1、可降解药物涂层支架临床研究现状,杭州市第一人民医院 王宁夫, Polymer (Degradable) for Drug Excel Sirolimus JW Medical BioMatrix Biolimus A9 Biosensors - Infinnium Paclitaxel/Sirolimus SMT(印度) Nobori Biolimus A9 Terumo - Champion Everolimus Guidant, Polymer (Degradable) Plus Holes for Drug - CoStar Paclitaxel Conor / Biotronik（Co
2、rdis）, No Polymer But Holes for Drug - Janus Tacrolimus Sorin - Taxcor Paclitaxel Eurocor(Germany), No Polymer But Special Stent Surface for Drug - Axxion Paclitaxel Biosensors Yukon Sirolimus Translumina(Germany) - ALA Abciximab Korean AMP Yinyi Paclitaxel Yinyi, Polymer (Nondegradable) for Drug (C
3、onventional DES) - Cypher Select Sirolimus Cordis / Johnson & Johnson - Taxus Libert Paclitaxel Boston Scientific - Endeavor Zotarolimus Medtronic Xience Everolimus Abbott / Guidant Firebird Sirolimus Microport Partner Sirolimus Lepu,Active (Drug-Eluting) Stents,与其他聚合物相比，生物可降解聚合物DES是安全有效的,作为ISAR-TES
4、T-3试验的一部分，由德国国家心脏中心的Adnan Kastrati 教授带领的研究组，随机入选了605例原发冠脉病变患者，分组使用三种西罗莫司洗脱支架：永久聚合物支架，生物可降解聚合物支架及无聚合物支架 June 2008 TCTMD,基线资料,共入选605例，其中糖尿病患者占27.4%，712处病变中74.1%为复杂病变。492例（81.3%）再次造影，两治疗组随访率没有明显差别。 随机分配到各组，其中生物可降解聚合物组（202例），永久性聚合物组（202例），无聚合物组（201例）,死亡、非致死性心梗和支架血栓的发生率,结论,在造影结果和临床结果方面，生物可吸收聚合物支架可完全达到甚至超
5、过永久性聚合物支架。,生物可降解聚合物支架,BioMatrix（Biosensors） Nobori（Terumo） Excel（JW Medical） Infinnium (SMT),BEACON Registry (PI: TH Koh),De Novo /Restenotic Native Coronary Artery Lesions Multi-lesion / Multi-vessel Vessel Diameters: 2.5 4.0 mmStent Diameters: 2.5 4.0 mmLesion Length: 10 mm 28 mmStent Lengths: 8 -
6、 28 mm 8 and 12 mm Lengths for Bailout Only Pre-Dilatation perferred,30 d 6 mo 9 mo 12 mo,Clinical Follow-Up,Primary Endpoint: TVR at 6 months Key Secondary Endpoints: MACE at 30 days, 6 months, 12 monthsClinically driven TLR, TVR at 9 & 12 mosDevice, Lesion and Procedure SuccessAnti-Platelet Therap
7、y at Investigators Discretion,BioMatrix I N = 292 Evaluable,10 Sites in Asia,Prospective, Multi-Center, Electronic Registry(2007),BEACON Registry Patient Characteristics,BioMatrix I 292 PatientsAge 57 (26-83) Diabetes (%) 38 Hypertension (%) 68 Hypercholesterolemia (%) 67 Smoking history (%) 42 Fami
8、ly history of CAD (%) 25 Prior MI (%) 41 Previous PCI (%) 19 Previous CABG (%) 2 Unstable Angina (%) 29 LVEF (%) 56,BEACON Registry Target Lesion Characteristics,ACC/AHA Lesion Classification,Lesion Localization,Count,%,* CTO and any other 100% occluded lesions were not recommended as target lesion
9、(as per protocol - treatment strategy).,n = 393 Target Lesions,BEACON Registry Lesion Characteristics,BEACON Registry Lesion Characteristics,BioMatrix I 393 LesionsLesion length (mm) 16.2 Vessel size (mm) 2.89 Diameter stenosis (%) 82 Stent length (mm) 21 Stents per lesion 1.1 Stents per patient 1.4
10、 Device Success (%) 99.7 Lesion Success (%) 98.8 Procedure Success (%) 95.9,BEACON Registry Clinical Events,%,MACE at 30 Days,2 patients (0.7%) with early stent thrombosis day 5 and day 6,Study Primary Endpoint* - 180 Day TVR,* One patient had two TVRs.,Cumulative,BEACON Registry Clinical Events,BEA
11、CON Registry Clinical Events,%,MACE at 12 Months,No stent thrombosis between 30 days and 12 months,Medistra Excel Drug-ElutIng Stent TRiAl,Predilatation is encouraged, even though direct stenting is allowed in simple lesionStent selection:Try to always use EXCELIf appropriate size / length not avail
12、able, use other DES (Cypher or Taxus)If other DES is not available (logistic problem), use BMSAntiplatelet regimen: ASA 160 mg indefinitely (unless contraindicated)Clopidogrel 300 mg (loading), then 75 mg for 6 months,Methods,All comers, N = 359,2 stent dislodgement* (“prototype stent”),357 eligible
13、 pts,DES-stenting as default strategy (N=993 stents), except if there is logistic problem (BMS will be used),* 1 case when negotiating mildly stenotic, acutely angulated LCX to fix mid-LCX stenosis1 case with diffuse, calcified mid-RCA stenosis, during attempted direct stenting,EXCEL N=607,CYPHER N=
14、178,TAXUS N=111,BMS N=49,BIOMATRIX N=41,ENDEAVOUR N=7,Demographics & CV Risk Factors,N patients 357Age (yrs) 58.8 + 9.7Male / female 297/60Family history 108 (30.2%)Hypertension 192 (53.8%)Dyslipidemia 212 (59.4%)Diabetes mellitus 126 (35.3%)Smoking 162 (45.4%)Prior MI 163 (45.7%)Prior CABG 19 (5.3%
15、)Prior PCI 101 (28.3%),Clinical Presentation,No. patients 357No. lesions 812No. stents 993Clinical presentationStable angina 153 (42.8%)Unstable angina / ACS 42 (11.8%)Acute MI 17(4.8%)Recent MI ( 30 days) 20 (5.6%)Silent ischemia 125 (35.0%)LVEF (%, mean + SD) 58 + 11%,Cumulative Patient Recruitmen
16、t & EXCEL Stent Utilization,2004,2006,N,2005,EXCEL stents,patients,12 months,2007,24 months,Extent of Disease,(38.4%),(35.8%),(21.6%),(2.8%),(0.8%),(0.3%),(0.3%),N of pts,Indication for stenting (n, %),Vessel location (n, %),Types of lesions (n, %),mm,Stent Length (N=993 stents),N of stent,EXCEL (n=
17、607),TAXUS (n=111),BIOMATRIX (n=41): 2.5 mm:19 (46%); 3 mm:9 (22%); 3.5 mm:10 (25%); 4 mm:3 (7%) ENDEAVOUR (n=7): 2.5 mm:3; 3 mm:2; 3.5 mm:2,BMS (n=49),%,%,%,%,Stent Diameter (N=993 stents),CYPHER (n=178),EXCEL in Real World Cases,%,Kaplan Meier Curve: Cumulative TLR and MACE Event Free Survival,Cyp
18、her Taxus EXCEL BMS(n=53) (n=42) (n=191) (n=22) Lesion length(mm) 18.2 18.5 16.5 12.7 Stent size (mm) 2.87 2.84 2.87 3.55 Stent length (mm) 25.2 26.6 22.8 17.0,QCA analysis: 132 pts with 312 lesions. Vessels LM = 8,QCA analysis at 6 months (independent QCA lab NHC, Singapore),Types of Stents used (p
19、er lesion)*,* Biomatrix = 3 & Endeavour = 1 were not included in the analysis,Pre procedural RVD, mm 2.63 2.58 2.55 3.33 MLD, mm 0.92 0.93 0.95 1.30 DS, % 65.6 64.0 62.9 60.7Post procedural RVD, mm 2.61 2.59 2.57 3.23 MLD, mm 2.14 2.09 2.12 2.81 DS, % 17.9 19.2 17.8 12.3 Stent MLD, mm 2.29 2.28 2.34
20、 2.87 In-stent DS, % 11.7 11.7 8.1 10.3Follow-up (6 months) RVD, mm 2.70 2.60 2.66 3.26 MLD, mm 1.94 1.81 2.10 2.22 DS, % 28.1 30.5 21.3 31.5 Stent MLD, mm 2.07 1.94 2.27 2.27 In-stent DS, % 23.0 24.9 14.5 29.7,CYPHER TAXUS EXCEL BMS,QCA analysis at 6 months,Follow-up (6 months)(contd)Late loss, mm
21、In-segment 0.20 0.27 0.02 0.53 In-stent 0.22 0.32 0.08 0.55Restenosis (50%) In-segment 7/52 (13.5%) 3/42 (7.1%) 9/186 (4.8%) 2/19 (10.5%)In-stent 6/52 (11.5%) 2/42 (4.8%) 7/186 (3.8%) 2/19 (10.5%),CYPHER TAXUS EXCEL BMS,QCA analysis at 6 months*,* Biomatrix = 3 & Endeavour = 1 were not included in t
22、he analysis,Cumulative Distribution Curves for EXCEL Stent,Cumulative Distribution Curves for All Stents,CYPHER,EXCEL,TAXUS,BMS,Conclusion,1.Despite the inclusion of challenging “real world cases” (DM, MVD, small vessel, complex lesions, long diffuse disease, calcified stenosis, ostial stenosis, LM,
23、 AMI, CTO, instent restenosis, etc) the preliminary EXCEL results are encouraging, with very low MACE rate & “clean” angiographic appearance of the stent.2. Despite the use of double antiplatelet medictaions for only 6 months, at a follow-up period of up to two years there is no late or very late stent thrombosis,
