BIOTRONIK // Vascular Intervention Orsiro - Hybrid Drug Eluting Stent Clinical Update Dr Michael Nguyen Da Nang 12 Oct 2014 Perth, Western Australia Fiona Stanley Hospital Updated Orsiro movie to promote BIOSCIENCE results available on Orsiro.com and via e-Blast Randomised comparison of a novel, ultrathin strut biodegradable polymer sirolimus-eluting stent with a durable polymer everolimus-eluting stent for percutaneous coronary revascularization NCT01443104  Thomas Pilgrim, MD; Dik Heg, PhD; Marco Roffi, MD; David Tüller, MD;  Olivier Muller, MD; André Vuilliomenet, MD; Stéphane Cook, MD;  Daniel Weilenmann, MD; Christoph Kaiser, MD; Peiman Jamshidi, MD;  Bernhard Meier, MD; Peter Jüni, MD; Stephan Windecker, MD   Department of Cardiology, Swiss Cardiovascular Center, University Hospital, Bern; Institute of Social and Preventive Medicine and Clinical Trials Unit  Bern University Hospital, Switzerland1 PROGRESS WITH METALLIC DRUG-ELUTING STENTS Antiproliferative drug Sirolimus-analogues Paclitaxel SES BES Sirolimus Biolimus ZES SES Zotarolimus EES ZES EES SES Everolimus NES SES SES SES Novolimus Polymer material Durable polymer Biodegradable polymer Platform material & strut thickness 132 140 Stainless steel 120 91 87 81 91 74 60 81 100 64 Cobalt-Chromium/Platinum-Chromium 80 (μm) DURABLE POLYMER EVEROLIMUS-ELUTING STENTS REDUCE THE RISK OF DEFINITE ST, MI AND TVR COMPARED TO NON-EES Baber U et al J Am Coll Cardiol 2011;58:1569-77 Meta-analysis of 17 RCTs with 17,101 patients and mean follow-up of 22 months Definite stent thrombosis Target vessel revascularization Definite ST: RR 0.55, 95% CI 0.38-0.78 TVR: RR 0.77, 95% CI 0.64-0.92 BIODEGRADABLE POLYMER DES REDUCE THE RISK OF DEFINITE ST AND TLR COMPARED TO FIRST GENERATION DES Stefanini GG et al, Eur Heart J 2012;33(10):1214-22 Definite stent thrombosis Studies BP DES DP SES Target lesion revascularization RR (95% CI) Studies BP DES DP SES RR (95% CI) ISAR-TEST 1/202 2/202 0.50 (0.05-5.47) ISAR-TEST 17/202 21/202 0.81 (0.44-1.49) ISAR-TEST 9/1299 9/652 0.50 (0.20-1.26) ISAR-TEST 168/1299 95/652 0.89 (0.70-1.12) LEADERS 20/857 32/850 0.62 (0.36-1.08) LEADERS 88/857 0.79 (0.60-1.02) Overall 0.58 (0.37-0.93) (I2 = 0.0%, p=0.92) 0.1 0.2 0.5 Risk ratio Favours biodegradable Favours durable polymer DES polymer SES Overall 111/850 0.84 (0.71-0.99) (I2 = 0.0%, p=0.79) 0.1 0.2 0.5 10 Risk ratio Favours biodegradable Favours durable polymer DES polymer SES OBJECTIVE  To compare the safety and efficacy of a novel, ultrathin strut, biodegradable polymer based sirolimus-eluting stent with a thin strut, durable polymer everolimus-eluting stent for percutaneous coronary revascularization STENT PLATFORMS ORSIRO Platform material Strut thickness Passive coating Polymer material Antiproliferative drug 10 XIENCE PRIME/XPEDITION Cobalt-Chromium, L-605 Cobalt-Chromium, L-605 60 μm 81 μm Silicon carbide layer Biodegradable Durable PLLA: poly-L-lactic acid PBMA/PVDF-HFP Sirolimus (1.4 μg/mm2) Everolimus (1.0 μg/mm2) ELIGIBILITY FOR PATIENT ENROLLMENT Inclusion criteria Exclusion criteria • Age ≥ 18 years  Pregnancy • Coronary artery disease - stable CAD, silent ischemia - acute coronary syndromes: UA, NSTEMI, and STEMI  Planned surgery within months of PCI • At least one lesion with diameter stenosis >50% in a native coronary artery or a bypass graft - no of vessels: no limitation - no of lesions: no limitation - lesion length: no limitation 14  Intolerance to aspirin, clopidogrel, heparin, sirolimus, everolimus, contrast material  Inability to provide informed consent  Participation in another trial PATIENT RECRUITMENT February 2012 to May 2013 2,119 patients were enrolled across centers in Switzerland Investigator City Patients Thomas Pilgrim, MD Bern 1,216 Marco Roffi, MD Geneva 209 David Tüller, MD Zurich 179 André Vuilliomenet, MD Aarau 102 Olivier Muller, MD Lausanne 101 Stéphane Cook, MD Fribourg 100 Daniel Weilenmann, MD St Gallen 99 Christoph Kaiser, MD Basel 60 Peiman Jamshidi, MD Lucerne 53 16 Basel Aarau Zurich Lucerne Bern Fribourg Lausanne Geneva St Gallen PATIENT FLOW 2,129 patients randomised 2,119 patients included 10 provided preliminary consent but refused definite consent 1,063 allocated to biodegradable polymer sirolimus-eluting stent 1,056 allocated to durable polymer everolimus-eluting stent (1,594 lesions) (1,545 lesions) 1,031 follow-up information for primary endpoint available 1,036 follow-up information for primary endpoint available 1,063 analysed for primary clinical endpoint 1,056 analysed for primary clinical endpoint - 32 censored at timepoint of refusal or loss to follow-up - 20 censored at timepoint of refusal or loss to follow-up 17 BASELINE CHARACTERISTICS BP SES (n=1,063) DP EES (n=1,056) Age (years) — mean ± SD 66.1 ± 11.6 65.9 ± 11.4 Male gender — n (%) 818 (77%) 816 (77%) Diabetes mellitus — n (%) 257 (24%) 229 (22%) Hypertension — n (%) 728 (69%) 706 (67%) Hypercholesterolemia — n (%) 712 (67%) 716 (68%) Previous PCI — n (%) 325 (31%) 292 (28%) Previous CABG — n (%) 113 (11%) 98 (9%) Renal Failure (GFR20 mm) — n (%) 826 (54%) 839 (57%) Small-vessel per lesion (