1、药物支架植入后理想的抗血小板时间更长或更短?,罗建方广东省人民医院,内容,临床使用(Dural Antiplatelet Therapy, DAPT)难题XIENCE DAPT中断/停用数据不同DES的安全性表现,临床工作常常面临选择,高出血风险潜在停用DAPT可能再狭窄率高,高再狭窄风险复杂病变 支架内血栓风险增加,Photographs taken by and on file at Abbott Vascular.,BMS?,DES?,随着抗拴力度增强,缺血事件 出血并发症,Thromb Haemost. 2010;103:1128-1135.,不同临床研究中DAPT依从情况,DAPT不
2、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,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,XIENCE: 有证可循的表现,一项又一项的研究,XIENCE:首个CE认证 3个月DAPT(双联抗血小板治疗),Now with3 MonthDAPT,Source: 1. Based on patient numbers from various Abbott and non-Abbott tr
3、ials. Data on file at Abbott Vascular. 2. Trials registered on clinicaltrials.gov as of August 3, 2011.,XIENCE 获得CE批准 3个月DAPT,XIENCE 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),XIENCE V USA,XIENCE V USA无对照注册研究,共入选真实世界患者5054
4、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 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.,Source: Dr. James Hermiller, XIENCE V USA Registry, 1-Year Results, PCR 2010.,AP293
5、2510 Rev. A. Information contained herein for distribution outside the USA only. 2010 Abbott Laboratories,在XIENCE V USA 中,间断或停止DAPT 后ARC定义确诊的/可能的支架血栓发生率 (30 天 1 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%,回顾 2010 PCR,Source: Dr. James Hermiller, XIENCE V USA Registry, 1-Year Results, PCR 2010.
6、,在XIENCE V USA 中,间断或停止DAPT 后ARC定义确诊的/可能的支架血栓发生率 (30 天 1 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%,回顾 2010 PCR,共计13,259名植入Xience患者,SPIRIT IIn=223,SPIRIT IIIn=669,SPIRIT IVn=2458,SPIRIT Vn=2617,SPIRIT Womenn=1514,XIENCE V USAn=4795,XIENCE V Indian=983,11,219 位患者有完整的DAPT 用药记录,2,040 位患者DAPT 用药记录
7、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 -2年,支架血栓大型荟萃分析
8、DAPT中断与支架血栓的发生,回顾 2011 TCT,XIENCE 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%,XIENCE大型荟萃分析 2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=11,219,XIENCE 大型荟萃分析术后两年,XIENCE表现出极低的迟发晚期支架
9、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.,XIENCE大型荟萃分析 2年支架血栓 ( ARC 定义确定的/可能的),XIENCE 大型荟萃分析XIENCE为停用DAPT时低支架血栓发生率设定了新的标准,使用XIENCE,“DAPT中断对99.4%的患者而言不会导致支架血栓。” Dr. Gregg Stone,Source: Stone, G.
10、 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 2年支架血栓与DAPT 停用(ARC定义确定的/可能的),n=11,219,与从未中断相比p=0.34,与从未中断相比p=0.33,1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
11、月时停用,1-2年时停用,回顾 2011 TCT,SPIRIT-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SPIRIT II, SPIRIT III, SPIRIT IV 及COMPARE共6,789名患者,随机入组 XIENCE V vs. Taxus分4个组评估DAPT 1-6个月中断6-12个月中断12-24个月中断从未中断首个DAPT永久停用研究,E.Kedhi SPIRIT-COMPARE Meta DAPT Discontinuation, ACC 2012,XIENCE Vn=4247,Taxusn=2542,2012 ACC,SPIRIT-
12、COMPARE荟萃分析首个DAPT永久停用研究,“随访观察使用Xience治疗的患者至术后两年,发现在术后1个月之后的任何时间永久性停用DAPT对支架血栓的发生率没有造成影响。” PI Kedhi,E.Kedhi SPIRIT-COMPARE Meta DAPT Discontinuation, ACC 2012,p = 0.75,p = 0.05,2012 ACC,DAPT 中断研究-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.
13、PCR 2012.,研究,XIENCE V (n=10,615),研究设计,患者人群,XIENCE V USA,SPIRIT V,SPIRIT WOMEN,XIENCE V INDIA,n=6,516,n=1,662,n=1,506,n=931,多中心,单臂 Open Label,真实世界,真实世界,真实世界,真实世界,2012 PCR,复杂的真实世界患者群 术后两年低支架血栓发生率,支架血栓 ARC 确定的/可能的 (%),0.68%,Pooled data of 10,615 patients from four real-world trialsXIENCE V USA (n=6516)
14、, SPIRIT V (n=1,662), SPIRIT WOMEN SAS (n=1,506) and XIENCE V India (n=931). Source: Palmerini, T., PCR 2012.,月,2012 PCR,XIENCE 术后3个月后中断DAPT支架血栓为0%,首次中断DAPT的时间及支架血栓发生率 随访至12个月,Source: Palmerini T., PCR 2012.,* Including patients with no DAPT Interruption except possibly after Stent Thrombosis though
15、 365 days.,中断DAPT后出现的支架血栓 ARC 确定的/可能的 (%),0.68%,1.64%,0.21%,0.00%,从未中断*,DAPT 中断,0-3 月,3-12 月,2012 PCR,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,XIENCE: 有证可循的表现, 一项又一项的研究,All statements being made and data shown are reflective of the entire patient population in the study and are not representative
16、 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 the XIENCE V
17、 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.,COMPARE研究: 随访3
18、年支架血栓发生率,COMPARE: 支架血栓 3年(ARC 确定的),单中心, 1,800例患者ISS研究,1:1 随机入组 XIENCE (n=897) vs. Taxus Liberte (n=903),Source: Smits, P. Compare 3 Year Results. TCT 2011,p=0.0007 (log-rank test),69%,累计事件发生率,术后时间(天),XIENCE: 与Cypher相比持续的低支架血栓发生率,ARC definite stent thrombosis is confirmed by the presence of an acute
19、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 2010. ST rates are from
20、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 Revasculariz
21、ation. JACC Vol. 57, No. 21, 2011:214351. Investigator Sponsored Study,RESOLUTE All Comers 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,RESOLUTE 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% Endeav
22、or Resolute; p=0.012 年确定的支架血栓发生率 : 0.5% XIENCE; 1.3% Endeavor Resolute; p=0.05,0.71%,1.43%,p=0.10,XIENCE Vn=1,130,Endeavor Resoluten=1,120,3 年确定的支架血栓发生率,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-elu
23、ting coronary stents: 2-year patient-related versus stent-related outcomes from the RESOLUTE All Comers trial. The Lancet. April 9, 2011;377:1241-47.,RESOLUTE 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: Windecker S, PCR 2012.,累积事件发生率,3年 TLF,13.1%,12.4%,8.2%,11.2%,8.3%,10.7%,EXAMINATION 研究-X
24、IENCE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,“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
25、 Investigator, EXAMINATION Trial,p=0.01,0.5%,1.9%,n=751,Sources: 1M. Sabate, EXAMINATION 1-Year Presentation. ESC 2011. 2W. Wijns. EXAMINATION Discussant Presentation. ESC 2011. Investigator Sponsored Study,1年 ARC 定义确定的支架血栓1,n=747,“医生通过使用新型的DES,尤其是这个特定品牌的DES,可以减少在STEMI患者中使用DES时对早期安全性的担忧.” Dr. Willia
26、m Wijns EXAMINATION Discussant, ESC 20112,74%降低,EXAMINATION 研究-XIENCE的安全性优于BMS,Source: M. Sabate, EXAMINATION 1-Year Presentation. ESC 2011. Investigator Sponsored Study,XIENCE V,n=751,MULTI-LINK VISION,n=747,0.9%,2.6%,p=0.01,ARC定义确定的/可能的支架血栓 1年,ARC定义确定的/可能的支架血栓发生率 (%),3.0,2.5,2.0,1.5,1.0,0.5,0,XIEN
27、CE V,急性,亚急性,晚期,MULTI-LINK VISION,急性,亚急性,晚期,The cumulative ST rates are based on Kaplan-Meier estimates.,EXAMINATION 研究-XIENCE的安全性优于BMS,支架血栓网络荟萃分析 XIENCE是市场上最安全的支架,“目前发现CoCrEES (XIENCE)较BMS有更低的支架血栓发生率,如果在将来的研究中得到进一步证实,将会带来治疗模式的巨大转变。”1“有些人认为类似于裸支架的产品应该具有更低的支架血栓发生率,并基于此假设致力于可吸收涂层支架的研发。这个研究带来的发现可能会让这些人停
28、下来。”2,Source: 1Palmerini et al. The Lancet. March 23, 2012 DOI:10.1016/S0140-6736(12)60324-9 2Ormiston. The Lancet, March 23, 2012 DOI:10.1016/S0140-6736(12)60440-1,Source: Palmerini et al. The Lancet. March 23, 2012 DOI:10.1016/S0140-6736(12)60324-9,2602潜在相关的文献,排除2441篇2117篇没有对DES进行比较324篇是对已有研究的事后分析
29、,亚组分析,随访或汇总分析,对161篇文献进行全面审阅,排除112篇84篇文献不是RCT13篇涉及DES没有获得FDA审批11篇研究的支架血栓不是ARC定义4篇是DES汇总分析,共49篇文献满足要求,49个RCT50,844位患者,FDA批准支架BMS,Cypher,Taxus,Endeavor,Resolute, Promus Element, Xience,支架血栓网络荟萃分析 研究设计,1 and 2 Year Definite Stent Thrombosis Rate Pooled Odds Ratio*,Palmerini et al. The Lancet. March 23,
30、2012 DOI:10.1016/S0140-6736(12)60324-9,* An odds ratio is a method of comparing whether the probability of an event is the same between two groups,Xience支架血栓发生率显著低于所有对照产品,支架血栓网络荟萃分析XIENCE是唯一一个术后2年支架血栓发生率低于BMS的DES,Palmerini et al. The Lancet. March 23, 2012 DOI:10.1016/S0140-6736(12)60324-9,与 XIENCE相
31、比支架血栓风险成倍增加一年支架血栓发生率比值比,支架血栓网络荟萃分析 XIENCE是市场上最安全的支架,XIENCE,在真实世界研究中,持续一致的低支架血栓发生率,Source: 1. Smits, PCR 2012. 2.Serruys, PCR 2010. 3.Okkels-Jensen, TCT 2011. 4. Stone, TCT 2010. 5.Windecker, PCR 2012. 6.Raber, ESC 2010. 8.Smits, TCT 2011. Results from clinical trials are not directly comparable. Information provided for educational purposes.,结论,XIENCE支架具有出色的安全性表现,并获得CE批准,最少使用3个月DAPT对于临床工作而言,常规选择具有最佳安全性的DES将为患者带来更好的治疗对于一些具有潜在DAPT停用风险的患者,如决定选用DES应优先考虑具有短DAPT适应症的药物洗脱支架,