Promise and limitations of DCB in long lesions What Have we Learned from Clinical Trials? Ramon L. Varcoe, MBBS, MS, FRACS, PhD

Promise and limitations of DCB in long lesions What Have we Learned from Clinical Trials? Ramon L. Varcoe, MBBS, MS, FRACS, PhD Associate Professor of Vascular Surgery University of New South Wales Sydney, Australia

Disclosure Speaker name:...ramon L. Varcoe... I have the following potential conflicts of interest to report: Consulting: Medtronic, Abbott Vascular, Boston Employment in industry Stockholder of a healthcare company Owner of a healthcare company Other(s) I do not have any potential conflict of interest

Paclitaxel Drug Resevoirs provide sustained release of the drug over time R. Virmani, CX 2016

What is Known About DCB? 1. They are preferred over simple-pta due to their superior anti-restenotic properties

What is Known About DCB? Giacoppo etal. JACC:Cardiovascular Interventions 2016;9(16):1731-42

What is Known About DCB? 1. They are preferred over simple-pta due to their superior anti-restenotic properties 2. They have an advantage over stents as they leave behind nothing but drug, thus avoiding ISR

What is Known About DCB?

What is Known About DCB? Giacoppo etal. JACC:Cardiovascular Interventions 2016;9(16):1731-42

TASC C & D FEMOROPOPLITEAL LESIONS Particularly challenging May benefit the most from avoiding the full metal jacket

2015 Drug Coated Balloon Treatment for Patients with Intermittent Claudication: New Insights from the IN.PACT Global Study Long Lesion ( 15 cm) Imaging Cohort Dierk Scheinert, MD for the IN.PACT Global Investigators Institution, City, State, Country

IN.PACT Global Clinical Study Largest Real-World, prospective, multicenter, single arm independently adjudicated fem-pop Study All-comers (RC-2-3-4) Bilateral disease Multiple lesions SFA and Popliteal TASC A TASC B TASC C TASC D Ca ++ ISR +1500 Patients 67 Sites in EU, Mid-East, Latin America, Asia Independent Adjudication by Clinical Event Committee Corelab adjudicated (Tot 450-patient imaging cohort of de novo ISR lesions, Long lesions ( 15 cm), CTO lesions ( 5 cm) Patient monitoring: up to 5 years Steering Committee: G.Tepe, M.Bosiers, P.Gaines, D. Dai-Do, A.Razuk, G. Ansel

IN.PACT Global Long Lesion Imaging Cohort: Lesion/Procedural Characteristics Lesions (N) 164 Lesion Type: de novo restenotic (no ISR) ISR Lesion Length 83.2% (134/161) 16.8% (27/161) 0.0% (0/161) 26.40 ± 8.61 cm Total Occlusions 60.4% (99/164) Calcification Severe Diameter Stenosis (pretreatment) 71.8% (117/163) 19.6% (32/163) RVD (mm) 4.594 ± 0.819 90.9% ± 14.2 Dissections: 0 37.9% (61/161) A-C 47.2% (76/161) D-E 13.6% (22/161) F 1.2% (2/161) Device Success [1] 99.5% (442/444) Procedure Success [2] 99.4% (155/156) Clinical Success [3] 99.4% (155/156) Pre-dilatation 89.8% (141/157) Post-dilatation 39.1% (61/156) Provisional Stent - LL 15-25 cm: - LL > 25 cm: 40.4% (63/156) 33.3% (33/99) 52.6% (30/57) 1. Device success: successful delivery, inflation, deflation and retrieval of the intact study balloon device without burst below the RBP 2. Procedure success: residual stenosis of 50% (non-stented subjects) or 30% (stented subjects) by core lab (if core lab was not available then the site reported estimate was used) 3. Clinical success: procedural success without procedural complications (death, major target limb amputation, thrombosis of the target lesion, or TVR) prior to discharge)

IN.PACT Global Long Lesion Imaging Cohort: Kaplan-Meier Estimate of Primary Patency Provisional Stenting 40.4%

IN.PACT Global Long Lesion Imaging Cohort: Primary Patency by Lesion Length Subgroup 97.7% 89.8% 79.2% 63.7%

2015 The Drug-Eluting Balloon Superficial Femoral Artery - Long Study: The DEB SFA-LONG Study Safety and efficacy of the Drug-Eluting Balloon (DEB) for the treatment of the Superficial Femoral Artery (SFA) ischemic vascular disease in symptomatic patients presenting with long lesions: A pilot study Antonio Micari, MD GVM Care & Research Maria Cecilia Hospital Cotignola (RA) Italy prospective, multicentre, single-arm study

Lesion Characteristics The DEB SFA-LONG Study CHARACTERISTIC N=105 Lesion Type Lesion Location De novo Restenotic Ostial Proximal SFA Middle SFA Distal SFA Popliteal 1 Segment 91.4% 8.6% 20% 65.7% 96.2% 71.4% 22.9% Occlusion Rate 49.5% Target Lesion Disease Proximal SFA Middle SFA Distal SFA Popliteal 1 Segment Occluded 19% 40% 27.6% 5.7% Total lesion length in mm: mean (range): 251.71 ±78.89 (150-500) Stenotic 41% 50.5% 37.1% 13.3%

The DEB SFA-LONG Study Cumulative Probability of not having the combined endpoints of clinically-driven target lesion revascularization (TLR) and >50% restenosis Provisional Stenting 10.5% 89.3% 77.2%

2016

2017 Interim Results from Lutonix SFA Long Lesion Study A Prospective, Multicenter, Single-Arm Trial with the Lutonix Drug Coated Balloon for Treatment of Long Lesions in Femoropopliteal Arteries Dierk Scheinert, M.D. Universitätsklinikum Leipzig

Demographics / Procedural Information Lutonix Long Lesion Study Description DCB Subjects (N=118) Age (Years), Mean ± SD (n) 67.6 ± 9.23 (118) BMI >30 kg/m 2 (n/n) 26.3 % (30/114) Diabetes 36.4% (43/118) Baseline Target Limb Rutherford Grade, % (n/n) 2 3 4 24.1% (28/116) 69.0% (80/116) 5.2% (6/116) Baseline ABI of Target Limb, Mean ± SD (n) 0.69 ± 0.26 (111) Highest TASC Classification, % (n/n) B C D 0.8% (1/118) 77.1% (91/118) 22.0% (26/118) Total Target Lesion Length (mm), Mean ± SD (n) 212.5 ± 68.32 (117) Maximum Lesion Length (mm) 450mm Balloons per Subject, Mean ± SD (n) / Range 2.2 ± 0.62 (118) / (1.0, 4.0) CTO, % (n/n) 52.1% (61/117) RVD (mm), Mean ± SD (n) 4.7 ± 0.76 (117) Calcification, % (n/n) 88.1% (104/118)

Freedom from TLR Month 12 Long Lesion SFA LEVANT 2 Study Global Registry Study DCB Subjects Long Lesions Global Registry 87.8% 89.7% 93.4% 94.1% [79.8%, 92.8%] [85.7, 92.7] [87.7%, 96.5%] [92.0%, 95.6%] Primary Patency 68.9% Longer Lesions Comparable Results

Long Lesion DCB Studies 1. D. Scheinert. EuroPCR 2015 2. A. Micari etal. JACC:Cardiovascular Interventions 2015;9:950-6 3. S. Steiner etal. JEVT;2016;23:347-55 4. Schmidt etal. JACC:Cardiovascular Interventions 2016;9:715-24 5. T. Zeller etal. JEVT 2014;21:359-68 6. W. Wu LINC 2017 7. D. Scheinert LINC 2017

Calcification Reduces that Durability of DCB Rx F. Fanelli etal. CVIR 2014; 37:898-907

Conclusion 1. DCB have certain inherent advantages over permanent metallic implant 2. (Early) data suggests DCB appear to be effective in long lesions 3. However, they provide no mechanical support in heavily calcified CTOs 4. In approximately 1/5 will require a provisional stent (combined Rx)