【精品PPT医学课件】InStent Thrombosis支架内血栓.ppt

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1、支架内血栓In-Stent Thrombosis,Definite/Confirmed（肯定的）Acute coronary syndrome ANDAngiographic confirmation of thrombus or occlusion ORPathologic confirmation of acute thrombosisProbable（可能的）Unexplained death within 30 daysTarget vessel MI without angiographic confirmation of thrombosis or other identified

2、 culprit lesionPossible（不能排除的）Unexplained death after 30 days,ARC 支架内血栓定义,支架内血栓的预后,Similar mortality observed for SES and BMS thrombosis,Pooled Data from RAVEL,SIRIUS,C-SIRIUS,E-SIRIUS,支架内血栓发生时间,ST=stent thrombosis;SAT=subacute stent thrombosis;LST=late stent thrombosis;VLST=very late stent thrombos

3、is.Adapted from Bhatt.J Invasive Cardiol.2003;15(suppl B):3B.,Stent Thrombosis(%),支架内血栓与抗凝、抗血小板治疗,ASA und Ticlopidine,ASA und Anticoagulation,ASA und Clopidogrel,ASA=Acetylsalicylic acidDES:Drug-eluting stent,Bare Metal Stent,Prasugrel?,DES肯定的ST发生率:Bern-Rotterdam Cohort Study Daemen,Wenaweser et al.

4、Lancet 2007;369:667-78,N=8146,0,1,2,3,4,Time since PCI in years,0,1,2,3,4,5,Cumulative incidence,%,Incidence density1.0/100 pt years,3.3%,3.5,0.53%(95%CI=0.44-0.64)/year,192 definite ST cases,DES肯定的ST发生率:Bern-Rotterdam Cohort Study 4 YearsWenaweser P et al.J Am Coll Cardiol 2008,52,1134-,0.52%(95%CI

5、=0.42-0.62)/year between 30 days and 5 years,DES肯定的支架内血栓发生率:Bern-Cohort Study 5 YearsWenaweser P et al.ESC 2008,DES vs BMSA cohort of 9,175 patients treated with either BMS or DES(SES or PES),all patients with angiographically documented ST were identified as cases,Early Stent Thrombosis,RR=0.7695%C

6、I=0.30-1.80P=0.55,RR=0.8095%CI=0.32-2.03P=0.79,Meta-analysisSES vs BMSBavry A et al.Am J Card 2005,Meta-analysisPES vs BMSStone G et al.NEJM 2007,%,%,Very Late ST 1 Year(Per Protocol),P=0.75,P=0.02,%,P=0.30,P=0.03,%,Stone G et al.NEJM 2007;356:998-1008,Kastrati A et al.NEJM 2007;356:1030-9,Sirolimus

7、-Eluting Stent,Paclitaxel-Eluting Stent,SIRTAX Definite ST 4 YearsWindecker S et al ESC 2008,2.0%,1.8%,2.8%,2.4%,3.7%,3.4%,Cumulative Incidence of Definite STin LEADERS(BES vs.SES)Windecker et al.Lancet,2008,372,1163-,Overall Incidence of ST with DES,ENDEAVOR,XIENCE,BIOMATRIX,High Risk of ST in All-

8、Comer Patient Population and STEMI Patients,%,支架内血栓的病因,STENT THROMBOSIS,PatientGenetic PolymorphismReduced LV-EFAcute Coronary SyndromeHematology Disorder,DrugsResistanceDrug-drug InteractionDuration of AntiplateletTreatement,Vessel ReactionVessel RemodelingHypersensitivity ReactionDelayed Healing,早

9、期支架内血栓的预测因素:残留夹层/撕裂,Bare Metal StentsMACE 30 daysSchhlen H et al.Circulation 1998,N=2,894,Drug-Eluting StentsMACE 30 daysBiondi-Zoccai G et al.EHJ 2006,N=2,418,%,P=0.01,P=0.01,Residual Dissection:Independent Predictor of MACE(OR=2.9),早期支架内血栓IVUS预测因素 With the Use of Sirolimus-Eluting StentsFujii K et

10、 al.J Am Coll Cardiol 2005;45:995-8,Minimal Stent CSA,P0.001,mm2,Stent Expansion,Residual Stenosis,%,P0.001,Stent Underexpansion and Residual Reference Segment Stenosis:Independent Predictors of Early Stent Thrombosis!,P0.001,支架内血栓预测因素药物反应异常 Wenaweser P et al.JACC 2005;45(11):1748-52,服药后血小板活性与DES ST

11、的关系Buonamici P et al JACC 2007,p0.001,p0.001,p0.001,p=ns,Iakovou et alJAMA 2005,Park et alAm J Card 2006,Airoldi et alCirculation 2007,Kuchulakanti et alCirculation 2006,OR=89.8(29.9-270),HR=19.2(5.6-65.5),HR=13.7(4.0-46.7),OR=4.8(2.0-11.1),Odds/Hazard Ratio,过早停用抗血小板药物是支架内血栓的重要预测因素,支架内血栓发生时的抗血小板治疗 B

12、ern-Rotterdam Cohort Study 5 YearsWenaweser P et al.ESC 2008,Triton TIMI 38 Prasugrel vs.Clopidogrel in ACS Patients With StentsWiviott SD et al.Lancet 2008;371:1353-63,Overall Stent Thrombosis,Early Stent Thrombosis,Late Stent Thrombosis,Park et alAm J Card 2006,Airoldi et alCirculation 2007,Iakovo

13、u et alJAMA 2005,Machecourt et alJACC 2007,OR=1.03(1.00-1.05),OR=1.01(1.00-1.03),OR=2.75(1.55-4.88),Odds Ratio,支架内血栓的预测因素-支架长度,OR=1.02(1.00-1.04),OR=1.08(1.06-1.1),De la Torre et alJACC 2008,Roy et alJ Interv Card 2007,Kuchulakanti et alCirculation 2006,OR=4.4(2.0-10.0),Odds Ratio,支架内血栓的预测因素-分叉病变,OR

14、=2.4(1.1-5.6),Iakovou et alJAMA 2005,OR=6.4(2.9-14.1),Ong et alJACC 2005*,OR=12.9(4.7-35.8),*in setting of AMI,Joner et al JACC 2006,Park et alAm J Card 2006,Daemen et alLancet 2007,Urban et alCirculation 2006,OR=12.4(1.7-89.7),OR=2.3(1.3-4.0),OR=1.8(1.1-2.7),Odds/Hazard Ratio,支架内血栓的预测因素-ACS,De la T

15、orre et alJACC 2008,HR=2.6(1.3-4.9),Impact of Thrombus Burden on Risk of ST With DES in Patients With STEMISianos G et al.J Am Coll Cardiol 2007;50:573-83,Independent Predictors of ST,Kuchulakanti Circ 2006,Urban Circ 2006,IakovouJAMA 2005,DaemenLancet 2007,Machecourt JACC 2007,OR=2.0(0.8-4.9),OR=2.

16、8(1.7-4.3),HR=3.7(1.7-7.9),HR=2.0(1.1-3.8),OR=2.7(1.4-5.2),Odds/Hazard Ratio,支架内血栓的预测因素-糖尿病,IijimaAm J Card 2007,HR=2.2(1.1-4.3),HR=1.75(1.0-3.0),De la TorreJACC 2008,晚期支架内血栓的可能原因,Chronic inflammatory reaction to the polymer or drugHypersensitivity to the polymer or drugFailure of stents to complete

17、ly reendothelialize completelyLate incomplete stent appositionDisease progression,多聚物高敏,获得性晚期支架贴壁不良,Baseline 8 mo follow-up,SIRIUS Trial:7/80(8.7%)patients,no 12-month MACE Ako J.et al.JACC 2005;46:1002-5,Cook et al.Circulation 2007,Kotani et al.JACC 2006,Joner et al.JACC 2006,Togni et al.JACC 2005,

18、Abnormal Vasomotion,Delayed Healing,Delayed Endothelialization,Vessel Remodeling,DES后病生理机制,Endothelialization,小结,DES支架内血栓发生率：Early:0.5%-1.6%Late/Very late:0.3%-0.6%预测因素Residual dissection,stent underexpansionDiabetes,ACS,bifurcation stenting,stent length,thrombus burden,late aquired stent malapposit

19、ion,ineffective platelet inhibition,支架内血栓的预防,高危病人的辨认避免过度支架长支架,分叉支架,支架重叠支架植入的理想结果 无残留撕裂/夹层支架膨胀良好增加抗血小板治疗的有效性高危病人评估抗血小板药物的反应性再狭窄低危病人中使用BMS,专家共识,FDA DES Panel Meeting,There is an increase in“very late”(1 yr)stent thrombosis associated with current DES2-4 per 1000 pts per year(?continous hazard,?patient

20、 and lesion predictors)Data from multiple sources indicate thatDES are associated with delayed healingresponses and increased inflammationThe causes of late DES thrombosis are multi-factorial;device,procedural,and patientfactors(often multiple=perfect storm),专家共识,FDA DES Panel Meeting,There may be a

21、 link between post-DES reduced neo-intimal hyperplasia(late loss)and delayed late healing responses which contributes to late stent thrombosis DES stent thrombosis is highly definition dependent;need for revised standardizeddefinitions and adjudication methods(ARC)to facilitate inter-study compariso

22、ns,专家共识,“Off-label DES use increased incidence of late DES thrombosis and death/MI cw“on-label”,butinadequate controls;results inconsistent!Few RCTs(underpowered);FDA sanctioned registries=insufficient sample size and FU,represents major data gap and source of concernLarge population studies(SCAAR)f

23、raught with methodologic flaws(e.g.risk adjustment issues),专家共识,Duration of dual anti-platelet therapy should extend beyond the present product labelsOne year is reasonable compromise(esp.for“off-label”DES use)Must balance against the increased risk ofbleeding with dual anti-platelet therapyAddition

24、al studies immediately required tobetter clarify optimal anti-platelet therapy,专家共识,Assess patient and lesion characteristics to establish restenosis risk profileDetermine relative value of DES vs.BMS inevery patient(no more“unrestricted”use)Consider both on-label and off-label situations(ironically

25、,off-label use scenarios may be more compelling)Increased restenosis risk=favor DESIncreased safety concerns=favor No DES,专家共识,Assess patient factors which may preclude long-term(at least one year)dual AP therapyPlanned or possible intercurrent surgeryBleeding Hx or tendenciesOther concomitant medic

26、ations(e.g.coumadin)Socio-economic factors which may affect Plavix compliance,专家共识,Consider alternatives to DES,if risk-benefit assessments prove unfavorableCABG unprotected LM disease,complex MVD(esp.diabetics),recurrent ISR(esp.VBT)BMS Plavix dependence concerns,large(4mm diameter)vessels,?AMI pts

27、,?low restenosis risk lesionsBalloon PCI sidebranch in bifurcations(provisional stent only),small vessels in distal locations,专家共识,Optimize DES implantation techniquesAdequate lesion preparation(pre-dilatation)High pressure implantation methodologies(like previous BMS strategies)Avoid undersizing an

28、d inflow/outflow obstruction(mod stenoses or dissections)Implant stent edges into normal references segmentsConsider IVUS guidance(esp.LAD),专家共识,Careful explanations and open communication with patients and familiesCareful pre-treatment historyDiscussion with EVERY pt re:risks and benefits of DES vs.alternative therapiesOngoing(post-Rx)communication and careful FU re:dual AP compliance(instructions=NO Plavix discontinuation without MD approval)!,DES 风险&获益,治疗1000个病人可以预防100个再狭窄同时可以预防10个再狭窄相关的心肌梗死可能会因为晚期支架内血栓增加5个心肌梗死获益风险,