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1、Endeavor Sprint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,Endeavor Sprint,支架输送系统,Endeavor,Endeavor Sprint 在Endeavor基础上改良,Endeavor Sprint 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,*Medtronic crossing profile testing con
2、ducted with 3.5 mm x 18 mm Endeavor Sprint,CYPHER SELECT Plus,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.,小外径设计为挑战性病变的治疗提供便利,Endeavor
3、 Sprint 通过外径和输送性,Endeavor Sprint进一步减小推送杆尺寸:可进行更复杂的器械操作,Endeavor Sprint 最佳输送有效性利于临床挑战更复杂病例,Endeavor Sprint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,1 year,急性1天,晚期 1 个
4、月 1年,亚急性1天-1个月,早期 1个月,晚晚期 1年,早期支架血栓 30天以内,1 个月,1 年,晚期 1 个月 1年,晚期支架血栓 1 年以内,1 个月,1 年,晚晚期 1年,极晚期支架血栓 超过1 年,Wenaweser et al;J Am Coll Cardiol 2008;52:1134-40Mauri et al;N Engl J Med 2007;356:1020-9.,Time since PCI in years,Cumulative Incidence,%,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End
5、eavor: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,ARC Def/Prob ST,180,270,450,540,630,810,900,990,1080,1170,1350,1260,Days,ENDEAVOR Pooled Safety:Mauri,TCT 2008.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
6、 are unadjusted for multiple comparisons.Pooled Kaplan-Meier analysis.,ENDEAVOR 临床研究启示 随访 4 年 ARC 肯定/可能支架血栓率,0.0%,0.5%,1.0%,1.5%,2.0%,2.5%,3.0%,0,360,720,1080,1440,ARC(Def/Prob,Days,Endeavor 2068 2036 16501087,No.at Risk,Cypher 863 848 824789,Taxus 1351 1300 1117715,1 Year,2 Years,3 Years,Pooled Dat
7、a,Xience V/Promus 892 865 NA NA,4 Years,1.Mauri et al.TCT 2008.2.Mauri L et al.N Engl J Med.2007;356:1020-1029.3.Serruys PW et al.ACC 20083.Stone GW et al.PCR 2008.,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%,ENDEAVOR Pooled Safety:Mauri,TCT 2008.E I(5 yr),E II(4 yr),E IICA(4 yr),E III(3 yr),E IV(
8、2 yr)&E PK(1 yr).P values are unadjusted for multiple comparisons.Pooled Kaplan-Meier analysis.,P=0.015,0%,2%,4%,6%,8%,10%,0,90,360,720,1440,CD/MI,180,270,450,540,630,810,900,990,1080,1170,1350,1260,Days,ENDEAVOR 临床研究启示 随访 4 年 Endeavor比 Driver显著性降低了心源性死亡/心梗,%DAPT依从性,Days,E I(5 yr),E II(4 yr),E IICA(
9、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 thrombosis may still occur despite continued therapy.,DAPT protocol required:EI,EII,EII CA,EIII,EPK 3 months,Endeavor:EI,EII,EII
10、 CA,EPK,EIII,EIV(n=2132),DAPT protocol required:EIV 6 months,ENDEAVOR 临床试验DAPT依从性,置入Endeavor的患者随访1年时只有39%进行双重抗血小板治疗,Endeavor 为什么能降低极晚期支架血栓(VLST)发生的风险？,药物洗脱支架长期应用：安全性与疗效,Histopathology,快速的药物洗脱,支架设计=减少损伤(圆润纤细的金属丝),PC 基底层(1m),药物层90%Zotarolimus10%PC(2-4m),Stent Strut,生物相容性的 PC,安全的配方,ENDEAVOR 安全性涉及因素设计特点
11、,%Endotheliazation,内皮覆盖,组织学,猪冠脉180 天,7,90,28,180,Days,Endeavor,eNOS 标记,ENDEAVOR 安全性涉及因素动物模型研究,OCT,血管镜,EndothelialFunction,IVUS,ZES(n=14)vs.SES(n=16)8 个月随访ZES 改善新生内膜覆盖(P=0.0004)并且更少血栓形成wata et al;J Am Coll Cardiol 2008;52;789-90,17个患者44 个重叠ZES 6 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Guagliumi et
12、 al;ESC 2008,541 ZES pts 8 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Fitzgerald et al;Stanford IVUS core lab,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Kim et al;ACC 2008,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,TLR 1year,TLR 1y
13、ear,靶病变血运重建1 年以前和1年以后,Freedom from TLR,100%,90%,95%,0,30,60,90,120,150,180,210,240,270,300,330,360,Time after Initial Procedure(days),ENDEAVOR IV 360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,Sirius Trial,Holmes et al,Circulation 2004TAXUS IV,Stone et al,Circulation 2004Endeavor II,Fajadet et al.Circulation.2
14、006;114:98-806.,4.6,4.1,ENDEAVOR II,TAXUS IV,SIRIUS,3.0,0.62,0.39,0.17,ENDEAVOR II,TAXUS IV,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),*12 month analysisData from different clinical trials are not suitable for comparison.,SIRIUS.Moses et al.NEJM.2003;349:1315-1323.TAXUS IV.Stone e
15、t al.NEJM.2004;350:221-231.SIRIUS diabetes subset.Circulation.2004;109:2273-2278.TAXUS IV diabetes subset.J Am Coll Cardiol.2005;45:1172-1179.Fajadet et al.Circulation.2006;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,Endeavor II(n=581/598),Sirius(n=501/525),Taxus IV(n=618/650),Days,%TLR
16、,4 Year Clinical Results of TAXUS IV,Stone,ACC 20064 year Outcomes in the Sirius Trial,Leon,TCT 2006Endeavor II 4 year:Fajadet et al.PCR 2008,9-12月,TLR 1年,TLR 1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Atherosclerotic rabbit m
17、odel,representative healing at 28 days.Presented by Renu Virmani,CRT,2008.,n/a,Endeavor II(n=581/598),Sirius(n=501/525),Taxus IV(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,Years of Follow-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,Yea
18、rs of Follow-up,TLR(%),4.4,5.6,6.9,7.8,9.1,R,2,=0.9973,0,2,4,6,8,10,Years of Follow-up,TLR(%),1,2,3,4,5,4 Year Clinical Results of TAXUS IV,Stone,ACC 20064 year Outcomes in the Sirius Trial,Leon,TCT 2006Endeavor II 4 year:Fajadet et al.PCR 2008,DES 研究进展 随访4 年TLR 标志性研究,Endeavor II(n=581/598),Sirius(n
19、=501/525),Taxus IV(n=618/650),Days,%TLR,4 Year Clinical Results of TAXUS IV,Stone,ACC 20064 year Outcomes in the Sirius Trial,Leon,TCT 2006Endeavor II 4 year:Fajadet et al.PCR 2008,第一代DES在置入1年后TLR危险因素持续存在,1.Mauri et al.TCT 2008.2.Stone,G.et al.N Engl J Med.2007;356:998-1008,累积DES分析基线形态学,6.7%,7.8%,31
20、0 d,940 d,10.1%,518 d,0%,5%,10%,15%,20%,25%,30%,0,180,360,540,720,900,1080,1260,1440,随访天数,TLR,Endeavor,Cypher,Taxus,Results come from separate clinical trials.Data may differ in a head-to-head comparison.1.Mauri et al.TCT.2008.ENDEAVOR Pooled Safety:E I(5 yr),E II(4 yr),E IICA(4 yr),E III(3yr),E IV(
21、2 yr)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=725,4 years,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,2.5 mmRVD,糖尿病,AllPatients,20 mmLesions,eFIVE 12 month data:Rothamn et al.PCR 2008,1 year,N=555,3.0%,2.5%,2.0%,1.5%,1.0%,0.5%
22、,0.0%,ARC(Def/Prob),DES 研究进展,1.Mauri et al.TCT 2008.2.Mauri L et al.N Engl J Med.2007;356:1020-1029.3.Serruys PW et al.ACC 2008.3.Stone GW et al.PCR 2008.,TLR Landmark to 4 years,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,ARC Def/Prob ST Landmark Analysis,4 Year Clinical Results of TAXUS IV,Stone,ACC 2006.4 year
23、 Outcomes in the Sirius Trial,Leon,TCT 2006.Endeavor II 4 year:Fajadet et al.PCR 2008.,安全性尽管1年后仅39%的Endeavor患者服用双联抗血小板药：随访4年累积支架血栓 ARC（肯定/可能）仅 0.7%vs BMS 1.5%与其它DES相比，1年内支架血栓发生率相似；1年后明显地较其它DES低有效性随访4年近1000名患者，Endeavor TLR较低6.7%与其它DES相比，1年内相似的TLR；1年后几乎没有晚期追赶 多聚物影响长期安全性和有效性Endeavor 生物相容性PC多聚物，带来快速、完全、
24、功能完好的内皮修复。,Endeavor 临床总结,Thank you for your attention！,MajpjMVcyzj21HLfrvy96dv02lPPfYgxUS7IYmZkyEmZ0kGeYZS3bpLCkYH1lt4EK7CxmUX3ijoYSOer7ZuaVWYgz4EpZrUirVpMzzvNtf1XZw5oswSXOtFaejnOcmfE1lZgnN1RSXg8wLCG8CVQ3XPJMvodPFWcpiYJgZazNSEPNIaklYSu7qSd1UpaxmZDlpN9zW7kljfsLCLi26Yv109ffbnDH8LbUN1G6ACURQ39eG12KHL9t
25、XsZ1jzgoCK8g1kuNOh5eFvcmVT5ZYVQt9zk3rp3qLnf02FovEXxVRxjCcFRNppiJljNiOuk6fONnyX7fyGg7sXZ49BmCN5oy9VesHpKzdjTKwjrkCEQCFDehVmGax3lrOEbw63VscA3YSijtUKoCyiLzAlVRp7l4QgPNHxvJFFDyjUVN3oHlMah0XBd4uTbkfPIhHtw0evPmYOrdhEDoPwvYhzlGplU1AU9mpyiCXH8gpPCBRYjq77VcnbXumNE1yGfyTsbSj89J63kRTKDkKUg3mdS5sJ4X5cQ8dK7oW9Ik
26、ScssECQdz2O9UTlpRjAFPChjhLdzopQzwxQf8ozdzOhogwAooXpUF83BX4C3jRgjDJiiXEUDMaNz4vQ4n164vspddHvOIVuBBdMA4xp1YhiHk0vOJ8TL1BxogzVlMpmod6ianYGmksQq6NWCEd56hZF4wfaNyZcrGfNxnPiG6ZAxSkfmhJAKtNmCqbRmppeXp8inz4eq3HkWCMSORyMMX522xpHG6basNr6KQfbZsFbHjzyNlJrruLolKFcC84dqfijBO5Dy2NaBcNEBPgQrT12PgpcKx2or2YChN5DPjs80zzdtdAdTKuW4uVv9bbZu3K2SZ2aEhTlIC1UqrIWibkzwHh6p8gLv26zr01mJybfOzFc4T7kQH1IpPwOzMDnAKPLsLrznXGjFNIA9bSWWms6ibKZwQIKrMzalwbFrQJvOP1rPH8rx2KkyYqrtQk5VRwM1HSX,
