藥物支架植入后理想的抗血小板時(shí)間更長(zhǎng)或更短-PPT課件

1、藥物支架植入后理想的抗血小板時(shí)間更長(zhǎng)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 Vascular. BMS?DES?隨著抗拴力度增強(qiáng)，缺血事件 出血并發(fā)癥Thromb Haemost. 2019;103:1128-1135.不同臨床研究中DAPT依從情況Resolute AC雙聯(lián)抗血小

2、板治療1年3年XIENCE V83.5%13.4%Endeavor Resolute84.4%13.8%SPIRIT-COMPARE雙聯(lián)抗血小板治療1年2年XIENCE V78.3%50.0%Taxus77.0%44.5%COMPARE雙聯(lián)抗血小板治療1年2年XIENCE V70%11.4%Promus Element70%15.2%PLATINUM雙聯(lián)抗血小板治療1年2年XIENCE V80.5%48%Promus Element83.4%51.4%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?/p>

3、風(fēng)DAPT過敏腎功能不全、肝功能不全經(jīng)濟(jì)因素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 MonthDAPTSource: 1. Based on patient numbers from various Abbott and non-Abbott trials. Data on file at Abbott Vascular. 2. Trials registered on clinicaltr

4、 as of August 3, 2019. 研究超過 45,000 患者 1100余個(gè) RCT研究及注冊(cè)研究2XIENCE 獲得CE批準(zhǔn) 3個(gè)月DAPTXIENCE CE批準(zhǔn) 3個(gè)月DAPT大量支持?jǐn)?shù)據(jù)XIENCE V USA（2019 PCR）支架血栓大型薈萃分析（2019 TCT）SPIRIT-COMPARE永久性DAPT停用薈萃分析（2019 ACC）真實(shí)世界DAPT中斷研究（2019 PCR）XIENCE V USAXIENCE V USA無對(duì)照注冊(cè)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

5、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 1-Year Results, PCR 2019.Source: James Hermiller, XIENCE V USA 1-Year Results, PCR 2019.Source: Dr. James Hermiller, XIENCE V USA Registry, 1-Year Results, PCR 2019.AP2932510 Rev. A. Information contained herein for

6、distribution outside the USA only. 2019 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 2019 PCRSource: Dr. James Hermiller, XIENCE V USA Registry, 1-Year Results, PCR 2019.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 (3

7、0 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 2019 PCR共計(jì)13,259名植入Xience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

8、需要進(jìn)行至少1年的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 2019.XIENCE大型薈萃分析 -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 2019 TCTXIENCE 大型薈萃分析在超過11,000患者中, XIENCE支架血栓發(fā)生率

9、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 Everolimus Eluting Coronary Stent System Trials. TCT 2019.n=11,219XIENCE 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

10、 from the XIENCEV Everolimus Eluting Coronary Stent System Trials. TCT 2019.n=11,219Stent Thrombosis (%)MonthsXIENCE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(duì)99.4%的患者而言不會(huì)導(dǎo)致支架血栓。” Dr. Gregg StoneSource: Stone, G. Stent Thrombosis and DAPT Interruption: I

11、nsights from the XIENCEV Everolimus Eluting Coronary Stent System Trials. TCT 2019.0.63%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=0.331個(gè)月或1個(gè)月以內(nèi)停用, 2.55%; 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 2019 TCTSPIRIT-COMPARE薈萃分析支架血栓和DAPT永

12、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(píng)估DAPT 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 2019Patients on Dual Antiplatelet TherapyAt 1 YearAt 2 YearsXIENCE V78.3%50.0%Taxus77.0%44.5%匯總數(shù)據(jù)庫(kù)n=678

13、9n=4247XIENCE Vn=4247Taxusn=25422019 ACCSPIRIT-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)間永久性停用DAPT對(duì)支架血栓的發(fā)生率沒有造成影響。” PI KedhiE.Kedhi SPIRIT-COMPARE Meta DAPT Discontinuation, ACC 2019p = 0.75p = 0.052019 ACCDAPT 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

14、斷”包括暫時(shí)及永久停用DAPT的患者Source: Palmerini, T. PCR 2019.研究XIENCE V (n=10,615)研究設(shè)計(jì)患者人群XIENCE V USASPIRIT VSPIRIT WOMENXIENCE V INDIAn=6,516n=1,662n=1,506n=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2019 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)生率支架血栓 ARC 確定的/可能的 (%)0.68%Pooled data of 10,615 patients from four real-world trialsXIE

15、NCE 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 2019.月真實(shí)世界人群(n=10,615)AMI 再狹窄 ACS左主干 分叉病變 糖尿病橋血管 開口病變 EF30%CTO 多支病變 直接支架腎功能不全 多支血管治療2019 PCRXIENCE 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 2019.*

16、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 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2019 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)的研究研究超過 45,000 患者 1隨訪時(shí)間長(zhǎng)達(dá)5 年2100余個(gè)RCT研究及注冊(cè)研究3復(fù)雜病變患者的數(shù)據(jù)包

17、括:左主干AMIACS分叉病變腎功能不全多支病變糖尿病CTOs橋血管再狹窄病變開口病變All statements being made and data shown are reflective of the entire patient 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-y

18、ear patient-related versus stent-related outcomes from the RESOLUTE All Comers trial. The Lancet. April 9, 2019; 377:1241-47; M Krucoff. One-Year Results from the XIENCE V USA Condition of Approval Study, TCT 2019. 1. Based on patient numbers from various Abbott and non-Abbott-sponsored trials. Data

19、 on file at Abbott Vascular. 2. Data from SPIRIT FIRST, SPIRIT II and SPIRIT III trials. 3. Trials registered on as of Aug. 3, 2019. COMPARE研究: 隨訪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

20、 Results. TCT 2019p=0.0007 (log-rank test)69%累計(jì)事件發(fā)生率術(shù)后時(shí)間（天）XIENCE: 與Cypher相比持續(xù)的低支架血栓發(fā)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 de

21、finite 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 directly comparable. Information provided for educational purposes only. Sources: 1L. Okkels Jensen, SORT

22、OUT IV 9-Month Results Presentation. TCT 2019. ST rates are from Kaplan-Meier estimates. 2T. Kimura, RESET 1-Year Results Presentation. ESC 2019. ST rates are from Kaplan-Meier estimates. 3R. Byrne. ISAR Test 4 2-Year Results Presentation. TCT 2019. 4L. Raber, et al. Long-Term Comparison of Everolim

23、us-Eluting and Sirolimus-Eluting Stents for Coronary Revascularization. JACC Vol. 57, No. 21, 2019:214351. Investigator Sponsored StudyRESOLUTE 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研究Source: Windecker S, PCR 2019雙聯(lián)抗血小板治療1年3年XIENCE V83.5%13.4%E

24、ndeavor Resolute84.4%13.8%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=0.050.71%1.43%p=0.10XIENCE Vn=1,130Endeavor Resoluten=1,1203 年確定的支架血栓發(fā)生率支架血栓 (%)Source: 3 year data: Windecke

25、r S, PCR 2019, 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. April 9, 2019;377:1241-47.RESOLUTE All Comers 3年結(jié)果在幾乎所有的臨床終點(diǎn)上，XIENCE

26、均體現(xiàn)出了數(shù)值上的優(yōu)勢(shì)Source: Windecker S, PCR 2019.累積事件發(fā)生率3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%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

27、死亡，全因心梗，全部血運(yùn)重建1年隨訪率98% Source: M. Sabate, EXAMINATION 1-Year Presentation. ESC 2019. Investigator Sponsored Study患者導(dǎo)向復(fù)合終點(diǎn)XIENCE VMULTI-LINK VISIONp-值12.0%14.4%0.16支架相關(guān)終點(diǎn)終點(diǎn)XIENCE VMULTI-LINK VISIONp-值TLR2.2%5.1%0.003TVR3.9%7.0%0.007無篩選STEMI患者 n=1,498XIENCE Vn=741MULTI-LINK VISIONn=747“在臨床表現(xiàn)上，Xience V

28、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 Trialp=0.010.5%1.9%n=751Sources: 1M. Sabate, EXAMINATION 1-Year Presentation. ESC 2019. 2W. Wijns. EXAMINATION Discussant Presentation. ESC 2019. Investigator Sponsored Study1年 ARC 定義確定的支架血栓1n=747 “醫(yī)生通過使用新型的DES

29、，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(duì)早期安全性的擔(dān)憂.” Dr. William Wijns EXAMINATION Discussant, ESC 20192 74%降低EXAMINATION 研究-XIENCE的安全性優(yōu)于BMSSource: M. Sabate, EXAMINATION 1-Year Presentation. ESC 2019. Investigator Sponsored StudyXIENCE Vn=751MULTI-LINK VISIONn=7470.9%2.6%p=0.01ARC定義確定的/可能的支架血栓 1年ARC定義確定的/

30、可能的支架血栓發(fā)生率 (%)3.02.52.01.51.00.50XIENCE 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 estimates. 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(chǎng)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(huì)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

31、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(huì)讓這些人停下來?！?Source: 1Palmerini et al. The Lancet. March 23, 2019 DOI:10.1016/S0140-6736(12)60324-9 2Ormiston. The Lancet, March 23, 2019 DOI:10.1016/S0140-6736(12)60440-1Source: Palmerini et al. The Lancet. March 23, 2019 DOI:10.1016/S0140-6736(12)60324-92602潛在相關(guān)的文獻(xiàn)排除2441篇2117篇沒

32、有對(duì)DES進(jìn)行比較324篇是對(duì)已有研究的事后分析，亞組分析，隨訪或匯總分析對(duì)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,Taxus,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, 2019 DOI:10.1016/S0140-6736(12)60324-9* An odds ratio is a method of