藥物支架植入后理想的抗血小板時(shí)間更長或更短

1、藥物支架植入后理想的抗血小板時(shí)間—更長或更短？,羅建方廣東省人民醫(yī)院,內(nèi)容,臨床使用(Dural Antiplatelet Therapy, DAPT)難題XIENCE DAPT中斷/停用數(shù)據(jù)不同DES的安全性表現(xiàn),臨床工作常常面臨選擇,高出血風(fēng)險(xiǎn)潛在停用DAPT可能再狹窄率高,高再狹窄風(fēng)險(xiǎn)復(fù)雜病變 支架內(nèi)血栓風(fēng)險(xiǎn)增加,Photographs taken by and on file at Abbott Vascul

2、ar.,BMS?,DES?,,隨著抗拴力度增強(qiáng)，缺血事件↓ 出血并發(fā)癥↑,Thromb Haemost. 2010;103:1128-1135.,不同臨床研究中DAPT依從情況,DAPT不依從的臨床分析,臨床常見原因出血：胃腸道出血，腦血管病等計(jì)劃外手術(shù)：拔牙，腫瘤，外傷，結(jié)石（膽囊、腎臟etc），前列腺肥大等其他疾?。和达L(fēng)DAPT過敏腎功能不全、肝功能不全經(jīng)濟(jì)因素

3、帶來的后果支架血栓、心梗、死亡,內(nèi)容,臨床使用DAPT的難題XIENCE DAPT中斷/停用數(shù)據(jù)不同DES的安全性表現(xiàn),XIENCE: 有證可循的表現(xiàn)，一項(xiàng)又一項(xiàng)的研究,XIENCE:首個(gè)CE認(rèn)證 3個(gè)月DAPT（雙聯(lián)抗血小板治療）,Now with3 – MonthDAPT,Source: 1. Based on patient numbers from various Abbott and non-Abbott tri

4、als. Data on file at Abbott Vascular. 2. Trials registered on clinicaltrials.gov as of August 3, 2011.,XIENCE 獲得CE批準(zhǔn) 3個(gè)月DAPT,XIENCE CE批準(zhǔn) 3個(gè)月DAPT大量支持?jǐn)?shù)據(jù),XIENCE V USA（2010 PCR）支架血栓大型薈萃分析（2011 TCT）SPIRIT-COMPARE永久性DAPT停用薈

5、萃分析（2012 ACC）真實(shí)世界DAPT中斷研究（2012 PCR）,XIENCE V USA,XIENCE V USA無對照注冊研究，共入選真實(shí)世界患者5054名主要終點(diǎn)為1年期ARC定義的確診的/可能的支架血栓發(fā)生率標(biāo)準(zhǔn)風(fēng)險(xiǎn)隊(duì)列是 XIENCE V USA 的一個(gè)亞組，患者特征與 SPIRIT III & IV 相似, 不包括以下情況:,,Source: Patrick Serruys, RESOLUTE AC

6、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.,AP2932510 Rev. A. Information contained herein for

7、 distribution outside the USA only. © 2010 Abbott Laboratories,在XIENCE V USA 中，間斷或停止DAPT 后ARC定義確診的/可能的支架血栓發(fā)生率 (30 天 – 1 年),XIENCE V USA在真實(shí)世界患者群中，6個(gè)月后間斷或停止DAPT，支架血栓發(fā)生率為0%,回顧 2010 PCR,Source: Dr. James Hermiller, X

8、IENCE V USA Registry, 1-Year Results, PCR 2010.,在XIENCE V USA 中，間斷或停止DAPT 后ARC定義確診的/可能的支架血栓發(fā)生率 (30 天 – 1 年),XIENCE V USA在標(biāo)準(zhǔn)風(fēng)險(xiǎn)患者群中，30天后間斷或停止DAPT，支架血栓發(fā)生率為0%,回顧 2010 PCR,共計(jì)13,259名植入Xience患者,SPIRIT IIn=223,SPIRIT IIIn=6

9、69,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 用藥記錄,2,040 位患者DAPT 用藥記錄不完整,,根據(jù)已有的研究，在植入第一代DES的患者中提前停用DAPT與支架血栓相關(guān)，因此現(xiàn)有的指南強(qiáng)烈建議接受DES植入的患者需要進(jìn)行至少1年

10、的DAPT根據(jù)這一研究分析，DAPT停用定義為術(shù)后2年的隨訪時(shí)間內(nèi)，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大型薈萃分析 -

11、2年,支架血栓大型薈萃分析DAPT中斷與支架血栓的發(fā)生,回顧 2011 TCT,XIENCE 大型薈萃分析在超過11,000患者中, XIENCE支架血栓發(fā)生率僅為0.75%,XIENCE大型薈萃分析 2年支架血栓 ( ARC 定義確定的/可能的）,Source: Stone, G. Stent Thrombosis and DAPT Interruption: Insights from the XIENCEV Everol

12、imus Eluting Coronary Stent System Trials. TCT 2011.,,n=11,219,XIENCE 大型薈萃分析術(shù)后兩年，XIENCE表現(xiàn)出極低的遲發(fā)晚期支架血栓發(fā)生率,Source: Stone, G. Stent Thrombosis and DAPT Interruption: Insights from the XIENCEV Everolimus Eluting Coronary

13、Stent System Trials. TCT 2011.,XIENCE大型薈萃分析 2年支架血栓 ( ARC 定義確定的/可能的）,XIENCE 大型薈萃分析XIENCE為停用DAPT時(shí)低支架血栓發(fā)生率設(shè)定了新的標(biāo)準(zhǔn),使用XIENCE，“DAPT中斷對99.4%的患者而言不會導(dǎo)致支架血栓?！报C Dr. Gregg Stone,Source: Stone, G. Stent Thrombosis and D

14、APT Interruption: Insights from the XIENCEV Everolimus Eluting Coronary Stent System Trials. TCT 2011.,0.63%,0.88%,0.44%,XIENCE大型薈萃分析 2年支架血栓與DAPT 停用(ARC定義確定的/可能的）,n=11,219,與從未中斷相比p=0.34,與從未中斷相比p=0.33,1個(gè)月或1個(gè)月以內(nèi)停用, 2.5

15、5%; 1-3個(gè)月停用, 2.11%;3-6個(gè)月停用, 1.38%, p=0.13 vs. 從未停用,從未停用,6-12個(gè)月時(shí)停用,1-2年時(shí)停用,回顧 2011 TCT,SPIRIT-COMPARE薈萃分析支架血栓和DAPT永久停用,研究者獨(dú)立進(jìn)行的薈萃分析，包括SPIRIT II, SPIRIT III, SPIRIT IV 及COMPARE共6,789名患者，隨機(jī)入組 XIENCE V vs. Taxus分4個(gè)組評估DAP

16、T 1-6個(gè)月中斷6-12個(gè)月中斷12-24個(gè)月中斷從未中斷首個(gè)DAPT永久停用研究,E.Kedhi SPIRIT-COMPARE Meta DAPT Discontinuation, ACC 2012,XIENCE Vn=4247,Taxusn=2542,2012 ACC,SPIRIT-COMPARE薈萃分析首個(gè)DAPT永久停用研究,“隨訪觀察使用Xience治療的患者至術(shù)后兩年，發(fā)現(xiàn)在術(shù)后1個(gè)月之后的任何時(shí)間永久性停

17、用DAPT對支架血栓的發(fā)生率沒有造成影響?！?PI Kedhi,E.Kedhi SPIRIT-COMPARE Meta DAPT Discontinuation, ACC 2012,p = 0.75,p = 0.05,2012 ACC,DAPT 中斷研究-真實(shí)世界人群,匯總分析來自4個(gè)真實(shí)世界研究的10,615名患者數(shù)據(jù)919 名患者在3-12個(gè)月之間中斷DAPT使用“DAPT 中斷”包括暫時(shí)及永久停用DAPT的患者

18、,Source: Palmerini, T. PCR 2012.,研究,XIENCE V (n=10,615),研究設(shè)計(jì),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，單臂 Open Label,真實(shí)世界,真實(shí)世界,真實(shí)世界,真實(shí)世界,2012 PCR,復(fù)雜的真實(shí)世界患者群 術(shù)后兩年低支架血栓發(fā)生

19、率,支架血栓 ARC 確定的/可能的 (%),0.68%,Pooled data of 10,615 patients from four real-world trials—XIENCE 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.,

20、月,2012 PCR,XIENCE 術(shù)后3個(gè)月后中斷DAPT支架血栓為0%,首次中斷DAPT的時(shí)間及支架血栓發(fā)生率 隨訪至12個(gè)月,,Source: Palmerini T., PCR 2012.,* Including patients with no DAPT Interruption except possibly after Stent Thrombosis though 365 days.,中斷DAPT后出現(xiàn)的支架血栓

21、ARC 確定的/可能的 (%),0.68%,1.64%,0.21%,0.00%,從未中斷*,DAPT 中斷,0-3 月,3-12 月,2012 PCR,內(nèi)容,臨床使用DAPT的難題XIENCE DAPT中斷/停用數(shù)據(jù)不同DES的安全性表現(xiàn),XIENCE: 有證可循的表現(xiàn), 一項(xiàng)又一項(xiàng)的研究,All statements being made and data shown are reflective of the entire p

22、atient population in the study and are 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-

23、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 USA Condition of Approval Study, TCT 2010. 1. Based on patient numbers from var

24、ious 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: 隨訪

25、3 年支架血栓發(fā)生率,COMPARE: 支架血栓 – 3年(ARC 確定的),單中心, 1,800例患者ISS研究，1:1 隨機(jī)入組 XIENCE (n=897) vs. Taxus Liberte (n=903),Source: Smits, P. Compare 3 Year Results. TCT 2011,p=0.0007 (log-rank test),,69%,累計(jì)事件發(fā)生率,術(shù)后時(shí)間（天）,XIENCE: 與Cy

26、pher相比持續(xù)的低支架血栓發(fā)生率,ARC definite stent thrombosis is confirmed by the presence of an acute coronary syndrome with angiographic or autopsy evidence of thrombus or occlusion. Results from different clinical trials are not di

27、rectly comparable. Information provided for educational purposes only. Sources: 1L. Okkels Jensen, SORT OUT IV 9-Month Results Presentation. TCT 2010. ST rates are from Kaplan-Meier estimates. 2T. Kimura, RESET 1-Year R

28、esults 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-Elut

29、ing Stents for Coronary Revascularization." JACC Vol. 57, No. 21, 2011:2143–51. Investigator Sponsored Study,RESOLUTE All Comers 研究3年結(jié)果,由美敦力資助的獨(dú)立的無篩選患者研究2,292 名患者 1:1 入組XIENCE V及 Resolute比較 XIENCE 與 Resolute最大的RCT

30、研究,Source: Windecker S, PCR 2012,RESOLUTE All Comers 3年結(jié)果XIENCE 術(shù)后3年的支架血栓是Resolute的一半,1 年確定的支架血栓發(fā)生率: 0.3% XIENCE; 1.2% Endeavor Resolute; p=0.012 年確定的支架血栓發(fā)生率 : 0.5% XIENCE; 1.3% Endeavor Resolute; p=0.05,0.71%,1.43%,

31、p=0.10,XIENCE Vn=1,130,Endeavor Resoluten=1,120,3 年確定的支架血栓發(fā)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-eluting cor

32、onary 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年結(jié)果在幾乎所有的臨床終點(diǎn)上，XIENCE均體現(xiàn)出了數(shù)值上的優(yōu)勢,Source: Windecker S, P

33、CR 2012.,累積事件發(fā)生率,3年 TLF,13.1%,12.4%,8.2%,11.2%,8.3%,10.7%,,EXAMINATION 研究-XIENCE的安全性優(yōu)于BMS,由研究者獨(dú)立進(jìn)行的隨機(jī)研究，1,498名STEMI患者， 1:1隨機(jī)入組XIENCE V 及 MULTI-LINK VISION主要終點(diǎn): ARC 定義患者導(dǎo)向的1年復(fù)合終點(diǎn)，包括全因死亡，全因心梗，全部血運(yùn)重建1年隨訪率98%,Source: M. Sa

34、bate, EXAMINATION 1-Year Presentation. ESC 2011. Investigator Sponsored Study,“在臨床表現(xiàn)上，Xience V支架顯著降低TVR和TLR的發(fā)生率，以及確定的/可能的支架血栓發(fā)生率.”- Dr. Manel SabatePrincipal Investigator, EXAMINATION Trial,,p=0.01,0.5%,1.9%,n=751,Sou

35、rces: 1M. Sabate, EXAMINATION 1-Year Presentation. ESC 2011. 2W. Wijns. EXAMINATION Discussant Presentation. ESC 2011. Investigator Sponsored Study,1年 ARC 定義確定的支架血栓1,n=747,“醫(yī)生通過使用新型的DES，尤其是這個(gè)特定品牌的DES，可以減少在STEMI患者中使用DES時(shí)對

36、早期安全性的擔(dān)憂.” – Dr. William Wijns EXAMINATION Discussant, ESC 20112,74%降低,EXAMINATION 研究-XIENCE的安全性優(yōu)于BMS,Source: M. Sabate, EXAMINATION 1-Year Presentation. ESC 2011. Investigator Sponsored Study,,,,,,,,XIENCE V,n=751,MU

37、LTI-LINK VISION,n=747,0.9%,2.6%,p=0.01,ARC定義確定的/可能的支架血栓 1年,ARC定義確定的/可能的支架血栓發(fā)生率 (%),3.0,2.5,2.0,1.5,1.0,0.5,0,,,,,,,,XIENCE V,急性,亞急性,晚期,,,,MULTI-LINK VISION,急性,亞急性,晚期,,,,The cumulative ST rates are based on Kaplan-Meier e

38、stimates.,EXAMINATION 研究-XIENCE的安全性優(yōu)于BMS,支架血栓網(wǎng)絡(luò)薈萃分析 XIENCE是市場上最安全的支架,“目前發(fā)現(xiàn)CoCrEES (XIENCE)較BMS有更低的支架血栓發(fā)生率，如果在將來的研究中得到進(jìn)一步證實(shí)，將會帶來治療模式的巨大轉(zhuǎn)變?！?“有些人認(rèn)為類似于裸支架的產(chǎn)品應(yīng)該具有更低的支架血栓發(fā)生率，并基于此假設(shè)致力于可吸收涂層支架的研發(fā)。這個(gè)研究帶來的發(fā)現(xiàn)可能會讓這些人停下來?！?,Sourc

39、e: 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.

40、1016/S0140-6736(12)60324-9,2602潛在相關(guān)的文獻(xiàn),排除2441篇2117篇沒有對DES進(jìn)行比較324篇是對已有研究的事后分析，亞組分析，隨訪或匯總分析,對161篇文獻(xiàn)進(jìn)行全面審閱,排除112篇84篇文獻(xiàn)不是RCT13篇涉及DES沒有獲得FDA審批11篇研究的支架血栓不是ARC定義4篇是DES匯總分析,共49篇文獻(xiàn)滿足要求,49個(gè)RCT50,844位患者,FDA批準(zhǔn)支架BMS,Cypher,Ta

41、xus,Endeavor,Resolute, Promus Element, Xience,,,,,,支架血栓網(wǎng)絡(luò)薈萃分析 研究設(shè)計(jì),1 and 2 Year Definite Stent Thrombosis Rate Pooled Odds Ratio*,Palmerini et al. The Lancet. March 23, 2012 DOI:10.1016/S0140-6736(12)60324-9,* An odds r

42、atio is a method of comparing whether the probability of an event is the same between two groups,Xience支架血栓發(fā)生率顯著低于所有對照產(chǎn)品,支架血栓網(wǎng)絡(luò)薈萃分析XIENCE是唯一一個(gè)術(shù)后2年支架血栓發(fā)生率低于BMS的DES,Palmerini et al. The Lancet. March 23, 2012 DOI:10.1016/

43、S0140-6736(12)60324-9,與 XIENCE相比支架血栓風(fēng)險(xiǎn)成倍增加一年支架血栓發(fā)生率比值比,支架血栓網(wǎng)絡(luò)薈萃分析 XIENCE是市場上最安全的支架,XIENCE,在真實(shí)世界研究中，持續(xù)一致的低支架血栓發(fā)生率,Source: 1. Smits, PCR 2012. 2.Serruys, PCR 2010. 3.Okkels-Jensen, TCT 2011. 4. Stone, TCT 2010. 5.Windec

44、ker, PCR 2012. 6.Raber, ESC 2010. 8.Smits, TCT 2011. Results from clinical trials are not directly comparable. Information provided for educational purposes.,結(jié)論,XIENCE支架具有出色的安全性表現(xiàn)，并獲得CE批準(zhǔn)，最少使用3個(gè)月DAPT對于臨床工作而言，常規(guī)選擇具有最佳安