支架内血栓李建平.ppt

支架内血栓支架内血栓In-Stent Thrombosis北京大学第一医院北京大学第一医院 李建平李建平•Definite/Confirmed （肯定的）（肯定的）–Acute coronary syndrome AND–[Angiographic confirmation of thrombus or occlusion OR–Pathologic confirmation of acute thrombosis]•Probable （可能的）（可能的）–Unexplained death within 30 days–Target vessel MI without angiographic confirmation of thrombosis or other identified culprit lesion•Possible （不能排除的）（不能排除的）–Unexplained death after 30 daysARC 支架内血栓定义支架内血栓定义支架内血栓的预后支架内血栓的预后SES (N=13)BMS (N=15)Death45Myocardial Infarction1313Fatal MI44Q Wave MI85Non-Q Wave MI 58Similar mortality observed for SES and BMS thrombosisSimilar mortality observed for SES and BMS thrombosisPooled Data from RAVEL, SIRIUS, C-SIRIUS, E-SIRIUSPooled Data from RAVEL, SIRIUS, C-SIRIUS, E-SIRIUS支架内血栓发生时间支架内血栓发生时间ST = stent thrombosis; SAT = subacute stent thrombosis;LST = late stent thrombosis; VLST = very late stent thrombosis.Adapted from Bhatt. J Invasive Cardiol. 2003;15(suppl B):3B.Stent Thrombosis (%)支架内血栓与抗凝、抗血小板治疗支架内血栓与抗凝、抗血小板治疗ASA und TiclopidineASA und AnticoagulationASA und ClopidogrelDESASA = Acetylsalicylic acidDES: Drug-eluting stent Bare Metal StentPrasugrel?BMS支架内血栓发生率支架内血栓发生率Days108642003060120 600NEarly1.2%(N=71)Late0.4%(N=24)Study population 1995-2002-6,058 patients undergoing PCI with BMSWenaweser P et al. EHJ 2005N=1,191N=1,855N=361N=6,058Stent Thrombosis (%)DES肯定的肯定的ST发生率发生率:Bern - Rotterdam Cohort Study Daemen, Wenaweser et al. Lancet 2007;369:667-780.6% / yearEarly ST 91 pts(60%)Late ST 61 pts (40%)Incidence density:1.3 / 100 patient yearsN=814601234Time since PCI in years012345Cumulative incidence, %Months112243648Cumulative incidence, %1.21.62.12.73.3Patients at risk75387210516427901051Incidence density1.0 / 100 pt years3.3%3.50.53% (95% CI=0.44-0.64)/ year192 definite ST casesDES肯定的肯定的ST发生率发生率:Bern-Rotterdam Cohort Study @ 4 YearsWenaweser P et al. J Am Coll Cardiol 2008, 52, 1134-0.52% (95% CI=0.42-0.62)/ year between 30 days and 5 yearsDES肯定的支架内血栓发生率肯定的支架内血栓发生率:Bern-Cohort Study @ 5 YearsWenaweser P et al. ESC 2008Favours DESFavours BMS>180 days31-180 days 0-30 daysTime after PCI.1.2.512510 2050 100Odds RatioFavors DESFavors BMS.1.2.5125102050 100Odds RatioAdjusted Resultswith interaction terms for time since PCIEarly period: 0-30 daysOR 0.59, 95% CI .35 - 1.01Late period: 31-180 daysOR 0.52, 95% CI .16 – 1.75Very late period: > 180 daysOR 9.4, 95% CI 2.56 – 34.70Wenaweser et al. ACC 2007DES 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 Very Late ST > 1 Year (Per Protocol) P=0.75P=0.02%P=0.30P=0.03%Stone G et al. NEJM 2007;356:998-1008Kastrati A et al. NEJM 2007;356:1030-9Sirolimus-Eluting StentPaclitaxel-Eluting StentSIRTAX – Definite ST @ 4 YearsWindecker S et al ESC 20082.0%1.8%2.8%2.4%3.7%3.4%1-year HR1.12 [0.46, 2.76]P = 0.012-year HR0.86 [0.40, 1.87]P = 0.713-year HR0.90 [0.47, 1.73]P = 0.754-year HR1.06 [0.57, 1.95]P = 0.86SES 4.2%PES 3.9%Overall Incidence of ST with DESCYPHERTAXUSENDEAVOR XIENCE BIOMATRIX0.40.30.70.51.61.40.8TAXUS IITAXUS IVTAXUS VTAXUS VIREALITYSIRTAXISAR-DM10.50.81.9Endeavor IEndeavor IISpirit IIILeaders0.21.120.61.80.800123SIRIUSE-SIRIUSC-SIRIUSREALITYSIRTAXARTS IIISAR-DM%High Risk of ST in All-Comer Patient Population and STEMI Patients%支架内血栓的病因支架内血栓的病因STENT THROMBOSISStentDesign/LengthPolymerSurfaceDrugsLesionVessel SizeThrombusInterventionResidual DissectionIncomplete Stent AppositionAntithromobotic MedicationPatientGenetic PolymorphismReduced LV-EFAcute Coronary SyndromeHematology DisorderDrugsResistanceDrug-drug InteractionDuration of AntiplateletTreatementVessel ReactionVessel RemodelingHypersensitivity ReactionDelayed Healing早期支架内血栓的预测因素早期支架内血栓的预测因素:残留夹层残留夹层/撕裂撕裂Bare Metal StentsMACE @ 30 daysSchühlen H et al. Circulation 1998N=2,894Drug-Eluting StentsMACE @ 30 daysBiondi-Zoccai G et al. EHJ 2006N=2,418%P=0.01P=0.01Residual Dissection: Independent Predictor of MACE (OR=2.9)早期支架内血栓早期支架内血栓IVUS预测因素预测因素 With the Use of Sirolimus-Eluting StentsFujii K et al. J Am Coll Cardiol 2005;45:995-8Minimal Stent CSAP<0.001mm2Stent ExpansionResidual Stenosis%P<0.001Stent Underexpansion and Residual Reference Segment Stenosis:Independent Predictors of Early Stent Thrombosis!P<0.001支架内血栓预测因素支架内血栓预测因素药物反应异常药物反应异常 Wenaweser P et al. JACC 2005; 45(11):1748-52 服药后血小板活性与服药后血小板活性与DES ST的关系的关系Buonamici P et al JACC 2007p<0.001p<0.001p<0.001p=nsIakovou et alJAMA 2005Park et alAm J Card 2006Airoldi et alCirculation 2007Kuchulakanti et alCirculation 2006OR=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过早停用抗血小板早停用抗血小板药物是支架内血栓的重要物是支架内血栓的重要预测因素因素支架内血栓发生时的抗血小板治疗支架内血栓发生时的抗血小板治疗 Bern-Rotterdam Cohort Study @ 5 YearsWenaweser P et al. ESC 2008Park et alAm J Card 2006Airoldi et alCirculation 2007Iakovou et alJAMA 2005Machecourt et alJACC 2007OR=1.03(1.00-1.05)OR=1.01(1.00-1.03)OR=2.75(1.55-4.88)Odds Ratio支架内血栓的支架内血栓的预测因素因素-支架支架长度度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 2007Kuchulakanti et alCirculation 2006OR=4.4(2.0-10.0)Odds Ratio支架内血栓的支架内血栓的预测因素因素-分叉病分叉病变OR=2.4(1.1-5.6)Iakovou et alJAMA 2005OR=6.4(2.9-14.1)Ong et alJACC 2005*OR=12.9(4.7-35.8)*in setting of AMIJoner et al JACC 2006Park et alAm J Card 2006Daemen et alLancet 2007Urban et alCirculation 2006OR=12.4(1.7-89.7)OR=2.3(1.3-4.0)OR=1.8(1.1-2.7)Odds/Hazard Ratio支架内血栓的支架内血栓的预测因素因素-ACS De la Torre et alJACC 2008HR=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;50:573-83Variable Hazard Ratio 95% CIAge0.60.4-0.8Index ST6.22.1-18.9Bifurcation4.11.6-10.0Thrombectomy0.10.01-0.8Large thrombus8.73.4-22.5Independent Predictors of STKuchulakanti Circ 2006Urban Circ 2006IakovouJAMA 2005DaemenLancet 2007Machecourt JACC 2007OR=2.0(0.8-4.9)OR=2.8(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支架内血栓的预测因素-糖尿病糖尿病IijimaAm J Card 2007HR=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晚期支架内血栓的可能原因•Chronic inflammatory reaction to the polymer or drug•Hypersensitivity to the polymer or drug•Failure of stents to completely reendothelialize completely•Late incomplete stent apposition•Disease progression获得性晚期支架贴壁不良获得性晚期支架贴壁不良 Baseline 8 mo follow-upSIRIUS Trial: 7/80 (8.7%) patients, no 12-month MACE Ako J. et al. JACC 2005;46:1002-5Cook et al. Circulation 2007Kotani et al. JACC 2006Joner et al. JACC 2006Togni et al. JACC 2005Abnormal VasomotionDelayed HealingDelayed EndothelializationVessel Remodeling DES后病生理机制Endothelialization 支架内血栓的预防支架内血栓的预防•高危病人的辨认高危病人的辨认•避免过度支架避免过度支架–长支架长支架, 分叉支架分叉支架, 支架重叠支架重叠•支架植入的理想结果支架植入的理想结果 –无残留撕裂无残留撕裂/夹层夹层–支架膨胀良好支架膨胀良好•增加抗血小板治疗的有效性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再狭窄低危病人中使用BMS专家共识专家共识FDA DES Panel MeetingØThere is an increase in “very late” (>1 yr) stent There is an increase in “very late” (>1 yr) stent thrombosis associated with current DESthrombosis associated with current DES•~2-4 per 1000 pts per year (? continous hazard, ~2-4 per 1000 pts per year (? continous hazard, ? patient and lesion predictors) ? patient and lesion predictors)•Data from multiple sources indicate thatData from multiple sources indicate thatDES are associated with delayed healingDES are associated with delayed healingresponses and increased inflammationresponses and increased inflammation•The causes of late DES thrombosis are multi-The causes of late DES thrombosis are multi-factorial; device, procedural, and patientfactorial; device, procedural, and patientfactors (often multiple = perfect storm) factors (often multiple = perfect storm) 专家共识专家共识FDA DES Panel Meeting• •There may be a link between post-DES reduced There may be a link between post-DES reduced neo-intimal hyperplasia (late loss) and delayed neo-intimal hyperplasia (late loss) and delayed late healing responses which contributes to late late healing responses which contributes to late stent thrombosisstent thrombosis • •DES stent thrombosis is highly definition DES stent thrombosis is highly definition dependent; need for revised standardizeddependent; need for revised standardizeddefinitions and adjudication methods (ARC) definitions and adjudication methods (ARC) to facilitate inter-study comparisonsto facilitate inter-study comparisons专家共识专家共识Ø“Off-label DES use – increased incidence of late “Off-label DES use – increased incidence of late DES thrombosis and death/MI cw “on-label”, butDES thrombosis and death/MI cw “on-label”, butinadequate controls; results inconsistent!inadequate controls; results inconsistent! •Few RCTs (underpowered); FDA sanctioned Few RCTs (underpowered); FDA sanctioned registries = insufficient sample size and FU, registries = insufficient sample size and FU, represents major data gap and source of represents major data gap and source of concernconcern•Large population studies (SCAAR) fraught Large population studies (SCAAR) fraught with methodologic flaws (e.g. risk adjustment with methodologic flaws (e.g. risk adjustment issues) issues) 专家共识专家共识ØDuration of dual anti-platelet therapy should Duration of dual anti-platelet therapy should extend beyond the present product labelsextend beyond the present product labels•OOne year is reasonable compromise (esp. forne year is reasonable compromise (esp. for“off-label” DES use)“off-label” DES use)•Must balance against the increased risk ofMust balance against the increased risk ofbleeding with dual anti-platelet therapybleeding with dual anti-platelet therapy•Additional studies immediately required toAdditional studies immediately required tobetter clarify optimal anti-platelet therapybetter clarify optimal anti-platelet therapy专家共识专家共识ØAssess patient and lesion characteristics to Assess patient and lesion characteristics to establish restenosis risk profileestablish restenosis risk profile•Determine relative value of DES vs. BMS inDetermine relative value of DES vs. BMS inevery patient (no more “unrestricted” use) every patient (no more “unrestricted” use) •Consider both on-label and off-label Consider both on-label and off-label situations (ironically, off-label use scenarios situations (ironically, off-label use scenarios may be more compelling)may be more compelling)•Increased restenosis risk = favor DESIncreased restenosis risk = favor DES•Increased safety concerns = favor No DES Increased safety concerns = favor No DES 专家共识专家共识ØAssess patient factors which may preclude long-Assess patient factors which may preclude long-term (at least one year) dual AP therapyterm (at least one year) dual AP therapy•Planned or possible intercurrent surgeryPlanned or possible intercurrent surgery•Bleeding Hx or tendenciesBleeding Hx or tendencies•Other concomitant medications (e.g. Other concomitant medications (e.g. coumadin)coumadin)•Socio-economic factors which may affect Socio-economic factors which may affect Plavix compliance Plavix compliance 专家共识专家共识ØConsider alternatives to DES, if risk-benefit Consider alternatives to DES, if risk-benefit assessments prove unfavorableassessments prove unfavorable•CABG – unprotected LM disease, complex CABG – unprotected LM disease, complex MVD (esp. diabetics), recurrent ISR (esp. VBT) MVD (esp. diabetics), recurrent ISR (esp. VBT) •BMS – Plavix dependence concerns, large BMS – Plavix dependence concerns, large (>4mm diameter) vessels, ? AMI pts, ? low (>4mm diameter) vessels, ? AMI pts, ? low restenosis risk lesionsrestenosis risk lesions•Balloon PCI – sidebranch in bifurcations Balloon PCI – sidebranch in bifurcations (provisional stent only), small vessels in distal (provisional stent only), small vessels in distal locations locations 专家共识专家共识ØOptimize DES implantation techniquesOptimize DES implantation techniques•Adequate lesion preparation (pre-dilatation)Adequate lesion preparation (pre-dilatation)•High pressure implantation methodologies High pressure implantation methodologies (like previous BMS strategies)(like previous BMS strategies)•Avoid undersizing and inflow/outflow Avoid undersizing and inflow/outflow obstruction (mod stenoses or dissections)obstruction (mod stenoses or dissections)•Implant stent edges into normal references Implant stent edges into normal references segmentssegments•Consider IVUS guidance (esp. LAD) Consider IVUS guidance (esp. LAD) 专家共识专家共识ØCareful explanations and open communication Careful explanations and open communication with patients and familieswith patients and families•Careful pre-treatment historyCareful pre-treatment history•Discussion with EVERY pt re: risks and Discussion with EVERY pt re: risks and benefits of DES vs. alternative therapiesbenefits of DES vs. alternative therapies•Ongoing (post-Rx) communication and careful Ongoing (post-Rx) communication and careful FU re: dual AP compliance (instructions = NO FU re: dual AP compliance (instructions = NO Plavix discontinuation without MD approval)! Plavix discontinuation without MD approval)! DES 风险风险 & 获益获益•治疗治疗1000个病人可以预防个病人可以预防100个再狭窄个再狭窄•同时可以预防同时可以预防10个再狭窄相关的心肌梗个再狭窄相关的心肌梗死死•可能会因为晚期支架内血栓增加可能会因为晚期支架内血栓增加5个心肌个心肌梗死梗死•获益获益>风险风险。