美敦力新一代药物洗脱支架的安全性与有效性--PPT课件.ppt

1、中国医大一院心内科中国医大一院心内科 齐国先齐国先2009.5.16 医大一院医大一院支架模块设计支架模块设计PC 生物相容性多聚物生物相容性多聚物高亲脂性的高亲脂性的“Zotarolimus”Sprint 输送系统输送系统-新新Endeavor Sprint支架输送系统支架输送系统Endeavor 2009.5.16 医大一院医大一院2009.5.16 医大一院医大一院通过外径通过外径头端外径头端外径*Medtronic crossing profile testing conducted with 3.5 mm x 18 mm Endeavor Sprint,CYPHER SELECT P

2、lus,XIENCE stents;and 3.5 mm x 20 mm Taxus Liberte stent.Testing conducted with 3.5 mm X 18 mm Endeavor Sprint,XIENCE,CYPHER SELECT Plus stents;3.5 mm X 20 mm Taxus Liberte stent.Test data on file at Medtronic,Inc.2009.5.16 医大一院医大一院中段杆中段杆近段杆近段杆远段杆远段杆两端不透射线标记两端不透射线标记Discrete技术技术:最小化球囊突出最小化球囊突出2009.5.

3、16 医大一院医大一院Endeavor Sprint在在Endeavor 高输送性基础上高输送性基础上更加大幅度提高更加大幅度提高使用3.518mm支架进行测试2009.5.16 医大一院医大一院 2009.5.16 医大一院医大一院2009.5.16 医大一院医大一院 2009.5.16 医大一院医大一院2009.5.16 医大一院医大一院1 year急性1天晚期 1 个月 1天-1个月早期 1年1个月早期支架血栓 30天以内2009.5.16 医大一院医大一院1 个月1 年晚期 1 个月 1年极晚期支架血栓 超过1 年 2009.5.16 医大一院医大一院Wenaweser et al;J

4、 Am Coll Cardiol 2019;52:1134-40Mauri et al;N Engl J Med 2019;356:1020-9.Time since PCI in yearsCumulative Incidence,%543210012342.1%(17)CYPHER Stent(n=878)2.1%(26)TAXUS Stent (n=1401)Cypher&Taxus Pooled Analyses5.7%95%CICYPHER&TAXUS(n=8,146)Bern-Rotterdam2极晚期支架血栓 第一代DES随访4 年累计发生率2009.5.16 医大一院医大一院E

5、ndeavorDriver1.5%0.7%P=0.0710%2%4%6%8%10%0903607201440ARC Def/Prob ST180 270450 540630810900 990 1080 117013501260DaysENDEAVOR Pooled Safety:Mauri,TCT 2019.E I(5 yr),E II(4 yr),E IICA(4 yr),E III(3 yr),E IV(2 yr)&E PK(1 yr).P values are unadjusted for multiple comparisons.Pooled Kaplan-Meier analysi

6、s.2009.5.16 医大一院医大一院0.0%0.5%1.0%1.5%2.0%2.5%3.0%036072010801440ARC(Def/ProbDaysEndeavor 2068 2036 16501087 No.at RiskCypher 863 848 824789 Taxus 1351 1300 11177151 Year2 Years3 YearsPooled DataXience V/Promus 892 865 NA NA4 Years1.Mauri et al.TCT 2019.2.Mauri L et al.N Engl J Med.2019;356:1020-1029.

7、3.Serruys PW et al.ACC 20193.Stone GW et al.PCR 2019.2009.5.16 医大一院医大一院7.0%4.6%ENDEAVOR Pooled Safety:Mauri,TCT 2019.E I(5 yr),E II(4 yr),E IICA(4 yr),E III(3 yr),E IV(2 yr)&E PK(1 yr).P values are unadjusted for multiple comparisons.Pooled Kaplan-Meier analysis.EndeavorDriverP=0.0150%2%4%6%8%10%090

8、3607201440CD/MI180 270450 540630810900 990 1080 117013501260Days2009.5.16 医大一院医大一院%DAPT依从性依从性DaysE I(5 yr),E II(4 yr),E IICA(4 yr),E III(3 yr),E IV(2 yr)&E PK(1 yr).DAPT usage based on case report forms.The optimal duration of dual antiplatelet therapy,specifically clopidogrel,is unknown and DES thr

9、ombosis may still occur despite continued therapy.DAPT protocol required:EI,EII,EII CA,EIII,EPK 3 months Endeavor:EI,EII,EII CA,EPK,EIII,EIV(n=2132)DAPT protocol required:EIV 6 months 置入Endeavor的患者随访1年时只有39%进行双重抗血小板治疗 2009.5.16 医大一院医大一院2009.5.16 医大一院医大一院Histopathology快速的快速的药药物洗脱物洗脱支架支架设计设计=减少减少损伤损伤(

10、圆润纤细圆润纤细的金属的金属丝丝)%Drug ElutedTime(Days)65879899PC 基底层基底层 (1m)药物层药物层90%Zotarolimus10%PC(2-4m)Stent Strut生物相容性的生物相容性的 PC安全的配方安全的配方2009.5.16 医大一院医大一院猪冠脉猪冠脉180 天天BaselineAch(10-5M)mm90days2009.5.16 医大一院医大一院OCT血管血管镜镜EndothelialFunctionProximalDistalIVUSZES(n=14)vs.SES(n=16)8 个月随个月随访访ZES 改善新生内膜覆盖改善新生内膜覆盖(

11、P=0.0004)并并且更少血栓形成且更少血栓形成wata et al;J Am Coll Cardiol 2019;52;789-9017个患者个患者44 个重叠个重叠ZES 6 个月随个月随访访(24,076 个金属个金属丝丝分析分析)ZES 无无贴贴壁不良壁不良,100%内皮覆盖内皮覆盖;无附无附壁血栓壁血栓Guagliumi et al;ESC 2019541 ZES pts 8 个月随个月随访访0.4%晚期晚期贴贴壁不良壁不良;无正性重塑无正性重塑;均匀均匀的新生内膜分布的新生内膜分布Fitzgerald et al;Stanford IVUS core lab ZES(n=20)v

12、s.SES(n=20)vs.BMS(n=10);乙乙酰酰胆碱胆碱试验试验 6 个月个月;ZES较较SES 改善了内皮功改善了内皮功能能(P0.001),和和 BMS结结果相似果相似Kim et al;ACC 2019 2009.5.16 医大一院医大一院2009.5.16 医大一院医大一院9-12MonthsTLR 1year靶病变血运重建1 年以前和1年以后2009.5.16 医大一院医大一院TaxusEndeavorFreedom from TLR100%90%95%0306090120150180210240270300330360Time after Initial Procedure

13、(days)TLR-free 95.5%96.8%0.195EndeavorTaxusP(log rank)ENDEAVOR IV 360天无 TLR生存率2009.5.16 医大一院医大一院Sirius Trial,Holmes et al,Circulation 2019TAXUS IV,Stone et al,Circulation 2019Endeavor II,Fajadet et al.Circulation.2019;114:98-806.2009.5.16 医大一院医大一院4.64.1ENDEAVOR II TAXUS IVSIRIUS3.00.620.390.17ENDEAV

14、OR II TAXUS IVSIRIUS0.360.230.249个月个月TLR(%)晚期晚期丢丢失失(mm)支架内支架内LL(mm)节节段内段内 LL(mm)*12 month analysisData from different clinical trials are not suitable for comparison.SIRIUS.Moses et al.NEJM.2019;349:1315-1323.TAXUS IV.Stone et al.NEJM.2019;350:221-231.SIRIUS diabetes subset.Circulation.2019;109:2273

15、-2278.TAXUS IV diabetes subset.J Am Coll Cardiol.2019;45:1172-1179.Fajadet et al.Circulation.2019;114:98-806.关键试验:晚期丢失 vs.TLR1-2%的差别2009.5.16 医大一院医大一院DES 研究进展 4年TLR 标志性分析Endeavor II(n=581/598)Sirius(n=501/525)Taxus IV(n=618/650)Days%TLR4 Year Clinical Results of TAXUS IV,Stone,ACC 20194 year Outcome

16、s in the Sirius Trial,Leon,TCT 2019Endeavor II 4 year:Fajadet et al.PCR 20192009.5.16 医大一院医大一院9-12月TLR 1年靶病变血运重建TLR1 年以内和1年以后2009.5.16 医大一院医大一院CypherXienceEndeavorDriver28天兔子动脉粥样硬化血管的内皮修复Atherosclerotic rabbit model,representative healing at 28 days.Presented by Renu Virmani,CRT,2019.2009.5.16 医大一院医

17、大一院n/aEndeavor II(n=581/598)Sirius(n=501/525)Taxus IV(n=618/650)5.96.57.27.2R2=0.9524024681012345Years of Follow-upTLR(%)4.96.87.99.46.3R2=0.9762024681012345Years of Follow-upTLR(%)4.45.66.97.89.1R2=0.99730246810Years of Follow-upTLR(%)123454 Year Clinical Results of TAXUS IV,Stone,ACC 20194 year Ou

18、tcomes in the Sirius Trial,Leon,TCT 2019Endeavor II 4 year:Fajadet et al.PCR 20192009.5.16 医大一院医大一院DES 研究进展 随访4 年TLR 标志性研究Endeavor II(n=581/598)Sirius(n=501/525)Taxus IV(n=618/650)Days%TLR4 Year Clinical Results of TAXUS IV,Stone,ACC 20194 year Outcomes in the Sirius Trial,Leon,TCT 2019Endeavor II 4

19、 year:Fajadet et al.PCR 2019 第一代第一代DES在置入在置入1年后年后TLR危险因素持续存在危险因素持续存在2009.5.16 医大一院医大一院1.Mauri et al.TCT 2019.2.Stone,G.et al.N Engl J Med.2019;356:998-10082009.5.16 医大一院医大一院6.7%7.8%310 d940 d10.1%518 d0%5%10%15%20%25%30%0180360540720900108012601440随访天数TLREndeavorCypherTaxusResults come from separate

20、 clinical trials.Data may differ in a head-to-head comparison.1.Mauri et al.TCT.2019.ENDEAVOR Pooled Safety:E I(5 yr),E II(4 yr),E IICA(4 yr),E III(3yr),E IV(2 yr)&E PK(1 yr).2.3.Stone,G.et al.N Engl J Med.2019;356:998-1008.2009.5.16 医大一院医大一院TLR(%)N=322N=7254 yearsEI,EII,EIICA,EIII,EIV,E-PKN=(2132)N

21、=2132Endeavor试验累积数据分析:第 1和 第4 年 随访高危亚组TLR对照 2.5 mmRVD糖尿病糖尿病AllPatients20 mmLesionseFIVE 12 month data:Rothamn et al.PCR 20191 yearN=5552009.5.16 医大一院医大一院3.0%2.5%2.0%1.5%1.0%0.5%0.0%ARC(Def/Prob)1.Mauri et al.TCT 2019.2.Mauri L et al.N Engl J Med.2019;356:1020-1029.3.Serruys PW et al.ACC 2019.3.Stone

22、 GW et al.PCR 2019.%TLR7.0%6.0%5.0%4.0%3.0%2.0%0.0%1.0%TLR Landmark to 4 years036072010801440Days第一代第一代DES在置入在置入1年后年后TLR危险因素持续存在危险因素持续存在导致晚期追赶导致晚期追赶ARC Def/Prob ST Landmark Analysis4 Year Clinical Results of TAXUS IV,Stone,ACC 2019.4 year Outcomes in the Sirius Trial,Leon,TCT 2019.Endeavor II 4 year:Fajadet et al.PCR 2019.2009.5.16 医大一院医大一院2009.5.16 医大一院医大一院