COMPARE-ABSORB 1 year results Pieter C. Smits, MD & Robert-Jan van Geuns, MD On behalf of the COMPARE-ABSORB investigators
Steering Committee Stephan Tommaso ACHENBACH GORI Emanuele Victor BARBATO KOCKA Bernard Guiseppe CHEVALIER TARANTINI Peter Robert-Jan SMITS VAN GEUNS Marie-Claude Yoshi MORICE ONUMA Dariusz Jan DUDEK TIJSSEN Javier Nick ESCANED WEST
TOP 10 ENROLLERS Peter Bernard Adrian SMITS CHEVALIER WŁODARCZAK Rotterdam (201) Massy (99) Lubin (178) Nick Tommaso Ralph Mohamed WEST GORI TÖLG ABDEL-WAHAB Cambridge (89) Mainz (72) Bad Segeberg (67) Bad Segeberg (67) Emanuele Giovanni Robert-Jan Mohaned BARBATO VAN GEUNS EGRED ESPOSITO Aalst (66) Rotterdam (55) Newcastle (50) Naples (62)
Hospital del Mar, Hospital Clinic, B. Vaquerizo Monttilla 47 S. Brugaletta 21 Barcelona, Spain Barcelona, Spain G. Tarantini Azienda Ospedaliera, 47 C. Liebetrau Kerckhoff Klinik, 19 Padova, Italie Bad Nauheim, Germany V. Kocka University Hospital Kralovs, 43 G. Saad CHR de la Citadelle, 19 Prague, Czech Republic Liege, Belgium P. O’Kane Royal Bournemouth Hospital, 39 Universitaria di Parma A. Menozzi 17 Bournemouth, UK Parma, Italie P. Buszman American Heart of Poland, 36 J. Fajadet Clinique Pasteur, 15 Chrzanow, Poland Toulouse, France University Hospital, P. Kala 34 C. Cernetti Ospedale San Giacoma, 13 Brno, Czech Republic Castelfranco Veneto, Italie S. Achenbach Universitatsklinikum, 33 Ospedale Papa Giovanni XXIII, O. Valssecchi 12 Erlangen, Germany Bergamo, Italie M. Maly Central Military Hospital, 30 M. Meeuwissen Amphia Ziekenhuis, 11 Prague, Czech Republic Breda, The Netherlands K. Milewski American Heart of Poland, 30 J. Escaned Hospital Clinico San Carlos, 11 Tychy, Poland Madris, Spain S. Ijsselmuiden Albert Schweitzer Hospital, 29 Universitatsklinikum, T. Rudolph 11 Dordrecht, The Netherlands Koln, Germany Charité Campus Benjamin U. Landmesser 29 C. Indolfi Universita Degli Studi Magna Graecia, 6 Berlin, Germany Catanzaro, Italie C. Naber Elisabethkrankenhaus 28 B. Loi Azienda Ospeldaliera Brotzu 6 Essen, Germany Cagliari, Italie P. Tonino Catharina Ziekenhuis, 26 Clinique Saint Hilaire, R. Koning 4 Eindhoven, The Netherlands Rouen, France D. Dudek University Hospital, 25 W. Desmet UZ Leuven, 4 Krakow, Poland Leuven, Belgium H. Nef Universitatsklinikum 25 J. Mehilli Klinikum der Universitat München, 3 Giessen, Germany München, Germany CHU Clermont-Ferrand P. Motreff 25 Universitatsklinikum, P. Lurz 3 Clermont Ferrand Leipzig, Germany J. Sainsous Clinique Rhône Durance, 24 M. Caruso Arnas Civico, 3 Avignon, France Palermo, Italie
COMPARE-ABSORB trial Investigator initiated, prospective, single blind, multicenter randomized controlled trial comparing Xience versus Absorb in a high-risk patient and/or complex lesion population
Study background 25 BES BP-BES Xience EES 13.7 % 20 Cumulative incidence (%) 11.8 % TLF 15 10 5 0 0 180 360 540 720 900 1080 1260 1440 1620 1800 5 year results COMPARE II Days since initial procedure Vlachojannis et al. JACC Cardiovasc Int 2017;10:1215-21
Objectives • To show non-inferiority between Absorb and Xience on TLF at 1 year • Secondary objective is to show superiority of Absorb on TLF between 1 and 5 years in a landmark analysis • Tertiary objective is to show superiority of Absorb on TLF from start to 5 year
COMPARE-ABSORB Inclusion criteria • Patients with at least one of the following: i) High-risk characteristics for restenosis Known diabetes and/or multivessel disease of which more than one de-novo target lesion to be treated with the study scaffold/stent ii) Complex de-novo target lesion - Lesion length >28 mm - Small vessels: RVD between 2.25-2.75 mm - Lesion with pre-existing total occlusion - Bifurcation with single device strategy
COMPARE-ABSORB Exclusion criteria Patient level Lesion / vessel level • Patients at age >75 yr • Target lesion reference • Renal insufficiency vessel diameter < 2.25 and > (GFR <30 ml/min) 4.0 mm • Known LVEF < 30% • STEMI with target lesion RVD • life expectancy < 7 years of >3.5mm • Known non-adherence to • Target lesion with in- DAPT stent/scaffold thrombosis or • Patients on OAC or NOAC re-stenosis • Cardiogenic Shock, Killip >2 • Graft lesions as target lesions • Severe tortuosity of target vessel • Bifurcation target lesion with intended 2 device strategy
Key features of COMPARE-ABSORB Specific patient population and implantation technique • To study a patient population which potentially might benefit the most by the vascular restoration therapy concept on the long term • Selection of specific patients and complex lesions not investigated in previous RCT’s like: STEMI, acute non-STEMI, bifurcations and long lesions and CTO’s • PSP implantation technique from the start
Key features of COMPARE-ABSORB PSP protocol for ABSORB implantation from the start • Pre-dilatation mandatory with 1:1 balloon-artery ratio • Treatment of target vessels < 2.75 mm QCA, IVUS or OCT highly recommended • High pressure (>16 Atm) post-dilatation is mandatory • Post-dilatation with NC balloons up to 0.5 mm larger than the scaffold is recommended
Trial design (original) 1Y 1Y 5Y 5Y Original protocol April 2015 st an nd an 1 st anal alysis: 2 nd anal alysis: Non on-inferiorit y Superi riori rit y in T TLF LF in TLF at 1Y bet w t w een 1 a and 5 45 sites yea ears across Europe ABSOR ORB rd an 3 rd anal alysis: Em er ergent / Cum ulat i t ive R Elec ect ive PCI superiorit y t y in TLF 2100 21 00 pt pt s at at 5Y ( o ( or 7Y) Ran andom om izat at ion on Xience ce aft er er s succes essf sful w iring first t ar arget lesi sion • • TLF LF 1yr r in Xien ence: : 8.5% TLF 1-5yr in Xien TL ence: 10. 10.5% 5% • • Non on-inferiorit y m ar argin: 4.5% TLF 1-5y TL 5yr in ABSORB 6. 6.3% 3% • • Alpha a = 0.05 Pow er= 90% 90% • • Sam ple size: 1004 x 1004 x 2 = 2 = 2008 p 2008 pt s Pow er= 90% 90% • • Sam ple s size 5% at t r t t r. = 2100 p 2100 pt s Sam ple size: 808 x 808 x 2 = 2 = 1616 p 1616 pt s
Study Flow 1200 Patients First Initiated enrolled FDA warning site letter 28 Sep 2015 ABSORB II ABSORB III 600 3 yr results 2 yr results Patients enrolled Start regulatory submission All sites First Patient 100 enrolling enrolled Patients 28 Sep 2015 enrolled Maassstad Hospital July Sep. Dec. May Oct. Nov. March 2016 2017 2015 2015 2015 2016 2016 Follow-up period Enrollment period Study Start-up period
Protocol revisions • Lower limit of small vessels was increased from 2.25 to 2.5 mm • Secondary long term endpoint was changed to 3 to 7 year landmark analysis • Prolonged 36 months DAPT regimen in the scaffold arm was advised
Trial design (revised) Amended protocol 1Y 1Y 3Y 3Y 7Y 7Y April 2017 st an nd an 1 st 2 nd anal alysis: anal alysis: Non on-inferiorit y Superiorit y t y in in TLF at 1Y TLF bet w t w een 3 45 sites and 7 years an across Europe ABSOR ORB rd an 3 rd anal alysis: Em er ergent / Cum ulat i t ive R Elec ect ive PCI superiorit y t y in TLF 21 2100 00 pt pt s at 7Y 7Y ( or 10 10 yr yr) Ran andom om izat at ion on Xience ce aft er er s succes essf sful w iring first t ar arget lesi sion • Chan anged t he secondar ary anal alysis • Ext e t ended t h t he follow -up t o t o 7 years • Excluded t ar arget vessel ref. diam am . < 2.5 m m m • Excluded h high r risk b bleeding pat ient s • Recom m endat ion o on ext e t ension D DAPT
Study flow 1670 AIDA Patients NEJM 2017 enrolled 1200 Patients FDA warning enrolled 31 August letter First Initiated DSMB letter site 28 Sep 2015 ABSORB II ABSORB III Trial put on hold 600 3 yr results 2 yr results Patients 8 September enrolled Commercial Start stop regulatory on ABSORB submission All sites First Patient 100 enrolling Patients enrolled 28 Sep 2015 enrolled Maassstad Hospital July Sep. Dec. May Oct. Nov. March Aug. & Sept. Sept. 2018 2015 2015 2015 2016 2016 2016 2017 2017 Follow-up period Study Start-up Enrollment period period
Study Flow and Follow-up Randomized 1:1 N=1670 (ITT) Xience Absorb N=822 N=848 N = 13 no contact N = 11 no contact N = 13 withdrew consent N = 11 withdrew consent Xience Absorb 1-Year Follow-up N=800 N=822 97.3% Complete 96.9% Complete
Base-line characteristics ABSORB XIENCE Risk factors P value 848 patients 822 patients Age [yr] ± SD 61.9 ± 9.4 62.2 ± 9.0 0.61 Male 79.5% (674) 76.3% (627) 0.13 Diabetes mellitus 34.6% (293) 36.1% (296) 0.57 Current smoker 28.8% (241) 26.9% (217) 0.41 Previous smoker 51.9% (289) 50.1% (280) 0.55 Hypercholesterolemia 66.3% (546) 65.8% (531) 0.88 Hypertension 71.6% (601) 69.2% (567) 0.31 Family history of CAD 36.2% (278) 31.7% (241) 0.07 Previous PCI 27.0% (229) 20.2% (238) 0.38 Previous CABG 1.9% (16) 2.6% (21) 0.41 Previous MI 18.2% (154) 20.2% (166) 0.29 Previous stroke 3.4% (29) 4.8% (39) 0.18 Renal insufficiency 3.9% (33) 6.0% (49) 0.054 LV ejection fraction [%] ± SD 56.4 ± 10.5 56.3 ±10.2 0.83
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