EXCELLA BD Randomized Trial 12-month Results Ricardo Costa, MD On behalf of the EXCELLA BD Investigators •••••••• Elixir Medical Confidential Elixir Medical DESyne BDTM Novolimus Eluting Coronary Stent System Platform features DESyne BDTM • Cobalt chromium alloy • Biodegradable polymer stent 81 µm thickness • Thin polymer matrix No primer coating < 3µm coating thickness • Novolimus drug dose of 5 mcg per mm stent length • Active metabolite of Sirolimus degrades in 6-9 months, drug release over 4 weeks • Workhorse DES that leaves behind bare metal surface EXCELLA BD Randomized Clinical Trial RANDOMIZED (3:1), SINGLE BLIND, MULTI-CENTER CLINICAL TRIAL Co-Principal Investigators: A. Abizaid and S.Verheye Angiographic Core Lab: CRC IVUS Core Lab: Stanford University CEC/DSMB: CRC Data Management: CRC Single/Multiple De Novo Native Coronary Artery Lesions (A-B2) Vessel Diameters: 2.5-3.5 mm Stent Diameters: 2.5-3.5 mm Lesion Length: ≤24 mm Stent Lengths: 14 - 28 mm Pre-Dilatation required/ Post-Dilatation at physicians discretion Cobalt Alloy Stent + Bioabsorbable Polymer + Novolimus @ 5µg per mm Stent Length DESyne BD DES n= 115 Clinical Follow-up Angiographic/IVUS (Subset) Follow-up Clinical Follow-up Primary Endpoint: Key Secondary Endpoints: Anti-Platelet Therapy for 12 months Geography: Belgium, Germany and Brazil 30d 6mo 9mo 12mo ENDEAVOR DES Control n= 31 2-5yrs In-Stent Late Lumen Loss at 6 months (QCA) Device and Procedure (Clinical) Success Device-oriented composite endpoint (Death, MI, or TLR) at 1, 6, 9, 12mo and 2-5 yrs Clinically driven TLR, TVR and TVF at 1, 6, 9, 12mo and 2-5 yrs Stent thrombosis rates at 1, 6, 9, 12mo and 2-5yrs ABR, LLL and % volume obstruction at 6 months EXCELLA BD Study Organization Principal Investigators Clinical Event Committee • • • • • Alexandre Abizaid Stefan Verheye Steering Committee: • • • Alexandre Abizaid Stefan Verheye Peter Fitzgerald DSMB • • • Otavio Berwanger Adriana Moreira Ricardo Pavenello Aurea Chaves Dimytri Siqueira Sergio Braga Angiographic Core Lab • Cardiovascular Research Center, Sao Paulo, Brazil IVUS Core Lab • Stanford University – Peter Fitzgerald Date Coordination Center • Cardiovascular Research Center, Sao Paulo, Brazil EXCELLA BD Investigators J. SCHOFER A. ABIZAID R. BOTELHO S. VERHEYE K.E. HAUPTMANN M. PERIN H. CASTELLO M. WIEMER C. DUBOIS M. WAINSTEIN HAMBURG - GERMANY SAO PAULO, BRAZIL UBERLANDIA, BRAZIL ANTWERPEN - BELGIUM TRIER - GERMANY SAO PAULO, BRAZIL SAO PAULO, BRAZIL BAD OEYNHAUSEN - GERMANY LEUVEN - BELGIUM PORTO ALEGRE, BRAZIL 42 28 24 23 13 6 6 5 3 1 Patient Flow and Follow-up 151 patients (NL=168) enrolled and randomized 1 Deregistered 3 Withdrew consent 3 no study stent 1 Deregistered Zotarolimus-eluting stent N=31 pts (NL=38) Novolimus-eluting stent N=115 pts (NL=127) 6-day clinical FUP N=115 pts 6-month clinical FUP N=113 pts 6-month angio FUP N=107 pts (NL= 119) (NIVUS = 35) Clinical FUP 100% Clinical FUP 98.6% Angio FUP 94.5% Intention to treat analysis Pts, patients; NL number of lesions; NIVUS number of IVUS 9-month clinical FUP N=31 pts 6-month clinical FUP N=31 pts 6-month angio FUP N=31 pts (NL= 38) (NIVUS = 16) Baseline Patient Characteristics DESyne BD (N=115 patients) ZES (N=31 patients) 65.0±9.3 60.4±10* Male 63.5% 77.4% Diabetes mellitus 28.7% 25.8% Current Smoker 18.3% 29.0% Hypercholesterolemia 72.2% 80.7% Hypertension 80.9% 80.7% Previous myocardial infarction 25.2% 32.3% Previous CABG 5.2% 0.0% Previous PCI 20.0% 25.8% Unstable angina 10.4% 9.7% Patient Characteristics Age, years (± SD) *p=0.028; all others p=ns Baseline Lesion Characteristics DESyne BD (N=127 lesions) ZES (N=38 lesions) Left anterior descending 43.3% 39.5% Left Circumflex 27.6% 21.1% Right coronary artery 29.1% 39.5% 16.5% 21.1% 14.59±5.53 15.30±5.29 2.94±0.38 3.1% 34.6% 0.8% 7.9% 3.01±0.46 2.6% 36.8% 0% 5.5% Lesion Characteristics Target Vessel AHA/ACC Lesion class C Lesion Length, mm (± SD) Reference Vessel, mm (± SD) Ostial Lesion Moderate to Heavy Calcification Thrombus Bifurcation p=ns for all characteristics Angiographic Results 6 months In-Stent Analysis Novolimus Zotarolimus N(L)=119 N(L)= 38 Post-procedure 3.00±0.37 3.08±0.35 0.31 At 6-months 2.95±0.37 2.99±0.38 0.67 Acute gain 1.87±0.42 2.01±0.43 0.09 MLD post-procedure 2.76±0.37 2.90±0.34 0.04 MLD at 6-months 2.64±0.39 2.22±0.53 <0.001 LLL at 6-months (in-stent) 0.12±0.15 0.67±0.47 < 0.001 8.5±44 6.2±4.5 0.002 11.0±6.6 25.6±15.1 < 0.001 0.0% 7.9% 0.003 RVD. mm P value MLD / Late Lumen loss (LLL), (mm) Diameter Stenosis (%) Post-procedure At 6-months Binary Restenosis (%) (in-stent) Primary Endpoint Analysis: 6-month In-Stent Late Lumen Loss Novolimus Zotarolimus DELTA* (Upper 1-sided 95% CI) Non-inferiority P value Superiority P value 0.12 0.67 -0.55 (-0.44) <0.001 <0.001 *Least square means Superior -0.60 -0.50 Zone of non-inferiority Pre-specified margin=0.20mm Zone of noninferiority Zone of Superiority -0.40 -0.30 -0.20 -0.10 0.00 0.10 Zone of inferiority 0.20 0.30 0.40 Upper one-sided 95% CI Met Primary Non-Inferiority Endpoint and Superiority Endpoint Clinical Results –12 months DESyne (N=112) Endeavor (N= 31) P-Value 2.7% 3.2% 1.00 CARDIAC DEATH 0.0% 0.0% -- TARGET VESSEL MI 0.9% 0.0% 1.00 CLINICALLY-INDICATED TLR 1.8% 3.2% 0.52 0 to 360 days, % (n) HIERARCHICAL EVENTS DEVICE ORIENTATED COMPOSITE -Definite/Probable Stent Thrombosis 0.0% 0.0% Modified Intention to Treat (patients who received a study stent) Cardiac Events at 12 months 3.5% 3.2% 3.0% 2.7% 2.5% 1.8% 2.0% 1.5% 0.9% 1.0% 0.5% 0.0% 0.0% 0.0% DESyne BD 12m Cardiac Death TV-MI 0.0% Endeavor 12m CI-TLR MACE (TLR, Cardiac Death, MI) 3.2% Conclusions • The EXCELLA BD trial demonstrated both non-inferiority and superiority of the Elixir DESynetm BD Novolimus eluting stent compared to control for the primary endpoint of in-stent late lumen loss at 6 months • Angiographic binary restenosis for the DESyne BD stent was significantly less compared to control (0.0% vs. 7.9%, p=0.003) • The composite endpoint of cardiac death, TV-MI and CI-TLR remains low and unchanged from 6 months for both groups demonstrating clinical safety of the Elixir DESyne BD stent • There was no reported stent thrombosis through 12 months