TNT Session. The latest clinical evidence in diabetics for the Amphilimus TM eluting polymer-free DES. Rafael Romaguera, MD

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1 TNT Session The latest clinical evidence in diabetics for the Amphilimus TM eluting polymer-free DES Rafael Romaguera, MD Hospital de Bellvitge Barcelona Spain

2 Disclosure Statement of Financial Interest Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below. These relationships may lead to bias in my presentation. Affiliation/Financial Relationship Grant/Research Support (Institutional) Consulting Fees/Honoraria Company Abbott Vascular Astra Zeneca, Alvimedica

3 INDEPENDENT STUDIES SPONSORED STUDIES Clinical evidence SAFETY EFFICACY Reduced DAPT duration Diabetic patients Randomized trial (Demonstr8 study) NEXT randomized trial (sub-group DM) U-Short registry - DAPT Randomized trial Cre8 vs ZES (ReCre8) ASTUTE registry - DAPT Real-world study (Particip8) (sub-group DM) RESERVOIR randomized trial (Cre8 vs EES in DM) Matched analysis Cre8 TM vs EES ASTUTE registry - Diabetics Matched analysis Cre8 TM vs BES

4 INDEPENDENT STUDIES SPONSORED STUDIES Clinical evidence SAFETY EFFICACY Reduced DAPT duration Diabetic patients Randomized trial (Demonstr8 study) NEXT randomized trial (sub-group DM) U-Short registry - DAPT Randomized trial Cre8 vs ZES (ReCre8) ASTUTE registry - DAPT Real-world study (Particip8) (sub-group DM) RESERVOIR randomized trial (Cre8 vs EES in DM) Matched analysis Cre8 TM vs EES ASTUTE registry - Diabetics Matched analysis Cre8 TM vs BES

5 The NEXT randomized study Patients with ischemic myocardial symptoms related to de novo lesions (max 2 in 2 different vessels) in native coronary arteries Cre8 TM (n=162 pts) 323 enrolled patients 11 European Sites 100% angiographic f-up 20% IVUS f-up PI: Prof D. Carrié, Toulouse, France TAXUS TM Liberté (n=161 pts) Primary Endpoint: In-stent LLL at 6 months Clinical FU Angiographic/IVUS* FU 1M 6M Y *Angiographic/IVUS Core Lab: BioClinica Leiden, The Netherlands Carrié et al JACC, 2012, 59;

6 Primary Endpoint: 6-month LLL The LLL in the DM subgroup is comparable to that obtained in the overall population

7 % of patients % of patients The NEXT randomized study 5years cumulative TLF (Cardiac death, TV MI, all TLR) Overall population Diabetic population Cre8 (148 pts) TAXUS Liberté (145 pts) p= Cre8 (44 pts) TAXUS Liberté (34 pts) p= % p= p= Hierarchical TLF Cardiac death TV MI TLR 5.5 p= % 13/148 21/145 4/148 3/145 1/148 8/145 13/148 19/ % p= p= /44 9/34 0/148 1/145 0/44 5/34 5/44 7/34 p= % Hierarchical TLF Cardiac death TV MI TLR Comparable TLF and TLR in both overall population and diabetic subgroup for Cre8 TM. This is not the case for Taxus

8 INDEPENDENT STUDIES SPONSORED STUDIES Clinical plan SAFETY Reduced DAPT duration EFFICACY Diabetic patients Randomized trial (Demonstr8 study) NEXT randomized trial (sub-group DM) U-Short registry - DAPT Randomized trial Cre8 vs ZES (ReCre8) ASTUTE registry - DAPT Real-world study (Particip8) (sub-group DM) RESERVOIR randomized trial (Cre8 vs EES in DM) Matched analysis Cre8 TM vs EES ASTUTE registry - Diabetics Matched analysis Cre8 TM vs BES

9 Particip8 Study Design Real world" patients with ischemic myocardial symptoms related to de novo coronary artery lesions, treated with Cre patients 30 European Sites PI: A. Colombo - Italy Pre-specified diabetic subgroup Diabetics patients submitted to angio FU OBJECTIVE: evaluate the safety and efficacy performances of Cre8, in patients comparable to the everyday s clinical practice population, with a specific focus on diabetics subjects PRIMARY ENDPOINT: 6-month incidence of clinical composite endpoint: Cardiac death/ Target vessel MI/ Clinically indicated TLR Clinical FU Angiographic FU (diabetic pre-spec. group) 1M 6M Y

10 Diabetic Population - 12month results - Overall Population - 12month results - Device-Oriented MACE at 1year 3% 12month MACE* = CD + TV MI + CI TLR 2,8% CI: 1.93% ; 3.91% 2% 1% 0,9% 0,9% 1,0% CI: 0.47% ; 1.68% CI: 0.53% ; 1.79% CI: 0.41% ; 1.57% 0% 5% 4% Cardiac Death Target Vessel MI CI TLR MACE 4,7% CI: 2.55% ; 7.63% 3% 2% 1% 1,7% 1,7% CI: 0.55% ; 3.90% CI: 0.55% ; 3.90% 1,4% CI: 0.37% ; 3.42% 0% Cardiac Death Target Vessel MI CI TLR MACE *MACE as percent frequencies of the device oriented clinical composite of CD, TV MI, CI TLR up to 12 months - ITT population - Diabetic population (N = 296) - Adjudicated events

11 INDEPENDENT STUDIES SPONSORED STUDIES Clinical plan SAFETY Reduced DAPT duration EFFICACY Diabetic patients Randomized trial (Demonstr8 study) Real-world study with diabetic sub-group (Particip8) U-Short registry - DAPT Randomized trial Cre8 vs ZES (ReCre8) ASTUTE registry - DAPT Retrospective real-world study (Investig8) Diabetic Randomized study (Reservoir) Matched analysis Cre8 TM vs EES ASTUTE registry - Diabetics Matched analysis Cre8 TM vs BES

12 AES = Cre8 RESERVOIR trial EES = Xience family Exclusion criteria Life-style changes only STEMI Bifurcation>2.5mm Left Main/ostial LAD 3V with CABG indication GFR<30 ml/min LVEF < 30% Contraindication DAPT Primary endpoint: Neointimal volume obstruction by OCT Hospital Clínico San Carlos Madrid

13 RESERVOIR trial Primary endpoint: Neointimal Volume Obstruction AES = Cre8 EES = Xience family p for non-inferiority = Romaguera R, et al. JACC Cardiovasc Interv. 2016; 9: Hospital Clínico San Carlos Madrid

14 Late Lumen Loss (9months) JACC Cardiovasc Interv Jan 11;9(1): Hospital Clínico San Carlos Madrid

15 0,50 0,40 0,30 In-stent LLL results in diabetics 0,20 0,10 0,12 ±0,29 0,16 ±0,13 0,14 ±0,24 0,00 NEXT (diabetic subgroup) PARTICIP8 (diabetic subgroup) RESERVOIR Randomized study All-Comers study Randomized study in DM Company sponsored studies Independent study Hospital Clínico San Carlos Madrid

16 Cum. survival TLR at 3.5 years Polymer-based No polymer 12.1% (EES) 5.2% (Cre8) Days from randomization Log Rank p = 0.195

17 INDEPENDENT STUDIES SPONSORED STUDIES Clinical plan SAFETY Reduced DAPT duration EFFICACY Diabetic patients Randomized trial (Demonstr8 study) Real-world study with diabetic sub-group (Particip8) U-Short registry - DAPT Randomized trial Cre8 vs ZES (ReCre8) ASTUTE registry - DAPT Retrospective real-world study (Investig8) Diabetic Randomized study (Reservoir) Matched analysis Cre8 TM vs EES ASTUTE registry - Diabetics Matched analysis Cre8 TM vs BES

18 Matched analysis: Cre8 vs. BES INSPIRE-1 (Italian Nobori Stent ProspectIve REgistry-1) San Raffaele Scientific Institute Humanitas Clinical Institute Clinica Mediterranea Ospedali Riuniti Marche Nord EMO-GVM Centro Cuore Columbus Policlinico Umberto I Ospedale San Paolo San Raffaele Scientific Institute Clinica Mediterranea Istituto Clinico Città Studi IRCCS Policlinico san Donato EMO-GVM Centro Cuore Columbus Ospedali Riuniti Marche Nord Ospedale San Giovanni di Dio Ospedale San Pietro, FBF Ospedale Santa Corona 18

19 Diabetic cohort TLF/TLR TLF TLR BES Cre8 TM -62% BES Cre8 TM -57% Cre8 is always statistically superior to BES: TLF = 5% vs. 13% (-62%; p<0.001) TLR = 4% vs. 9% (-57%; p=0.005) In press

20 Independent predictors of TLF in the propensity-score matched population Groups Predictor variable Predictor variable in TLF vs non-tlf p-value OR (95% CI) Chronic kidney disease (29.5% vs. 8%) < ( ) Non-DM LVEF ( % vs %) ( ) Total stent length per pt (37.3±19.05 mm vs. 29.9±17.8 mm) ( ) BD-BES vs PF-AES (13% vs. 5%) ( ) DM No of bifurcation per pt ( vs ) ( ) Total stent length per pt (48.0±29.6 mm vs ±22.9 mm) ( )

21 * Study funded by the Spanish Society of Cardiology Second-generation drug-eluting stents in diabetes: a Randomized trial (the SUGAR trial) All-comers DM patients undergoing PCI Amphilimus-Eluting Stents (AES) 1164 patients 26 Spanish Centers Randomization 1:1 Zotarolimus- Eluting Stent (ZES) 12 months Primary Endpoint: TLF (non-inferiority) 24 months Co-Primary Endpoint: TLF (Superiority) PI: Rafael Romaguera Hospital de Bellvitge Co-PI: Pablo Salinas Hosp. Clínico San Carlos

22 Diab8 randomized trial All-comer patients with diabetes mellitus undergoing PCI Cre8 TM EVO 3040 patients 54 International Sites Randomization 1:1 PI: Antonio Colombo Everolimus Eluting Stent (EES) Primary Endpoint EFFICACY = 12 months Target Lesion Revascularization (TLR) Sequential check for Non-inferiority (first step) and then for Superiority (second step) Secondary main Endpoints EFFICACY = 24 months TLR for Superiority SAFETY = 12 months Cardiac Death + Target Vessel MI (CD + TVMI) Clinical FU 1 year 2 years 3 years

23 Conclusions The Cre8 stent represents a different technology than classic polymer-based DES because its design allows formulation of the drug with carriers. This technology has shown in several registries and RCT to be highly effective preventing target lesion failure in patients with DM, with a very low late loss ( ) and a very low rate of events (specially after 6-9 months) in this population. The ongoing large-scale RCT SUGAR and Diab8 will further add evidences to the Cre8 efficacy in the challenging patient population represented by diabetics.

24 Thank you for your attention