Cải tiến về công nghệ stent ảnh hưởng thế nào đến quyết định can thiệp mạch vành

Ở BỆNH NHÂN NGUY CƠ CAO CÁC CẢI TIẾN VỀ CƠNG NGHỆ VÀ THUỐC CĨ GIÚP CÁC STENT PHỦ THUỐC KHÁC BIỆT NHAU? In high risk patients does stent technology evolution make DES different from each other? VÕ THÀNH NHÂN MD, PhD, FSCAI Disclosure Speaker name: Võ Thành Nhân I have the following potential conflicts of interest to report:  Consulting  Employment in industry  Stockholder of a healthcare company  Owner of a healthcare company  Speaker’s Honoraria: from Abbott, BSc, Medtronic, Terumo, St Jude, Biotronik, Elixir, AGA, B Braun, United Healthcare  I not have any potential conflict of interest Coronary stenting - timeline Restenosis rate 1970 1980 1969 Charles Theodore Dotter invents first coronary stent, experimenting on dogs ~4-5% ~20-30% ~30-40% 1990 1986 Jacques Puel implants first stent minimal LL with DES & 74% reduction in TLR 2000 2008 2nd gen DES: Xience (EES), Endeavor, Resolute (ZES) 2010 2014 DES recommended over BMS in ESC guidelines 2011 Newer Gen DES Orsiro (SES) 2009 DES regain terrain 1970 1980 1990 2000 2010 2006 ESC firestorm, concern about DES safety 1977 Andreas Gruentzig performs first PTCA on human 1999 Adjunctive antiplatelet medication becomes standard Stenting composes 84% of all PCI 2003 Launch of Taxus 2002 Launch of Cypher Important stent characteristics Characteristic Definition Determinants Biocompatibility Resistance to corrosion, thrombosis Materials, coatings, metal surface area Conformability Degree to which an expanded stent can bend around its longitudinal axis Material, stent design Deliverability Ability to deliver stent to target lesion Longitudinal flexibility, crossing profile, trackability, nesting Outer contour Separation of the stent strut from the delivery balloon during insertion around bends Stent design (bigger problems with open or coil designs) Flexibility Degree to which an unexpanded stent can bend around its longitudinal axis Material, stent design Metal surface area Percent of surface area covered by metal after stent deployment Stent design, strut thickness Nesting Security of stent attachment to delivery system Stent design, profile Radial strength Resistance to vessel recoil Stent design, strut thickness Radiopacity Ability to identify stent during fluoroscopy Strut thickness, material Scaffolding Ability of stent to completely cover and support the vessel Material, stent design, strut thickness, metal surface area, radial strength Trackability Ease of movement over guide wire Profile, shaft coating, stiffness, distal tapering “Fish scaling„ Source: Watson and Gorski Invasive Cardiology: A manual for cath lab personnel 2000/ Background • The optimal management of patients at high risk of adverse clinical events remains a challenging clinical problem • Newer-generation DES with durable polymer (DP-DES): – significantly improved safety and efficacy outcomes (death, MI, TVR, stent thrombosis), compared with both BMS and early-generation durable polymer DES; – represent the current standard-of-care for PCI in all patient and lesion subsets • Newer-generation DP-DES in high-risk patients remain associated with higher rates of DES failure, including ISR, TVR and late/very late stent thrombosis Background (Con’t) • Permanent polymer coatings on newer-generation DP-DES: – recently associated with chronic inflammation, hypersensitivity reactions, and neoatherosclerosis, resulting in persisting late thrombotic events; – concerns about long-term durable polymer biocompatibility • Biodegradable polymer DES (BP-DES): - recently introduced to overcome current limitations of newer-generation DP-DES - enhance biocompatibility, promote vascular healing, reduce inflammation and hypersensitivity reactions, and reduce long-term adverse outcomes - safe and effective alternative to newer-generation DP-DES in large all-comers Populations • Long-term potential benefit of BP-DES for the management of high-risk subgroups remains unclear In-Stent Restenosis in High-Risk Subgroup INCIDENCE OF ANGIOGRAPHICALLY DOCUMENTED IN-STENT RESTENOSIS (1998-2009, N=12’904) PREDICTORS OF ISR Cassese S, Heart 2014 LONG-TERM MORTALITY Cassese S, Eur Heart J 2015 Stent Thrombosis in High-Risk Subgroup PREDICTORS AND INCIDENCE OF LATE/VERY LATE STENT THROMBOSIS PREDICTORS OF STENT THROMBOSIS @ YEARS (N=18’334) DEFINITE/PROBABLE STENT THROMBOSIS @ YEAR (N=12’198) HR 3.07 Tada T, J Am Coll Cardiol Intv 2013 Loh JP, Am J Cardiol 2014 Recent Developments in DES Technology Overview of Current Stents Designs NEW METALLIC PLATFORM MATERIALS THINNER STRUTS THINNER, MORE BIOCOMPATIBLE/BIODEGRADABLE POLYMERS NEW LIMUS-ANALOGUES ANTIPROLIFERATIVE DRUGS REDUCED DRUG LOAD IMPROVED CONTROLLED DRUG RELEASE IMPROVE BIOCOMPATIBILITY, REDUCE CHRONIC INFLAMMATION AND HYPERSENSITIVITY REACTIONS Iglesias JF, Minerva Cardioangiologica 2015 (adapted from Stefanini GG, Heart 2014) Newer-Generation Biodegradable Polymer DES ORSIRO® DRUG-ELUTING STENT (BIOTRONIK AG, SWITZERLAND) UNIQUE HYBRID TECHNOLOGY ULTRATHIN STRUTS REDUCE THROMBOGENICITY (PLATELET ADHESION) BIOCOMPATIBLE POLYMER BIOABSORBABLE POLYMER THIN POLYMER COATING REDUCED LIMUS DRUG LOAD REDUCE INFLAMMATORY RESPONSE, IMPROVE ENDOTHELIALIZATION, PROMOTE VASCULAR HEALING Primary Efficacy Composite Endpoint ULTRATHIN-STRUT BP-SES vs THIN-STRUT DP-EES @ YEARS (N=2’119) 12 10.5% - BP SES RR (95%CI)=1.00 (0.77-1.31) P= 0.98 11 10 PRIMARY ENDPOINT TLF @ YEAR 10.4% - DP EES TLF (%) PNON INFERIORITY = 0.0004 6.7% - DP EES 6.7% - BP SES 0 60 120 180 240 300 360 420 480 Days since index procedure Zbinden R, J APimlgrHimea 540 600 660 730 Composites of Primary Efficacy Endpoint ULTRATHIN-STRUT BP-SES vs THIN-STRUT DP-EES @ YEARS (N=2’119) 10.5% - BP SES 10.4% - DP EES 3.2% - DP EES 3.2% - BP SES 0 60 120 180 240 300 360 420 480 540 600 660 730 935 929 924 917 928 918 911 908 907 889 RR (95%CI)=0.91 (0.60-1.39), P=0.67 4.5% - DP EES 4.1% - BP SES Number at risk DP-EES 1056 1036 1033 1030 1030 1022 1014 992 989 988 986 985 BP-SES 1063 1036 1031 1026 1022 1014 1007 988 984 976 974 971 60 120 180 240 300 360 420 480 540 600 660 730 Days since index procedure Number at risk DP-EES 1056 1013 1009 1004 1000 990 981 959 955 953 948 944 BP-SES 1063 1017 1011 1002 995 987 979 957 949 941 936 933 Zbinden R, J Am Heart Assoc 2016 937 922 730 979 960 RR (95%CI)=1.17 (0.81-1.71), P=0.40 6.0% - BP SES 5.1% - DP EES 0 60 120 180 240 300 360 420 480 540 600 660 Days since index procedure TLR clinically driven (%) Days since index procedure Target vessel MI (%) RR (95%CI)=1.01 (0.62-1.63), P=0.98 Number at risk DP-EES 1056 1007 1001 996 988 975 965 940 BP-SES 1063 1012 1002 989 975 967 958 935 Cardiac death (%) RR (95%CI)=1.00 (0.77-1.31), P=0.98 TLF (%) 11 10 60 120 180 240 300 360 420 480 540 600 660 730 Days since index procedure Number at risk DP-EES 1056 1028 1023 1019 1013 1000 990 965 961 955 948 941 BP-SES 1063 1027 1017 1005 992 983 974 950 944 934 929 925 931 908 Subgroup Analysis Primary Efficacy Composite Endpoint ULTRATHIN-STRUT BP-SES vs THIN-STRUT DP-EES @ YEARS (N=2’119) TARGET LESION FAILURE ACROSS PRESPECIFIED SUBGROUPS STRONG SIGNAL TOWARDS A SIGNIFICANT REDUCTION IN TLF IN THE PRESPECIFIED SUBGROUP OF PATIENTS WITH STEMI Zbinden R, J Am Heart Assoc 2016 BIOSCIENCE: STEMI Subgroup Primary Efficacy Composite Endpoint ULTRATHIN-STRUT BP-SES vs THIN-STRUT DP-EES (N=407) TARGET LESION FAILURE @ YEAR 62% RRR 5.4% ARR Pilgrim T, Eurointervention 2015 BIOSCIENCE: STEMI Subgroup Primary Efficacy Composite Endpoint ULTRATHIN-STRUT BP-SES vs THIN-STRUT DP-EES (N=407) TARGET LESION FAILURE @ YEARS DP-DES - 10.8% DP-DES - 8.8% BP-DES - 5.4% BP-DES - 3.4% Piccolo R, JACC Cardiovasc Intv., 2016 Newer-Generation BP-DES vs DP-DES in STEMI BIOSTEMI ClinicalTrials.gov Identifier NCT02579031 Randomized Comparison of a Sirolimus Eluting Orsiro Stent With a Biolimus-eluting Nobori Stent in Patients Treated With PCI DESIGN Randomized, multicenter, all-comer, two-arm, non-inferiority trial OBJECTIVE To compare the safety and efficacy of the sirolimus eluting Orsiro stent and the biolimus-eluting Nobori stent in a populationbased setting, using registry detection of clinically driven events PRINCIPAL INVESTIGATORS Per Thayssen, Odense, Denmark Lisette Okkels Jensen, Odense, Denmark PRIMARY ENDPOINT Target Lesion Failure (TLF) - composite of cardiac death, myocardial infarction (not index procedure related) not related to other than index lesion or TLR) at 12 months Source: Presentation, Lisette Okkels Jensen, EuroPCR 2015 SORT OUT VII NCT01879358 2,525 Patients across centers in Denmark 1:1 randomization Orsiro n = 1,261 Nobori n = 1,264 30-day clinical follow-up 12-month clinical follow-up year clinical follow-up Primary Efficacy and Safety Endpoints SORT OUT VII ULTRATHIN-STRUT BP-SES vs THICK-STRUT BP-BES @ 12 MONTHS (N=2’525) TARGET LESION FAILURE RR 0.83; 95% CI 0.56-1.21; p for non inferiority