1、药物支架植入后理想的抗血小板时间药物支架植入后理想的抗血小板时间更长或更短？更长或更短？罗建方罗建方广东省人民医院广东省人民医院Information contained herein is for Europe,Middle East and Africa,and Asia Pacific only,and not intended for physicians from France,Japan or the United States.2012 Abbott.All rights reserved.AP2936456-OUS Rev.B.2内容内容 临床使用临床使用(Dural Anti
2、platelet Therapy,DAPT)(Dural Antiplatelet Therapy,DAPT)难题难题 XIENCE DAPTXIENCE DAPT中断中断/停用数据停用数据 不同不同DESDES的安全性表现的安全性表现Information contained herein is for Europe,Middle East and Africa,and Asia Pacific only,and not intended for physicians from France,Japan or the United States.2012 Abbott.All rights
3、reserved.AP2936456-OUS Rev.B.3临床工作常常面临选择临床工作常常面临选择高出血风险高出血风险潜在停用潜在停用DAPT可能可能再狭窄率高再狭窄率高高再狭窄风险高再狭窄风险复杂病变复杂病变 支架内血栓风险增加支架内血栓风险增加Photographs taken by and on file at Abbott Vascular.BMS?DES?Information contained herein is for Europe,Middle East and Africa,and Asia Pacific only,and not intended for physic
4、ians from France,Japan or the United States.2012 Abbott.All rights reserved.AP2936456-OUS Rev.B.4随着抗拴力度增强，缺血事件随着抗拴力度增强，缺血事件 出血并发症出血并发症Thromb Haemost.2010;103:1128-1135.Information contained herein is for Europe,Middle East and Africa,and Asia Pacific only,and not intended for physicians from France,
5、Japan or the United States.2012 Abbott.All rights reserved.AP2936456-OUS Rev.B.5不同临床研究中不同临床研究中DAPTDAPT依从情况依从情况Resolute AC双双联联抗血小板治抗血小板治疗疗XIENCE VEndeavor Resolute1年年83.5%84.4%3年年13.4%13.8%SPIRIT-COMPARE双双联联抗血小板治抗血小板治疗疗XIENCE VTaxus1年年78.3%77.0%2年年50.0%44.5%COMPARE双双联联抗血小板治抗血小板治疗疗XIENCE VPromus Eleme
6、nt1年年70%70%2年年11.4%15.2%PLATINUM双双联联抗血小板治抗血小板治疗疗XIENCE VPromus Element1年年80.5%83.4%2年年48%51.4%Information contained herein is for Europe,Middle East and Africa,and Asia Pacific only,and not intended for physicians from France,Japan or the United States.2012 Abbott.All rights reserved.AP2936456-OUS R
7、ev.B.6DAPTDAPT不依从的临床分析不依从的临床分析 临床常见原因 出血：胃肠道出血，脑血管病等 计划外手术：拔牙，肿瘤，外伤，结石（胆囊、肾脏etc），前列腺肥大等 其他疾病：痛风 DAPT过敏 肾功能不全、肝功能不全 经济因素 带来的后果 支架血栓、心梗、死亡支架血栓、心梗、死亡Information contained herein is for Europe,Middle East and Africa,and Asia Pacific only,and not intended for physicians from France,Japan or the United St
8、ates.2012 Abbott.All rights reserved.AP2936456-OUS Rev.B.7内容 临床使用DAPT的难题 XIENCE DAPT中断/停用数据 不同DES的安全性表现Information contained herein is for Europe,Middle East and Africa,and Asia Pacific only,and not intended for physicians from France,Japan or the United States.2012 Abbott.All rights reserved.AP2936
9、456-OUS Rev.B.8XIENCE:XIENCE:有证可循的表现，一项又一项的研究有证可循的表现，一项又一项的研究XIENCE:首个首个CE认证认证 3个月个月DAPT（双（双联联抗血小板治抗血小板治疗疗）Source:1.Based on patient numbers from various Abbott and non-Abbott trials.Data on file at Abbott Vascular.2.Trials registered on clinicaltrials.gov as of August 3,2011.Information contained h
10、erein is for Europe,Middle East and Africa,and Asia Pacific only,and not intended for physicians from France,Japan or the United States.2012 Abbott.All rights reserved.AP2936456-OUS Rev.B.9XIENCE XIENCE 获得获得CECE批准批准 3 3个月个月DAPTDAPTInformation contained herein is for Europe,Middle East and Africa,and
11、 Asia Pacific only,and not intended for physicians from France,Japan or the United States.2012 Abbott.All rights reserved.AP2936456-OUS Rev.B.10XIENCE CE批准 3个月DAPT大量支持数据 XIENCE V USA（2010 PCR）支架血栓大型荟萃分析（2011 TCT）SPIRIT-COMPARE永久性DAPT停用荟萃分析（2012 ACC）真实世界DAPT中断研究（2012 PCR）Information contained herein
12、is for Europe,Middle East and Africa,and Asia Pacific only,and not intended for physicians from France,Japan or the United States.2012 Abbott.All rights reserved.AP2936456-OUS Rev.B.11XIENCE V USAXIENCE V USA 无对照注册研究，共入选真实世界患者5054名 主要终点为1年期ARC定义的确诊的/可能的支架血栓发生率 标准风险队列是 XIENCE V USA 的一个亚组，患者特征与 SPIRIT
13、 III&IV 相似,不包括以下情况:Source:Patrick Serruys,RESOLUTE AC 1-Year Results,PCR 2010.Source:James Hermiller,XIENCE V USA 1-Year Results,PCR 2010.Information contained herein is for Europe,Middle East and Africa,and Asia Pacific only,and not intended for physicians from France,Japan or the United States.201
14、2 Abbott.All rights reserved.AP2936456-OUS Rev.B.12Source:Dr.James Hermiller,XIENCE V USA Registry,1-Year Results,PCR 2010.AP2932510 Rev.A.Information contained herein for distribution outside the USA only.2010 Abbott Laboratories在在XIENCE V USA 中，间断或停止中，间断或停止DAPT 后后ARC定义确诊的定义确诊的/可能的可能的支架血栓发生率支架血栓发生率
15、 (30 天天 1 年年)XIENCE V USA在真实世界患者群中，6个月后间断或停止DAPT，支架血栓发生率为0%回回顾顾 2010 PCRInformation contained herein is for Europe,Middle East and Africa,and Asia Pacific only,and not intended for physicians from France,Japan or the United States.2012 Abbott.All rights reserved.AP2936456-OUS Rev.B.13Source:Dr.James
16、 Hermiller,XIENCE V USA Registry,1-Year Results,PCR 2010.在在XIENCE V USA 中，间断或停止中，间断或停止DAPT 后后ARC定义确诊的定义确诊的/可能的可能的支架血栓发生率支架血栓发生率 (30 天天 1 年年)XIENCE V USA在标准风险患者群中，30天后间断或停止DAPT，支架血栓发生率为0%回回顾顾 2010 PCRInformation contained herein is for Europe,Middle East and Africa,and Asia Pacific only,and not inten
17、ded for physicians from France,Japan or the United States.2012 Abbott.All rights reserved.AP2936456-OUS Rev.B.14共计共计13,259名植入名植入Xience患者患者SPIRIT IIn=223SPIRIT IIIn=669SPIRIT IVn=2458SPIRIT Vn=2617SPIRIT Womenn=1514XIENCE V USAn=4795XIENCE V Indian=98311,219 位患者有完整的位患者有完整的DAPT 用药记录用药记录2,040 位患者位患者DAP
18、T 用药记录不完整用药记录不完整根据已有的研究，在植入第一代DES的患者中提前停用DAPT与支架血栓相关，因此现有的指南强烈建议接受DES植入的患者需要进行至少1年的DAPT根据这一研究分析，DAPT停用定义为术后2年的随访时间内，任何原因造成的阿司匹林和/或氯比格雷停用至少1天。Source:G Stone.Stent Thrombosis and DAPT Interruption:Insights from the XIENCE V Everolimus Eluting Coronary Stent System Trials.TCT 2011.XIENCE大型荟萃分析大型荟萃分析-2年
19、年支架血栓大型荟萃分析DAPT中断与支架血栓的发生回回顾顾 2011 TCTInformation contained herein is for Europe,Middle East and Africa,and Asia Pacific only,and not intended for physicians from France,Japan or the United States.2012 Abbott.All rights reserved.AP2936456-OUS Rev.B.15XIENCE 大型荟萃分析在超过11,000患者中,XIENCE支架血栓发生率仅为0.75%XIE
20、NCE大型荟萃分析大型荟萃分析 2年支架血栓年支架血栓(ARC 定义确定的/可能的）Source:Stone,G.Stent Thrombosis and DAPT Interruption:Insights from the XIENCEV Everolimus Eluting Coronary Stent System Trials.TCT 2011.n=11,219Information contained herein is for Europe,Middle East and Africa,and Asia Pacific only,and not intended for phys
21、icians from France,Japan or the United States.2012 Abbott.All rights reserved.AP2936456-OUS Rev.B.16XIENCE 大型荟萃分析术后两年，XIENCE表现出极低的迟发晚期支架血栓发生率Source:Stone,G.Stent Thrombosis and DAPT Interruption:Insights from the XIENCEV Everolimus Eluting Coronary Stent System Trials.TCT 2011.n=11,219Stent Thrombos
22、is(%)MonthsXIENCE大型荟萃分析大型荟萃分析 2年支架血栓年支架血栓(ARC 定义确定的/可能的）Information contained herein is for Europe,Middle East and Africa,and Asia Pacific only,and not intended for physicians from France,Japan or the United States.2012 Abbott.All rights reserved.AP2936456-OUS Rev.B.17XIENCE 大型荟萃分析XIENCE为停用DAPT时低支架血
23、栓发生率设定了新的标准使用使用XIENCE，“DAPT中断对中断对99.4%的患者而言不会导致支架血栓。的患者而言不会导致支架血栓。”Dr.Gregg StoneSource:Stone,G.Stent Thrombosis and DAPT Interruption:Insights from the XIENCEV Everolimus Eluting Coronary Stent System Trials.TCT 2011.0.63%0.88%0.44%XIENCE大型荟萃分析大型荟萃分析 2年支架血栓与年支架血栓与DAPT 停用停用(ARC定义确定的/可能的）n=11,219与从未中
24、断相比与从未中断相比p=0.34 与从未中断相比与从未中断相比p=0.331个月或1个月以内停用,2.55%;1-3个月停用,2.11%;3-6个月停用,1.38%,p=0.13 vs.从未停用从未停用6-12个月时停用1-2年时停用回回顾顾 2011 TCTInformation contained herein is for Europe,Middle East and Africa,and Asia Pacific only,and not intended for physicians from France,Japan or the United States.2012 Abbott
25、.All rights reserved.AP2936456-OUS Rev.B.18SPIRIT-COMPARE荟萃分析支架血栓和DAPT永久停用 研究者独立进行的荟萃分析，包括研究者独立进行的荟萃分析，包括SPIRIT II,SPIRIT III,SPIRIT SPIRIT II,SPIRIT III,SPIRIT IV IV 及及COMPARECOMPARE 共共6,7896,789名患者，随机入组名患者，随机入组 XIENCE XIENCE V vs.TaxusV vs.Taxus 分分4 4个组评估个组评估DAPT DAPT 1-61-6个月中断个月中断6-126-12个月中断个月中
26、断12-2412-24个月中断个月中断从未中断从未中断 首个首个DAPTDAPT永久停用研究永久停用研究E.Kedhi SPIRIT-COMPARE Meta DAPT Discontinuation,ACC 2012Patients on Dual Antiplatelet TherapyXIENCE VTaxusAt 1 Year78.3%77.0%At 2 Years50.0%44.5%汇总数据库汇总数据库n=6789n=6789n=4247XIENCE Vn=4247Taxusn=25422012 ACCInformation contained herein is for Europ
27、e,Middle East and Africa,and Asia Pacific only,and not intended for physicians from France,Japan or the United States.2012 Abbott.All rights reserved.AP2936456-OUS Rev.B.19SPIRIT-COMPARE荟萃分析首个DAPT永久停用研究 “随访观察使用随访观察使用XienceXience治疗的患者至术后两年，发现在术后治疗的患者至术后两年，发现在术后1 1个月之后的个月之后的任何时间永久性停用任何时间永久性停用DAPTDAPT对
28、支架血栓的发生率没有造成影响。对支架血栓的发生率没有造成影响。”PI KedhiE.Kedhi SPIRIT-COMPARE Meta DAPT Discontinuation,ACC 2012p=0.75p=0.052012 ACCInformation contained herein is for Europe,Middle East and Africa,and Asia Pacific only,and not intended for physicians from France,Japan or the United States.2012 Abbott.All rights r
29、eserved.AP2936456-OUS Rev.B.20DAPT DAPT 中断研究中断研究-真实世界人群真实世界人群汇总分析来自4个真实世界研究的10,615名患者数据919 名患者在3-12个月之间中断DAPT使用“DAPT 中断”包括暂时及永久停用DAPT的患者Source:Palmerini,T.PCR 2012.研究XIENCE V(n=10,615)研究设计患者人群XIENCE V USASPIRIT VSPIRIT WOMENXIENCE V INDIAn=6,516n=1,662n=1,506n=931多中心，单臂 Open Label真实世界真实世界真实世界真实世界201
30、2 PCRInformation contained herein is for Europe,Middle East and Africa,and Asia Pacific only,and not intended for physicians from France,Japan or the United States.2012 Abbott.All rights reserved.AP2936456-OUS Rev.B.21复杂的真实世界患者群复杂的真实世界患者群 术后两年低支架血栓发生率术后两年低支架血栓发生率支架血栓支架血栓 ARC 确定的确定的/可能的可能的(%)0.68%Poo
31、led data of 10,615 patients from four real-world trialsXIENCE V USA(n=6516),SPIRIT V(n=1,662),SPIRIT WOMEN SAS(n=1,506)and XIENCE V India(n=931).Source:Palmerini,T.,PCR 2012.月月真实世界人群(n=10,615)AMI 再狭窄 ACS左主干 分叉病变 糖尿病桥血管 开口病变 EF30%CTO 多支病变 直接支架肾功能不全 多支血管治疗2012 PCRInformation contained herein is for Eu
32、rope,Middle East and Africa,and Asia Pacific only,and not intended for physicians from France,Japan or the United States.2012 Abbott.All rights reserved.AP2936456-OUS Rev.B.22XIENCE 术后3个月后中断DAPT支架血栓为0%首次中断首次中断DAPT的的时间时间及支架血栓及支架血栓发发生率生率 随随访访至至12个月个月Source:Palmerini T.,PCR 2012.*Including patients wit
33、h no DAPT Interruption except possibly after Stent Thrombosis though 365 days.中断中断DAPT后出后出现现的支架血栓的支架血栓 ARC 确定的确定的/可能的可能的(%)0.68%1.64%0.21%0.00%从未中断从未中断*DAPT 中断中断0-3 月月3-12 月月2012 PCRInformation contained herein is for Europe,Middle East and Africa,and Asia Pacific only,and not intended for physician
34、s from France,Japan or the United States.2012 Abbott.All rights reserved.AP2936456-OUS Rev.B.23内容 临床使用DAPT的难题 XIENCE DAPT中断/停用数据 不同不同DESDES的安全性表现的安全性表现Information contained herein is for Europe,Middle East and Africa,and Asia Pacific only,and not intended for physicians from France,Japan or the Unit
35、ed States.2012 Abbott.All rights reserved.AP2936456-OUS Rev.B.24XIENCE:有证可循的表现,一项又一项的研究复杂病变患者的数据包括复杂病变患者的数据包括:左主干左主干AMIAMIACSACS分叉病变分叉病变肾功能不全肾功能不全多支病变多支病变糖尿病糖尿病CTOsCTOs桥血管桥血管再狭窄病变再狭窄病变开口病变开口病变All statements being made and data shown are reflective of the entire patient population in the study and ar
36、e not representative of any specific lesion type.S Silber et al.Unrestricted randomized use of two new generation drug-eluting coronary stents:2-year patient-related versus stent-related outcomes from the RESOLUTE All Comers trial.The Lancet.April 9,2011;377:1241-47;M Krucoff.One-Year Results from t
37、he XIENCE V USA Condition of Approval Study,TCT 2010.1.Based on patient numbers from various Abbott and non-Abbott-sponsored trials.Data on file at Abbott Vascular.2.Data from SPIRIT FIRST,SPIRIT II and SPIRIT III trials.3.Trials registered on www.clinicaltrials.gov as of Aug.3,2011.Information cont
38、ained herein is for Europe,Middle East and Africa,and Asia Pacific only,and not intended for physicians from France,Japan or the United States.2012 Abbott.All rights reserved.AP2936456-OUS Rev.B.25 COMPARE研究:随访3 年支架血栓发生率COMPARE:支架血栓支架血栓 3年年(ARC 确定的)单中心单中心,1,800例患者例患者ISS研究，研究，1:1 随机入组随机入组 XIENCE(n=89
39、7)vs.Taxus Liberte(n=903)Source:Smits,P.Compare 3 Year Results.TCT 2011p=0.0007(log-rank test)69%累计事件发生率术后时间（天）Information contained herein is for Europe,Middle East and Africa,and Asia Pacific only,and not intended for physicians from France,Japan or the United States.2012 Abbott.All rights reserve
40、d.AP2936456-OUS Rev.B.26XIENCE:与Cypher相比持续的低支架血栓发生率XIENCE Vn=1390Cyphern=1384XIENCE Vn=1597Cyphern=1600XIENCE Vn=652Cyphern=652XIENCE Vn=1342Cyphern=1342p=0.05plog-rank=0.77p=0.17p=0.010%SORT-OUT IV1 9 monthsISAR-TEST 43 2 year LESSON 14 3 year RESET2 1 yearARC definite stent thrombosis is confirmed
41、 by the presence of an acute coronary syndrome with angiographic or autopsy evidence of thrombus or occlusion.Results from different clinical trials are not directly comparable.Information provided for educational purposes only.Sources:1L.Okkels Jensen,SORT OUT IV 9-Month Results Presentation.TCT 20
42、10.ST rates are from Kaplan-Meier estimates.2T.Kimura,RESET 1-Year Results Presentation.ESC 2011.ST rates are from Kaplan-Meier estimates.3R.Byrne.ISAR Test 4 2-Year Results Presentation.TCT 2010.4L.Raber,et al.Long-Term Comparison of Everolimus-Eluting and Sirolimus-Eluting Stents for Coronary Reva
43、scularization.JACC Vol.57,No.21,2011:214351.Investigator Sponsored StudyInformation contained herein is for Europe,Middle East and Africa,and Asia Pacific only,and not intended for physicians from France,Japan or the United States.2012 Abbott.All rights reserved.AP2936456-OUS Rev.B.27RESOLUTE All Co
44、mers 研究3年结果 由美敦力资助的独立的无筛选患者研究 2,292 名患者 1:1 入组XIENCE V及 Resolute 比较 XIENCE 与 Resolute最大的RCT研究Source:Windecker S,PCR 2012双双联联抗血小板治抗血小板治疗疗XIENCE VEndeavor Resolute1年年83.5%84.4%3年年13.4%13.8%Information contained herein is for Europe,Middle East and Africa,and Asia Pacific only,and not intended for phys
45、icians from France,Japan or the United States.2012 Abbott.All rights reserved.AP2936456-OUS Rev.B.28RESOLUTE All Comers 3年结果XIENCE 术后3年的支架血栓是Resolute的一半1 年确定的支架血栓发生率:0.3%XIENCE;1.2%Endeavor Resolute;p=0.012 年确定的支架血栓发生率:0.5%XIENCE;1.3%Endeavor Resolute;p=0.050.71%1.43%p=0.10XIENCE Vn=1,130Endeavor Re
46、soluten=1,1203 年确定的支架血栓年确定的支架血栓发发生率生率支架血栓支架血栓(%)Source:3 year data:Windecker S,PCR 2012,1 and 2 year data:Silber S,et al.Unrestricted randomized use of two new generation drug-eluting coronary stents:2-year patient-related versus stent-related outcomes from the RESOLUTE All Comers trial.The Lancet.A
47、pril 9,2011;377:1241-47.Information contained herein is for Europe,Middle East and Africa,and Asia Pacific only,and not intended for physicians from France,Japan or the United States.2012 Abbott.All rights reserved.AP2936456-OUS Rev.B.29RESOLUTE All Comers 3年结果在几乎所有的临床终点上，XIENCE均体现出了数值上的优势Source:Win
48、decker S,PCR 2012.累累积积事件事件发发生率生率3年年 TLFXIENCE V(n=1,152)Endeavor Resolute(n=1,140)Plog rank=0.65Time After Initial Procedure(months)13.1%12.4%8.2%11.2%8.3%10.7%Information contained herein is for Europe,Middle East and Africa,and Asia Pacific only,and not intended for physicians from France,Japan or
49、 the United States.2012 Abbott.All rights reserved.AP2936456-OUS Rev.B.30EXAMINATION 研究-XIENCE的安全性优于BMS由研究者独立进行的随机研究，1,498名STEMI患者，1:1随机入组XIENCE V 及 MULTI-LINK VISION主要终点:ARC 定义患者导向的1年复合终点，包括全因死亡，全因心梗，全部血运重建1年随访率98%Source:M.Sabate,EXAMINATION 1-Year Presentation.ESC 2011.Investigator Sponsored Study
50、患者导向复合终点患者导向复合终点XIENCE V12.0%MULTI-LINK VISION14.4%p-值0.16支架相关终点支架相关终点终点TLRTVRXIENCE V2.2%3.9%MULTI-LINK VISION5.1%7.0%p-值0.0030.007无筛选STEMI患者 n=1,498XIENCE Vn=741MULTI-LINK VISIONn=747“在临床表现上，Xience V支架显著降低TVR和TLR的发生率，以及确定的/可能的支架血栓发生率.”-Dr.Manel SabatePrincipal Investigator,EXAMINATION TrialInforma
