美敦力新一代藥物洗脫支架的安全性與有效性_-PPT課件

1、Endeavor Sprint美敦力新一代藥物洗脫支架的安全性與有效性中國醫(yī)大一院心內科 齊國先支架模塊設計PC 生物相容性多聚物高親脂性的“Zotarolimus” Sprint 輸送系統(tǒng)-新Endeavor Sprint支架輸送系統(tǒng)Endeavor Endeavor Sprint 在Endeavor基礎上改良Endeavor Sprint 新工藝出色的Sprinter球囊輸送性用于支架Fulcrum 球囊材質更柔韌更靈活FasTrac 頭端更易于追蹤和穿越病變更短的頭端長度: 3mm 小外徑系統(tǒng)改良近端推送桿特富龍涂層增加潤滑性 增強的傳導鋼絲保證推送力的有效傳遞廣受好評的支架平臺沿用En

2、deavor支架的鈷合金模塊設計,無棱角金屬絲最小化血管內皮損傷輸送性指標柔順性推送性軌跡性通過外徑通過外徑頭端外徑*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 st

3、ents; 3.5 mm X 20 mm Taxus Liberte stent. Test data on file at Medtronic, Inc.小外徑設計為挑戰(zhàn)性病變的治療提供便利Endeavor Sprint 通過外徑和輸送性Endeavor Sprint進一步減小推送桿尺寸:可進行更復雜的器械操作中段桿近段桿遠段桿兩端不透射線標記Discrete技術:最小化球囊突出近段桿中段桿遠段桿Endeavor Sprint1.9F2.8F2.7FEndeavor2.2F3.0F2.7FEndeavor Sprint 最佳輸送有效性利于臨床挑戰(zhàn)更復雜病例Endeavor Sprint在En

4、deavor 高輸送性基礎上更加大幅度提高使用3.518mm支架進行測試優(yōu)化藥物洗脫支架輸送系統(tǒng)醫(yī)生患者更快速的進入目標病變減少血管損傷的風險縮短手術時間挑戰(zhàn)更復雜病變降低手術失敗和血管創(chuàng)傷風險減少手術時間和射線照射量簡化手術、臨床轉歸可預測性增加藥物洗脫支架長期應用：安全性與有效性藥物支架新看點過往晚期丟失TLR (含非臨床驅動）血栓(ARC定義)9-12 個月現(xiàn)在臨床終點TVF臨床驅動TLR 血栓(ARC定義)心源性死亡/心梗 1年DES 安全性: 支架血栓 短期和長期安全性分析:支架血栓發(fā)生的時間點和預測因子1 year急性1天晚期 1 個月 1天 - 1個月早期 1年1個月高壓球囊和雙

5、重抗血小板治療的應用大大降低了30天以內的支架血栓發(fā)生，其主要的危險因素是冠脈的解剖和手術相關因素早期支架血栓 30天以內1 個月1 年晚期 1 個月 1年極晚期支架血栓 超過1 年 極晚期支架血栓是第一代DES應用后才出現(xiàn)的問題，和之前的手術或冠脈解剖因素無關Wenaweser et al; J Am Coll Cardiol 2019;52:1134-40Mauri et al; N Engl J Med 2019;356:1020-9.Time since PCI in yearsCumulative Incidence, %543210012342.1% (17) CYPHER Ste

6、nt (n=878)2.1% (26)TAXUS Stent (n=1401)Cypher & Taxus Pooled Analyses5.7% 95% CICYPHER & TAXUS(n=8,146)Bern-Rotterdam2極晚期支架血栓 第一代DES隨訪4 年累計發(fā)生率1 年以內Endeavor: 0.6%Driver: 1.3%1 年以后 (VLST)Endeavor: 0.1%Driver: 0.2%EndeavorDriverDays03027036072010801440Endeavor2132213121142068203616501087% CI0.0%0.3%0.5

7、%0.6%0.7%0.7%0.7%Driver596595587576570559543% CI0.2%1.2%1.3%1.3%1.3%1.5%1.5%1.5%0.7%P = 0.0710%2%4%6%8%10%0903607201440ARC Def/Prob ST1802704505406308109009901080117013501260DaysENDEAVOR Pooled Safety: Mauri, TCT 2019. 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

8、 values are unadjusted for multiple comparisons. Pooled Kaplan-Meier analysis.ENDEAVOR 臨床研究啟示 隨訪 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%036072010801440ARC (Def/ProbDaysEndeavor 2068 2036 16501087 No. at RiskCypher 863 848 824789 Taxus 1351 1300 11177151 Year2 Years3 YearsPooled DataXience V /

9、Promus 892 865 NA NA4 Years1. Mauri et al. TCT 2019. 2. Mauri L et al. N Engl J Med. 2019;356:1020-1029.3. Serruys PW et al. ACC 20193. Stone GW et al. PCR 2019.DES 研究進展: 極晚期支架血栓ARC (肯定/可能) 支架血栓標志性分析7.0%4.6%Days03027036072010801440Endeavor2132210220802033201916161056% CI1.4%2.0%2.6%2.8%3.4%3.8%4.6%D

10、river596581573561555544529% CI2.5%3.5%4.4%4.5%5.8%6.6%7.0%ENDEAVOR Pooled Safety: Mauri, TCT 2019. 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.EndeavorDriverP = 0.0150%2%4%6%8%10%090360

11、7201440CD/MI1802704505406308109009901080117013501260DaysENDEAVOR 臨床研究啟示 隨訪 4 年 Endeavor比 Driver顯著性降低了心源性死亡/心梗% DAPT依從性DaysE 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, specifica

12、lly 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 臨床試驗DAPT依從性置入Endeavor的患者隨訪1年時只有39% 進行雙重抗血小板治療 Endea

13、vor 為什么能降低極晚期支架血栓(VLST)發(fā)生的風險？藥物洗脫支架長期應用：安全性與療效Histopathology快速的藥物洗脫支架設計 = 減少損傷 (圓潤纖細的金屬絲)% Drug ElutedTime (Days)65879899PC 基底層 ( 1m)藥物層90% Zotarolimus10% PC ( 2-4m)Stent Strut生物相容性的 PC安全的配方ENDEAVOR 安全性涉及因素設計特點% Endotheliazation內皮覆蓋組織學豬冠脈180 天79028180DaysEndeavoreNOS 標記BaselineAch (10-5M)mm90days血管反

14、應性ENDEAVOR 安全性涉及因素動物模型研究OCT血管鏡EndothelialFunctionProximalDistalIVUSZES (n=14) vs. SES (n=16) 8 個月隨訪ZES 改善新生內膜覆蓋 (P=0.0004) 并且更少血栓形成wata et al; J Am Coll Cardiol 2019;52;789-9017個患者44 個重疊ZES 6 個月隨訪 (24,076 個金屬絲分析) ZES 無貼壁不良, 100%內皮覆蓋; 無附壁血栓Guagliumi et al; ESC 2019541 ZES pts 8 個月隨訪0.4% 晚期貼壁不良; 無正性重塑

15、; 均勻的新生內膜分布Fitzgerald et al; Stanford IVUS core lab ZES (n=20) vs. SES (n=20) vs. BMS (n=10); 乙酰膽堿試驗 6 個月; ZES較SES 改善了內皮功能 (P0.001), 和 BMS結果相似Kim et al; ACC 2019ENDEAVOR 安全性涉及因素人體結果 DES 有效性： 靶病變血運重建短期和長期有效性分析: TLR時間點和預測因子藥物洗脫支架長期應用：安全性與療效9-12MonthsTLR 1year靶病變血運重建1 年以前和1年以后與晚期丟失/血管修復相關?與手術相關?與病人相關?與

16、造影相關？TaxusEndeavorFreedom from TLR100%90%95%0306090120150180210240270300330360Time after Initial Procedure (days)TLR030180270360Endeavor773763745719680Taxus775765741716676TLR-free 95.5%96.8%0.195EndeavorTaxusP (log rank)ENDEAVOR IV 360天無 TLR生存率ENDEAVOR IIN = 598TAXUS IVN = 662SIRIUSN = 533RVD (mm)2.

17、732.752.78病變長度 (mm)14.013.414.4支架:病變比例1.841.581.40B2/C 病變 (%)78.450.858.6糖尿病 (%)18.224.425.0LAD (%)434044氯吡格雷/抵克力得治療時間 (月)363包括2.25血管yesnono關鍵試驗患者: DES組相似的基線特征和形態(tài)學Sirius Trial, Holmes et al, Circulation 2019TAXUS IV, Stone et al, Circulation 2019Endeavor II, Fajadet et al. Circulation. 2019;114:98-8

18、06.4.64.1ENDEAVOR IITAXUS IVSIRIUS3.00.620.390.17ENDEAVOR IITAXUS IVSIRIUS0.360.230.249個月TLR (%)晚期丟失 (mm)支架內LL (mm) 節(jié)段內 LL (mm)*12 month analysisData from different clinical trials are not suitable for comparison. SIRIUS. Moses et al. NEJM. 2019;349:1315-1323.TAXUS IV. Stone et al. NEJM. 2019;350:22

19、1-231.SIRIUS diabetes subset. Circulation. 2019;109:2273-2278.TAXUS IV diabetes subset. J Am Coll Cardiol. 2019;45:1172-1179.Fajadet et al. Circulation. 2019;114:98-806.關鍵試驗: 晚期丟失 vs. TLR1-2% 的差別DES 研究進展 4年TLR 標志性分析Endeavor II (n=581/598)Sirius (n=501/525)Taxus IV (n=618/650)Days% TLR4 Year Clinical

20、 Results of TAXUS IV, Stone, ACC 20194 year Outcomes in the Sirius Trial, Leon, TCT 2019Endeavor II 4 year : Fajadet et al. PCR 2019盡管各DES 之間晚期丟失（LL）的差別范圍較大，1年內的TLR差別很小(1-2%) 9-12月TLR 1年靶病變血運重建TLR1 年以內和1年以后與晚期丟失/血管修復相關?與手術相關?與病人相關?與造影相關？與多聚物導致炎癥相關?與病人相關?多聚物影響長期的安全性有效性持久療效源自理想的內皮修復擬生態(tài)和生物相容性的PC多聚物最小化其

21、長期致炎性臨床前研究顯示快速、完全和功能完好的內皮修復CypherXienceEndeavorDriver28天兔子動脈粥樣硬化血管的內皮修復Atherosclerotic rabbit model, representative healing at 28 days.Presented by Renu Virmani, CRT, 2019.n/aEndeavor II(n=581/598)Sirius(n=501/525)Taxus IV(n=618/650)關鍵試驗的TLR: DES 組 每一年的TLR隨訪5.96.57.27.2R2 = 0.9524024681012345Years o

22、f Follow-upTLR (%)4.96.87.99.46.3R2 = 0.9762024681012345Years of Follow-upTLR (%)4.45.66.97.89.1R2 = 0.99730246810Years of Follow-upTLR (%)123454 Year Clinical Results of TAXUS IV, Stone, ACC 20194 year Outcomes in the Sirius Trial, Leon, TCT 2019Endeavor II 4 year : Fajadet et al. PCR 2019DES 研究進展

23、隨訪4 年TLR 標志性研究Endeavor II (n=581/598)Sirius (n=501/525)Taxus IV (n=618/650)Days% TLR4 Year Clinical Results of TAXUS IV, Stone, ACC 20194 year Outcomes in the Sirius Trial, Leon, TCT 2019Endeavor II 4 year : Fajadet et al. PCR 2019 第一代DES在置入1年后TLR危險因素持續(xù)存在ENDEAVOR1N=2132E-I, II, IICA, EIII, EIVCYPHER

24、2N=878RAVEL, SIRIUS, E-SIRIUS, C-SIRIUSTAXUS2N=1752TAXUS I, II, IV, V,VI年齡 (year)626262男性 (%)747272糖尿病 (%)232225高血壓 (%)696472高脂血癥 (%)817170LAD (%)444740RVD (mm)2.732.722.70病變長度 (mm)14.613.814.61. Mauri et al. TCT 2019. 2. Stone, G. et al. N Engl J Med. 2019;356:998-1008累積DES分析基線形態(tài)學6.7%7.8%310 d940 d

25、10.1%518 d0%5%10%15%20%25%30%0180360540720900108012601440隨訪天數(shù)TLREndeavorCypherTaxus75% of TLR with Endeavor75% of TLR with Taxus75% of TLR with CypherResults come from separate clinical trials. Data may differ in a head-to-head comparison.1. Mauri et al. TCT. 2019. ENDEAVOR Pooled Safety: E I (5 yr)

26、, E II (4 yr), E IICA (4 yr), E III (3yr),E IV (2 yr) & E PK (1 yr).2. 3. Stone, G. et al. N Engl J Med. 2019;356:998-1008.DES 試驗4年隨訪數(shù)據(jù)Endeavor, Taxus 和 Cypher 支架TLR發(fā)生時間點差異TLR (%)N=322N=7254 yearsEI,EII,EIICA,EIII,EIV,E-PKN=(2132)N=2132Endeavor試驗累積數(shù)據(jù)分析:第 1和 第4 年 隨訪高危亞組TLR對照 2.5 mmRVD糖尿病AllPatients20 mmLesionseFIVE 12 month data : Ro