美敦力新一代药物洗脱支架的安全性与有效性.ppt

EndeavorSprint美敦力新一代药物洗脱支架的安全性与有效性,中国医大一院心内科齐国先,支架模块设计,PC生物相容性多聚物,高亲脂性的“Zotarolimus”,Sprint输送系统-新,EndeavorSprint,支架输送系统,Endeavor,EndeavorSprint在Endeavor基础上改良,EndeavorSprint新工艺出色的Sprinter球囊输送性用于支架,广受好评的支架平台沿用Endeavor支架的钴合金模块设计,无棱角金属丝最小化血管内皮损伤,通过外径,头端外径,*Medtroniccrossingprofiletestingconductedwith3.5mmx18mmEndeavorSprint,CYPHERSELECTPlus,XIENCEstents;and3.5mmx20mmTaxusLibertestent.Testingconductedwith3.5mmX18mmEndeavorSprint,XIENCE,CYPHERSELECTPlusstents;3.5mmX20mmTaxusLibertestent.TestdataonfileatMedtronic,Inc.,小外径设计为挑战性病变的治疗提供便利,EndeavorSprint通过外径和输送性,EndeavorSprint进一步减小推送杆尺寸:可进行更复杂的器械操作,EndeavorSprint最佳输送有效性利于临床挑战更复杂病例,EndeavorSprint在Endeavor高输送性基础上更加大幅度提高,优化药物洗脱支架输送系统,药物洗脱支架长期应用：安全性与有效性,药物支架新看点,过往晚期丢失TLR(含非临床驱动）血栓(ARC定义)9-12个月,现在临床终点TVF临床驱动TLR血栓(ARC定义)心源性死亡/心梗1年,DES安全性:支架血栓,短期和长期安全性分析:支架血栓发生的时间点和预测因子,1year,急性1天,晚期1个月1天-1个月,早期1年,早期支架血栓30天以内,1个月,1年,晚期1个月1年,极晚期支架血栓超过1年,Wenaweseretal;JAmCollCardiol2019;52:1134-40Maurietal;NEnglJMed2019;356:1020-9.,TimesincePCIinyears,CumulativeIncidence,%,5,4,3,2,1,0,0,1,2,3,4,2,极晚期支架血栓第一代DES随访4年累计发生率,1年以内Endeavor:0.6%Driver:1.3%,1年以后(VLST)Endeavor:0.1%Driver:0.2%,1.5%,0.7%,P=0.071,0%,2%,4%,6%,8%,10%,0,90,360,720,1440,ARCDef/ProbST,180,270,450,540,630,810,900,990,1080,1170,1350,1260,Days,ENDEAVORPooledSafety:Mauri,TCT2019.EI(5yr),EII(4yr),EIICA(4yr),EIII(3yr),EIV(2yr)356:1020-1029.3.SerruysPWetal.ACC20193.StoneGWetal.PCR2019.,DES研究进展:极晚期支架血栓ARC(肯定/可能)支架血栓标志性分析,7.0%,4.6%,ENDEAVORPooledSafety:Mauri,TCT2019.EI(5yr),EII(4yr),EIICA(4yr),EIII(3yr),EIV(2yr)JAmCollCardiol2019;52;789-90,17个患者44个重叠ZES6个月随访(24,076个金属丝分析)ZES无贴壁不良,100%内皮覆盖;无附壁血栓Guagliumietal;ESC2019,541ZESpts8个月随访0.4%晚期贴壁不良;无正性重塑;均匀的新生内膜分布Fitzgeraldetal;StanfordIVUScorelab,ZES(n=20)vs.SES(n=20)vs.BMS(n=10);乙酰胆碱试验6个月;ZES较SES改善了内皮功能(P0.001),和BMS结果相似Kimetal;ACC2019,ENDEAVOR安全性涉及因素人体结果,DES有效性：靶病变血运重建,短期和长期有效性分析:TLR时间点和预测因子,药物洗脱支架长期应用：安全性与疗效,9-12Months,TLR1year,靶病变血运重建1年以前和1年以后,FreedomfromTLR,100%,90%,95%,0,30,60,90,120,150,180,210,240,270,300,330,360,TimeafterInitialProcedure(days),ENDEAVORIV360天无TLR生存率,关键试验患者:DES组相似的基线特征和形态学,SiriusTrial,Holmesetal,Circulation2019TAXUSIV,Stoneetal,Circulation2019EndeavorII,Fajadetetal.Circulation.2019;114:98-806.,4.6,4.1,ENDEAVORII,TAXUSIV,SIRIUS,3.0,0.62,0.39,0.17,ENDEAVORII,TAXUSIV,SIRIUS,0.36,0.23,0.24,9个月TLR(%),晚期丢失(mm),支架内LL(mm),节段内LL(mm),*12monthanalysisDatafromdifferentclinicaltrialsarenotsuitableforcomparison.,SIRIUS.Mosesetal.NEJM.2019;349:1315-1323.TAXUSIV.Stoneetal.NEJM.2019;350:221-231.SIRIUSdiabetessubset.Circulation.2019;109:2273-2278.TAXUSIVdiabetessubset.JAmCollCardiol.2019;45:1172-1179.Fajadetetal.Circulation.2019;114:98-806.,关键试验:晚期丢失vs.TLR1-2%的差别,DES研究进展4年TLR标志性分析,EndeavorII(n=581/598),Sirius(n=501/525),TaxusIV(n=618/650),Days,%TLR,4YearClinicalResultsofTAXUSIV,Stone,ACC20194yearOutcomesintheSiriusTrial,Leon,TCT2019EndeavorII4year:Fajadetetal.PCR2019,9-12月,TLR1年,靶病变血运重建TLR1年以内和1年以后,多聚物影响长期的安全性有效性,持久疗效源自理想的内皮修复拟生态和生物相容性的PC多聚物最小化其长期致炎性临床前研究显示快速、完全和功能完好的内皮修复,28天兔子动脉粥样硬化血管的内皮修复Atheroscleroticrabbitmodel,representativehealingat28days.PresentedbyRenuVirmani,CRT,2019.,n/a,EndeavorII(n=581/598),Sirius(n=501/525),TaxusIV(n=618/650),关键试验的TLR:DES组每一年的TLR随访,5.9,6.5,7.2,7.2,R,2,=0.9524,0,2,4,6,8,10,1,2,3,4,5,YearsofFollow-up,TLR(%),4.9,6.8,7.9,9.4,6.3,R,2,=0.9762,0,2,4,6,8,10,1,2,3,4,5,YearsofFollow-up,TLR(%),4.4,5.6,6.9,7.8,9.1,R,2,=0.9973,0,2,4,6,8,10,YearsofFollow-up,TLR(%),1,2,3,4,5,4YearClinicalResultsofTAXUSIV,Stone,ACC20194yearOutcomesintheSiriusTrial,Leon,TCT2019EndeavorII4year:Fajadetetal.PCR2019,DES研究进展随访4年TLR标志性研究,EndeavorII(n=581/598),Sirius(n=501/525),TaxusIV(n=618/650),Days,%TLR,4YearClinicalResultsofTAXUSIV,Stone,ACC20194yearOutcomesintheSiriusTrial,Leon,TCT2019EndeavorII4year:Fajadetetal.PCR2019,第一代DES在置入1年后TLR危险因素持续存在,1.Maurietal.TCT2019.2.Stone,G.etal.NEnglJMed.2019;356:998-1008,累积DES分析基线形态学,6.7%,7.8%,310d,940d,10.1%,518d,0%,5%,10%,15%,20%,25%,30%,0,180,360,540,720,900,1080,1260,1440,随访天数,TLR,Endeavor,Cypher,Taxus,Resultscomefromseparateclinicaltrials.Datamaydifferinahead-to-headcomparison.1.Maurietal.TCT.2019.ENDEAVORPooledSafety:EI(5yr),EII(4yr),EIICA(4yr),EIII(3yr),EIV(2yr)356:998-1008.,DES试验4年随访数据Endeavor,Taxus和Cypher支架TLR发生时间点差异,TLR(%),N=322,N=725,4years,EI,EII,EIICA,EIII,EIV,E-PKN=(2132),N=2132,Endeavor试验累积数据分析:第1和第4年随访高危亚组TLR对照,2.5mmRVD,糖尿病,AllPatients,20mmLesions,eFIVE12monthdata:Rothamnetal.PCR2019,1year,N=555,3.0%,2.5%,2.0%,1.5%,1.0%,0.5%,0.0%,ARC(Def/Prob),DES研究进展,1.Maurietal.TCT2019.2.MauriLetal.NEnglJMed.2019;356:1020-1029.3.SerruysPWetal.ACC2019.3.StoneGWetal.PCR2019.,TLRLandmarkto4years,第一代DES在置入1年后TLR危险因素持续存在导致晚期追赶,ARCDef/ProbSTLandmarkAnalysis,4YearClinicalResultsofTAXUSIV,Stone,ACC2019.4yearOutcomesintheSiriusTrial,Leon,TCT2019.EndeavorII4year:Fajadetetal.PCR2019.,安全性尽管1年后仅39%的Endeavor患者服用双联