Eric J Dippel, MD FACC Davenport, Iowa, USA February 19, 2017 What is the Ideal Treatment Strategy for Fem-Pop In-Stent Restenosis: Laser, DCB, DES, or Covered Stent? Eric J Dippel, MD FACC Davenport, Iowa, USA February 19, 2017

Conflict of Interest Consultant Shareholder Abbott Vascular Bard Boston Scientific Covidien Medtronic Spectranetics WL Gore Shareholder

Global PAD/ISR Scope of Problem >200M People Living with PAD Globally <2% Treated Surgically or Endovascularly >400,000 FemPop Stents Implanted WW Every Year 250,000 ISR Cases U.S. ISR Incidence >200,000 Stents / Year implanted Stent volume growing 6-7% annually 30-40% 1st time ISR Incidence within 2 years of implant 115,000 US ISR Cases

Histology Neointimal hyperplasia 15% cellular 85% extracellular matrix Very high water content

EXCITE ISR Trial Overview DESIGN: Prospective, randomized, multi-center clinical evaluation of excimer laser atherectomy (ELA) for ISR Primary Safety Endpoint: Major Adverse Events (MAE) during hospitalization through 37-day follow-up to include all death, unplanned major amputation, or target lesion revascularization Primary Effectiveness Endpoint: Freedom from clinically driven TLR through 6 month follow-up (212 days) 252 patients enrolled between June 2011 and March 2014 in 40 clinical sites in US 7 lesions uncrossable 252 lesions crossable by guidewire 170 ELA + PTA 82 PTA Primary Safety endpoint at 37 days (n=158) Primary Safety endpoint at 37 days (n=77) Primary Efficacy endpoint at 212 days (n=157) Primary Efficacy endpoint at 212 days (n=73) Dippel et al. JACC CI. 2015;8:92-101

Baseline Lesion Characteristics Angiographic Core Lab Assessment ELA + PTA (N=169) PTA Alone (N=81) P-value Mean Lesion Length (cm) 19.6 19.3 0.85 Diameter Stenosis (%) 81.7% 83.5% 0.42 Popliteal Lesion 21.3%  23.4%  0.93 Total Occlusion 30.5% 36.8% 0.37 Calcium (Mod/Sev) 27.1% 9.1% 0.005 Stent Fracture 0.16 85.8% 95.8% 1 5.0% 0.0% 2 6.4% 4.2% 3 2.1% 4 5 0.7% 20% of lesions were > 30 cm in length Dippel et al. JACC CI. 2015;8:92-101

Product-Limit Survival Estimates Freedom from TLR Survival Probability Product-Limit Survival Estimates With number of subjects at risk Days from Index Procedure p < 0.003 365 Dippel et al. JACC CI. 2015;8:92-101

Product-Limit Survival Estimates Freedom from MAE Survival Probability Product-Limit Survival Estimates With number of subjects at risk Days from Index Procedure p < 0.001 365 Dippel et al. JACC CI. 2015;8:92-101

Variable (Lesion Length) Lesion Length and TLR Favors ELA & PTA Favors PTA Variable (Lesion Length) Estimate Lower CL Upper CL 5 cm 0.96 0.43 2.14 15 cm 0.66 0.39 1.12 25 cm 0.46 0.29 0.70 35 cm 0.31 0.17 0.58 Risk Estimate Dippel et al. JACC CI. 2015;8:92-101

DEB Experience in SFA ISR 3 Prospective Registries IN.PACT SFA ISR DEBATE-ISR PLAISIR 4 Prospective Randomized Control Trials PACUBA FAIR COPA CABANNA ISAR-PEBIS—on going

PACUBA study Prospective Randomized 1:1 Single center N = 60 (planned) EuroCor balloon No core lab Lammer J, et al. Veith. 2011

FAIR study Prospective Multi-center Primary end pt binary restenosis IN.PACT balloon Ave length 82 mm Core lab Krankberg H, et al. LINC 2015

COPA COBANNA study Prospective Multi-center Primary end point LLL by DSA N = 88 Cotavance balloon Ave length 119 mm Core lab Krankberg H, et al. LINC 2015

Zilver PTX Global Registry

Zilver PTX Global Registry

100 patients enrolled in 7 clinical sites in Europe RELINE Trial Overview DESIGN: Prospective, randomized, multi-center clinical evaluation of Viabahn for ISR Primary Safety Endpoint: Major Adverse Events (MAE) during hospitalization through 30 day follow-up to include all death, unplanned major amputation, or target lesion revascularization Primary Effectiveness Endpoint: Primary patency at 12mth, PSVR>2.5 100 patients enrolled in 7 clinical sites in Europe 47 Viabahn 53 PTA 8 Excluded 9 Excluded 39 pts analyzed 44 pts analyzed Deloose K. LINC 2014

RELINE Demographics and Lesion Characteristics Deloose K. LINC 2014

RELINE Efficacy Safety non-inferior Deloose K. LINC 2014

General & Angiographic Screening Lesion gradient <15mmHg SALVAGE Study Design Femoropopliteal artery in-stent restenosis (ISR) Prospective registry 9 US sites Anticipated enrollment 100 pts Actual enrollment 27 pts Enrolled Viabahn Yes General & Angiographic Screening ELA + PTA Lesion gradient <15mmHg No Viabahn Screen failure No Primary endpoint 12mth patency Laird et al. Cath Card Interv. 2012;80:852-859

2 mm Turbo Elite laser pilot channel 8 Fr Turbo Booster sheath 6x100 PTA 3mmHg gradient 6x150, 6x50 Viabahn

Photo PAC study Prospective Single-center Primary end pt binary restenosis N = 14 Laser atherectomy IN.PACT balloon Ave length 133 mm Mean f/u 19 mths Duplex PSVR>2.4 No core lab One pt had restensois and TLR at 36 mths Van den Berg J et al. J Invas Card. 2014;26(7):333-337.

Conclusions A new paradigm is emerging for the treatment of FemPop ISR PTA alone has failed against 3 different treatment strategies DCB is effective for lesions less than 10cm More data is needed for Tosaka 3, cost effectiveness DES is effective for moderate length lesions Not FDA approved Both laser atherectomy and Viabahn are effective for long lesions Both are FDA approved for ISR Combination therapy needs further investigation