Robbert J de Winter, MD PhD FESC TCT 63: One Year Results of the REMEDEE Registry Clinical Outcomes After Deployment of the Abluminal Sirolimus-Coated Bioengineered Stent (COMBO) in a Multicenter, Prospective Postmarket Registry Robbert J de Winter, MD PhD FESC On behalf of the REMEDEE Registry Investigators One Year Results REMEDEE Registry TCT 2015

Disclosure Statement of Financial Interest Robbert J de Winter Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below. Affiliation/Financial Relationship Company Grant/Research Support Consulting Fees/Honoraria Major Stock Shareholder/Equity Royalty Income Ownership/Founder Intellectual Property Rights Other Financial Benefit OrbusNeich; Astra Zeneca; Abbott; Stentys; Tryton; St Jude Medical OrbusNeich -

One Year Results REMEDEE Registry TCT 2015 COMBO stent design Stainless Steel 100 µm Abluminal biodegradable polymer matrix Sirolimus elution EPC capturing technology for accelerated endothelial coverage One Year Results REMEDEE Registry TCT 2015

Abluminal Sirolimus Drug Delivery from a completely biodegradable polymer matrix In vivo elution profile of COMBO and Cypher (% of total drug eluted over time) Polymer matrix resorption within 90 days Granada J et al., Circ Cardiovasc Intervent. 2010; 3:257-266 3

Luminal Endothelial Progenitor Cell (EPC) Capture So this is Genous mechanism One Year Results REMEDEE Registry TCT 2015 G70-0157 Rev 02 4

Combo Dual Therapy Stent Clinical Trial Program Completed Clinical FU Ongoing Prospective, Multicenter Randomized Study REMEDEE N= 61 2-5, 9, 24 Months Completed Single Center Study with Longitudinal OCT Assessment of COMBO’s Healing Profile EGO COMBO REMEDEE OCT Prospective, Multicenter, Randomized Study N= 60 30d, 6, 12 Months Completed N= 1000 Prospective, Multicenter, All-comers Post-market Registry Enrolment Completed REMEDEE Registry Enrolment Commenced Feb 8, 2014 N= 572 Prospective, Multicenter, Randomized Study for Japan and U.S. Approval HARMONEE Japan & US Enrolling N= 1500 Prospective, Multicenter, Randomized Study with Reduced DAPT in ACS Patients REDUCE N= 2500 Prospective, Multicenter, Worldwide All-comers Post-market Registry Enrolling MASCOT Enrolment commencing Q2 2015 N= 436 Prospective, Multicenter, Randomized Study for China Approval COMBO China COSTA N= 900 Prospective, Multicenter, Randomized Study with short Dual Therapy in Patients on Oral Anti-Coagulants In Preparation

One Year Results REMEDEE Registry TCT 2015 Primary objective: To evaluate the immediate and long term safety and performance of the abluminal sirolimus coated bio-engineered stent (COMBO) in routine clinical practice Primary endpoint: Target Lesion Failure Cardiac Death Non-Fatal Target Vessel MI Target Lesion Revascularization One Year Results REMEDEE Registry TCT 2015

One Year Results REMEDEE Registry TCT 2015 All-comers Registry Patients are only excluded from registration if ANY of the following conditions apply: High probability of non-adherence to the follow-up requirements; Currently participating in another investigational drug or device study in which a routine angiographic follow-up is planned; A life expectancy of <1 year; Explicit refusal of participation in the registry. One Year Results REMEDEE Registry TCT 2015

One Year Results REMEDEE Registry TCT 2015 Participating sites Amsterdam, The Netherlands Academic Medical Centre Prof. Dr. de Winter Blaricum, The Netherlands Ter Gooi Ziekenhuizen Dr. Arkenbout Breda, The Netherlands Amphia ziekenhuis Dr. den Heijer Craigavon, UK Craigavon Cardiac Centre Dr. Menown Luxembourg Centre Hospitalier de Luxembourg Dr. Muller Nijmegen, The Netherlands Radboud University Nijmegen Prof. Dr. Suryapranata Riga, Latvia Stradina University Hospital Prof. Dr. Erglis Vigo, Spain Meixoeiro Hospital Dr. Iniguez Zwolle, The Netherlands Isala Klinieken Dr. van ‘t Hof One Year Results REMEDEE Registry TCT 2015

All-comers flash type registry March 14th 2014 June 3rd 2013 One Year Results REMEDEE Registry TCT 2015

Registration per hospital One Year Results REMEDEE Registry TCT 2015

True all-comers registry Min Max Age 34 - 94 years Length 143 - 200 cm Number of risk factors 0/8 - 8/8 Systolic blood pressure 55 - 226 mmHg Lesion length 2 - 117 mm Number of stents 0 - 4 One Year Results REMEDEE Registry TCT 2015

Patient Characteristics n=1000 Age, years 65±11 Sex, male 73.9% Risk Factors Medical History Diabetes 18.4% Congestive heart failure (EF<30%) 3.2% No medication/unknown 9.7% Chronic renal failure 6.1% Oral medication 55.7% Peripheral vascular disease 7% Insulin 34.6% Previous stroke 6% Hypertension 58% Prior myocardial infarction 25.3% Hypercholesterolemia 56.2% Unknown 27.3% Family history of CAD 45.5% In current PCI area 24.9% Smoker 52.3% In other than PCI area 47.8% Previous 28.2% Prior PCI 30.1% Current 24.1% Prior CABG 6.8% One Year Results REMEDEE Registry TCT 2015

One Year Results REMEDEE Registry TCT 2015 Indication for PCI Urgent 30.4% STEMI 58.7% NST-ACS 27.4% Unstable angina 13.9% Elective 69.6% Stabilized STEMI 3.0% Stabilized NST-ACS 15.4% Stabilized unstable angina 9.6% Stable angina and/or documented ischemia 43.6% Angiographic driven 23.2% Other 5.2% One Year Results REMEDEE Registry TCT 2015

Lesion Characteristics Multivessel disease (>1 vessel, >70%) 21.1% Treated lesions (n=1511) Left main 1.3% LAD 50.6% LCx 20.2% RCA 26.1% Bypass graft 1.8% Number of vessels treated One vessel PCI 89.5% Multivessel PCI 10.5% AHA/ACC lesion type A 16.4% B1 24.9% B2 37.5% C 21.1% TIMI flow pre-procedure 14.5% 1 4.5% 2 9.8% 3 71.3% 50% } One Year Results REMEDEE Registry TCT 2015

Lesion Characteristics Length 17.7±10.3 mm Reference vessel diameter 3.2±0.5 Percentage diameter stenosis* 88.4±31.2 % * By visual estimate Thrombus present 15.2 Indication for treatment Native coronary artery 95.4 Venous bypass graft 1.5 Bypass graft 0.1 In-stent restenosis 1.8 In-stent thrombosis Other 1.0 One Year Results REMEDEE Registry TCT 2015

Procedural Characteristics Pre-dilatation 69.9% Number of stents per lesion 1.1±0.37 1 stent per lesion 89.8% >1 stent per lesion 10.2% Stent length 19.3±6.4 Stent length ≤ 15mm 38.7% Stent length > 15mm 61.3% Stent Diameter 3.2±0.4 Stent diameter ≤ 3.0mm 59.4% Stent diameter > 3.0mm 40.5% Stent max pressure (atm) 13.6±3.8 Thrombus aspiration 10.8% Thrombus aspiration in STEMI 83.3% Device success* 98.7% Procedural success† 97.7% One Year Results REMEDEE Registry TCT 2015

One Year Results REMEDEE Registry TCT 2015 Primary Endpoint   N (%) Primary endpoint: TLF 57 5.7 TLF: target lesion failure: a composite of cardiac death, myocardial infarction (MI) (unless documented to arise from the non-treated coronary artery), and target vessel revascularization (TVR). One Year Results REMEDEE Registry TCT 2015

One Year Results REMEDEE Registry TCT 2015 Primary Endpoint   N (%) Primary endpoint: TLF 57 5.7 Cardiac death 17 1.7 Target vessel MI 7 0.7 TLR 43 4.4 TLF: target lesion failure: a composite of cardiac death, myocardial infarction (MI) (unless documented to arise from the non-treated coronary artery), and target vessel revascularization (TVR). One Year Results REMEDEE Registry TCT 2015

One Year Results REMEDEE Registry TCT 2015 Primary Endpoint   N (%) Primary endpoint: TLF 57 5.7 Cardiac death 17 1.7 Target vessel MI 7 0.7 TLR 43 4.4 TVR 48 4.9 Definite ST 5 0.5 Probable ST 1 0.1 TLF: target lesion failure: a composite of cardiac death, myocardial infarction (MI) (unless documented to arise from the non-treated coronary artery), and target vessel revascularization (TVR). One Year Results REMEDEE Registry TCT 2015

Primary endpoint: Target Lesion Failure 5.7% One Year Results REMEDEE Registry TCT 2015

One Year Results REMEDEE Registry TCT 2015 Secundary endpoints Cardiac Death MI 1.7% 0.7% TVR TLR 4.8% 4.4% One Year Results REMEDEE Registry TCT 2015

Comparing REMEDEE Registry with other recent all-comers DES Trials   REMEDEE Registry TWENTE DUTCH PEERS LEADERS COMBO Resolute ZES Xience V EES Promus EES Biomatrix BES Cypher SES N 1000 697 694 906 905 857 850 TLF 5.7 7.9 6.8 6.0 5.0 6.5 7.4 TVF 6.2 8.2 8.1 10.6 12.0 TV-MI 0.7 4.6 2.0 1.0 5.8* 4.6* Cardiac death 1.7 4.9 4.8 4.0 2.1 2.7 Clinically indicated TVR 3.3 3.0 5.8 7.1 Definite ST 0.5 0.6 0.0 0.3 Probable ST (1Y) 0.1 0.8 1.2 0.2 Data are in N or %.The primary outcome is target lesion failure (TLF): a composite of cardiac death, myocardial infarction (MI) (unless documented to arise from the non-treated coronary artery), and target vessel revascularization (TVR). ZES: Zotarolimus Eluting Stent, EES: Everolimus Eluting stent, BES: Biolimus Eluting stent, SES: Sirolimus Eluting Stent . TLR: target lesion revascularization. * TVR and non-TVR myocardial infarction One Year Results REMEDEE Registry TCT 2015

Patient Characteristics Stent Thrombosis Baseline presentation Treated Lesion Days post COMBO stent placement Thrombosis type Repeat revascularization 40-year male STEMI RCA distal <1 Definite balloon angioplasty 83-year female LAD proximal 52-year male 77-year male Stable angina LAD mid stent placement 69-year male Stabilized NST-ACS 9 41-year male 8 Probable* n/a* One Year Results REMEDEE Registry TCT 2015

One Year Results REMEDEE Registry TCT 2015 Stent thrombosis Definite and probable ST 0.6% One Year Results REMEDEE Registry TCT 2015

Strengths & Limitations REMEDEE Registry is a true all-comers study Few exclusion criteria Fast enrollment Balanced contribution of participating centers All events adjudicated by independent clinical events committee The REMEDEE Registry will collect FU untill 5Y REMEDEE Registry is a registry One Year Results REMEDEE Registry TCT 2015

One Year Results REMEDEE Registry TCT 2015 Conclusions REMEDEE Registry is a 1000 patient, true all-comers study Excellent procedural success with COMBO Primary endpoint (TLF) @ 1Y was 5.7% This compares well with results from recent other all-comer trials Definite / probable ST was low and no ST occurred after 9 days post procedure The ongoing COMBO clinical program will provide more data regarding safety and efficacy in different patient populations One Year Results REMEDEE Registry TCT 2015

One Year Results REMEDEE Registry TCT 2015 Study Team Investigators: R.J. de Winter E.K. Arkenbout P. den Heijer I. Menown P. Muller H. Suryapranata A. Erglis A. Iniguez A. van ‘t Hof Research Fellows: D.N. Kalkman P. Woudstra H. Lu M. Beijk Study Nurses: M.I. Klees N. Van Daalen Y. Kwan Chan Vinken Senior Statistician: J.G.P. Tijssen CEC: B. Rensing F. Eeftink Trial Management: G. Peeters One Year Results REMEDEE Registry TCT 2015

One Year Results REMEDEE Registry TCT 2015 This slide shows a list of all the staff and researchers involved in our cardiac emergency department I thank you for your attention Thank You One Year Results REMEDEE Registry TCT 2015 29