benefit relative to ASA,Incidence of stroke,and significant increase in major bleeding,68,缺血性卒中抗栓循证治疗,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%,69,缺血性卒中抗栓循证治疗,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 AC et al JACC 1985;6:534-538),70,缺血性卒中抗栓循证治疗,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 WARSS,Agree to have additional TEE,Treatment:Warfarin(target INR 1.4-2.8,mean 2.1)vs.aspirin 325 mg,1 endpoint:Recurrent ischemic stroke or death within 2 years,601 patients,42%with cryptogenic stroke as qualifying event,34%with PFO,71,缺血性卒中抗栓循证治疗,PICSS,Level II Evidence:,No difference from aspirin,overall or in any subgroup,No increased event rate in PFO+ASA vs.PFO only,No increased rate with larger PFO size,72,缺血性卒中抗栓循证治疗,Rheumatic MV dz:,Level,III,-,Benefit,over no OAC,Aortic arch atheroma:,Level,III,-,Benefit,over APA in 1 study;,No benefit,of OAC or APA in another(but benefit of statins),Infective endocarditis:,Native valve:Level,V,-,No benefit,Prosthetic valve:Level,V,-,benefit,NBTE:,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(INR 1.4 2.8),MVP:,Level,V,Not completely effective,Atrial 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 effective,No data,Aortic valve disease,Prosthetic heart valves,MI,LV dysfunction,口服抗凝剂（,OAC,）二级预防,:,小结,73,缺血性卒中抗栓循证治疗,Mechanical prosthetic valve:,Level,I,-,Benefit,of OAC+low dose ASA over OAC alone,Bioprosthetic valve:,Level,V,-,Benefit,over no OAC in 1,st,6 weeks after valve replacement,MI:,Level,I,-No benefit over ASA,LVEF 40%:,Level,III,-,Benefit,?INR over ASA,LV aneurysm:,low risk,for,1,occurrence,口服抗凝剂（,OAC,）一级预防,:,小结,74,缺血性卒中抗栓循证治疗,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 dysfunction,WARCEF,(Warfarin vs.Aspirin in Reduced Cardiac EF),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 atheroma,PFO:,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),75,缺血性卒中抗栓循证治疗,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；,76,缺血性卒中抗栓循证治疗,结语,2,3h,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,77,缺血性卒中抗栓循证治疗,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。,78,缺血性卒中抗栓循证治疗,