美敦力新一代药物洗脱支架的安全性与有效性齐国先

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 conducted 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 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,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;52:1134-40 Mauri 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 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,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 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 1650 1087,No. at Risk,Cypher 863 848 824 789,Taxus 1351 1300 1117 715,1 Year,2 Years,3 Years,Pooled Data,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 2008 3. 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 (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 (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 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% Zotarolimus 10% 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,% 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,Endothelial Function,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 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,9-12 Months,TLR 1year,TLR 1year,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 2004 TAXUS IV, Stone et al, Circulation 2004 Endeavor II, Fajadet et al. Circulation. 2006;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 analysis Data from different clinical trials are not suitable for comparison.,SIRIUS. Moses et al. NEJM. 2003;349:1315-1323. TAXUS IV. Stone et 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. TLR 1-2% 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,4 Year Clinical Results of TAXUS IV, Stone, ACC 2006 4 year Outcomes in the Sirius Trial, Leon, TCT 2006 Endeavor II 4 year : Fajadet et al. PCR 2008,9-12 月,TLR 1年,TLR 1年,靶病变血运重建TLR 1 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 model, 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,Years 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 2006 4 year Outcomes in the Sirius Trial, Leon, TCT 2006 Endeavor 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=501/525),Taxus IV (n=618/650),Days,% TLR,4 Year Clinical Results of TAXUS IV, Stone, ACC 2006 4 year Outcomes in the Sirius Trial, Leon, TCT 2006 Endeavor 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%,310 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 (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-PK N=(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 mm RVD,糖尿病,All Patients,20 mm Lesions,eFIVE 12 month data : Rothamn et al. PCR 2008,1