美敦力新一代藥物洗脫支架的安全性與有效性齊國(guó)先課件

1、中國(guó)醫(yī)大一院心內(nèi)科中國(guó)醫(yī)大一院心內(nèi)科 齊國(guó)先齊國(guó)先2009.5.16 醫(yī)大一院醫(yī)大一院支架模塊設(shè)計(jì)支架模塊設(shè)計(jì)PC 生物相容性多聚物生物相容性多聚物高親脂性的高親脂性的“Zotarolimus” Sprint 輸送系統(tǒng)輸送系統(tǒng)-新新Endeavor Sprint支架輸送系統(tǒng)支架輸送系統(tǒng)Endeavor 2009.5.16 醫(yī)大一院醫(yī)大一院2009.5.16 醫(yī)大一院醫(yī)大一院通過(guò)外徑通過(guò)外徑頭端外徑頭端外徑*Medtronic crossing pro conducted with 3.5 mm x 18 mm Endeavor Sprint, CYPHER SELECT Plus, XIENC

2、E 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 stents; 3.5 mm X 20 mm Taxus Liberte stent. Test data on Medtronic, Inc.2009.5.16 醫(yī)大一院醫(yī)大一院中段桿中段桿近段桿近段桿遠(yuǎn)段桿遠(yuǎn)段桿兩端不透射線標(biāo)記兩端不透射線標(biāo)記Discrete技術(shù)技術(shù):最小化球囊突出最小化球囊突出2009.5.16 醫(yī)大一院醫(yī)大一

3、院Endeavor Sprint在在Endeavor 高輸送性基礎(chǔ)上高輸送性基礎(chǔ)上更加大幅度提高更加大幅度提高使用3.518mm支架進(jìn)行測(cè)試2009.5.16 醫(yī)大一院醫(yī)大一院 2009.5.16 醫(yī)大一院醫(yī)大一院2009.5.16 醫(yī)大一院醫(yī)大一院 2009.5.16 醫(yī)大一院醫(yī)大一院2009.5.16 醫(yī)大一院醫(yī)大一院1 year急性1天晚期 1 個(gè)月 1天 - 1個(gè)月早期 1年1個(gè)月早期支架血栓 30天以內(nèi)2009.5.16 醫(yī)大一院醫(yī)大一院1 個(gè)月1 年晚期 1 個(gè)月 1年極晚期支架血栓 超過(guò)1 年 2009.5.16 醫(yī)大一院醫(yī)大一院Wenaweser et al; J Am Col

4、l Cardiol 2008;52:1134-40Mauri et al; N Engl J Med 2007;356:1020-9.Time since PCI in yearsCumulative Incidence, %543210012342.1% (17) CYPHER Stent (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(jì)發(fā)生率2009.5

5、.16 醫(yī)大一院醫(yī)大一院EndeavorDriver1.5%0.7%P = 0.0710%2%4%6%8%10%0903607201440ARC Def/Prob ST180 270450 540630810900 990 1080 117013501260DaysENDEAVOR Pooled Safety: Mauri, TCT 2008. 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 compa

6、risons. Pooled Kaplan-Meier analysis.2009.5.16 醫(yī)大一院醫(yī)大一院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 /Promus 892 865 NA NA4 Years1. Mauri et al. TCT 2008. 2. Maur

7、i L et al. N Engl J Med. 2007;356:1020-1029.3. Serruys PW et al. ACC 20083. Stone GW et al. PCR 2008.2009.5.16 醫(yī)大一院醫(yī)大一院7.0%4.6%ENDEAVOR Pooled Safety: Mauri, TCT 2008. 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

8、. Pooled Kaplan-Meier analysis.EndeavorDriverP = 0.0150%2%4%6%8%10%0903607201440CD/MI180 270450 540630810900 990 1080 117013501260Days2009.5.16 醫(yī)大一院醫(yī)大一院% DAPT依從性依從性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 optima

9、l duration of dual antiplatelet therapy, specifically 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 置入Endeavor

10、的患者隨訪1年時(shí)只有39% 進(jìn)行雙重抗血小板治療 2009.5.16 醫(yī)大一院醫(yī)大一院2009.5.16 醫(yī)大一院醫(yī)大一院Histopathology快速的快速的藥藥物洗脫物洗脫支架支架設(shè)計(jì)設(shè)計(jì) = 減少減少損傷損傷 (圓潤(rùn)纖細(xì)圓潤(rùn)纖細(xì)的金屬的金屬絲絲)% Drug ElutedTime (Days)65879899PC 基底層基底層 ( 1m)藥物層藥物層90% Zotarolimus10% PC ( 2-4m)Stent Strut生物相容性的生物相容性的 PC安全的配方安全的配方2009.5.16 醫(yī)大一院醫(yī)大一院豬冠脈豬冠脈180 天天BaselineAch (10-5M)mm90da

11、ys2009.5.16 醫(yī)大一院醫(yī)大一院OCT血管血管鏡鏡EndothelialFunctionProximalDistalIVUSZES (n=14) vs. SES (n=16) 8 個(gè)月隨個(gè)月隨訪訪ZES 改善新生內(nèi)膜覆蓋改善新生內(nèi)膜覆蓋 (P=0.0004) 并并且更少血栓形成且更少血栓形成wata et al; J Am Coll Cardiol 2008;52;789-9017個(gè)患者個(gè)患者44 個(gè)重疊個(gè)重疊ZES 6 個(gè)月隨個(gè)月隨訪訪 (24,076 個(gè)金屬個(gè)金屬絲絲分析分析) ZES 無(wú)無(wú)貼貼壁不良壁不良, 100%內(nèi)皮覆蓋內(nèi)皮覆蓋; 無(wú)附無(wú)附壁血栓壁血栓Guagliumi et

12、 al; ESC 2008541 ZES pts 8 個(gè)月隨個(gè)月隨訪訪0.4% 晚期晚期貼貼壁不良壁不良; 無(wú)正性重塑無(wú)正性重塑; 均勻均勻的新生內(nèi)膜分布的新生內(nèi)膜分布Fitzgerald et al; Stanford IVUS core lab ZES (n=20) vs. SES (n=20) vs. BMS (n=10); 乙乙酰酰膽堿膽堿試驗(yàn)試驗(yàn) 6 個(gè)月個(gè)月; ZES較較SES 改善了內(nèi)皮改善了內(nèi)皮功能功能 (P0.001), 和和 BMS結(jié)結(jié)果相似果相似Kim et al; ACC 2008 2009.5.16 醫(yī)大一院醫(yī)大一院2009.5.16 醫(yī)大一院醫(yī)大一院9-12Mont

13、hsTLR 1year靶病變血運(yùn)重建1 年以前和1年以后2009.5.16 醫(yī)大一院醫(yī)大一院TaxusEndeavorFreedom from TLR100%90%95%0306090120150180210240270300330360Time after Initial Procedure (days)TLR-free 95.5%96.8%0.195EndeavorTaxusP (log rank)ENDEAVOR IV 360天無(wú) TLR生存率2009.5.16 醫(yī)大一院醫(yī)大一院Sirius Trial, Holmes et al, Circulation 2004TAXUS IV, S

14、tone et al, Circulation 2004Endeavor II, Fajadet et al. Circulation. 2006;114:98-806.2009.5.16 醫(yī)大一院醫(yī)大一院4.64.1ENDEAVOR II TAXUS IVSIRIUS3.00.620.390.17ENDEAVOR II TAXUS IVSIRIUS0.360.230.249個(gè)月個(gè)月TLR (%)晚期晚期丟丟失失 (mm)支架內(nèi)支架內(nèi)LL (mm) 節(jié)節(jié)段內(nèi)段內(nèi) LL (mm)*12 month analysisData from different clinical trials are n

15、ot suitable for comparison. SIRIUS. Moses et al. NEJM. 2003;349:1315-1323.TAXUS IV. Stone et al. NEJM. 2004;350:221-231.SIRIUS diabetes subset. Circulation. 2004;109:2273-2278.TAXUS IV diabetes subset. J Am Coll Cardiol. 2005;45:1172-1179.Fajadet et al. Circulation. 2006;114:98-806.關(guān)鍵試驗(yàn): 晚期丟失 vs. TL

16、R1-2% 的差別2009.5.16 醫(yī)大一院醫(yī)大一院DES 研究進(jìn)展 4年TLR 標(biāo)志性分析Endeavor II (n=581/598)Sirius (n=501/525)Taxus IV (n=618/650)Days% TLR4 Year Clinical Results of TAXUS IV, Stone, ACC 20064 year Outcomes in the Sirius Trial, Leon, TCT 2006Endeavor II 4 year : Fajadet et al. PCR 20082009.5.16 醫(yī)大一院醫(yī)大一院9-12月TLR 1年靶病變血運(yùn)重建

17、TLR1 年以內(nèi)和1年以后2009.5.16 醫(yī)大一院醫(yī)大一院CypherXienceEndeavorDriver28天兔子動(dòng)脈粥樣硬化血管的內(nèi)皮修復(fù)Atherosclerotic rabbit model, representative healing at 28 days.Presented by Renu Virmani, CRT, 2008.2009.5.16 醫(yī)大一院醫(yī)大一院n/aEndeavor II(n=581/598)Sirius(n=501/525)Taxus IV(n=618/650)5.96.57.27.2R2 = 0.9524024681012345Years of F

18、ollow-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 20064 year Outcomes in the Sirius Trial, Leon, TCT 2006Endeavor II 4 year : Fajadet et al. PCR 20082009.5.16 醫(yī)大

19、一院醫(yī)大一院DES 研究進(jìn)展 隨訪4 年TLR 標(biāo)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 20064 year Outcomes in the Sirius Trial, Leon, TCT 2006Endeavor II 4 year : Fajadet et al. PCR 2008 第一代第一代DES在置入在置入1年后年后TLR危險(xiǎn)因素持續(xù)存在危險(xiǎn)因素持續(xù)存在2009.5.16 醫(yī)大一院

20、醫(yī)大一院1. Mauri et al. TCT 2008. 2. Stone, G. et al. N Engl J Med. 2007;356:998-10082009.5.16 醫(yī)大一院醫(yī)大一院6.7%7.8%310 d940 d10.1%518 d0%5%10%15%20%25%30%0180360540720900108012601440隨訪天數(shù)TLREndeavorCypherTaxusResults come from separate clinical trials. Data may differ in a head-to-head comparison.1. Mauri et al. TCT. 2008. ENDEAVOR Pooled Safety: E I (5 yr), 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. 2007;356:998-1008.2009.5.16 醫(yī)大一院醫(yī)大一院TLR (%)N=322N=7254 yearsEI,EII,EIICA,EIII,EIV,E