Can Drug-Coated Balloons Work in Synergy with Stent Grafts? BAD KROZINGEN T. Zeller, MD University Heart Center Freiburg-Bad Krozingen Bad Krozingen, Germany Can Drug-Coated Balloons Work in Synergy with Stent Grafts?

Faculty Disclosure Thomas Zeller, MD For the 12 months preceding this presentation, I disclose the following types of financial relationships: Honoraria received from: Abbott Vascular, Angioslide, Bard Peripheral Vascular, Veryan, Biotronik, Boston Scientific Corp., Cook Medical, Cordis Corp., Gore & Associates, Medtronic, Spectranetics, Straub Medical, TriReme, VIVA Physicians Consulted for: Abbott Vascular, Bard Peripheral Vascular, Boston Scientific Corp., Cook Medical, Gore & Associates, Medtronic, Spectranetics Research, clinical trial, or drug study funds received from: 480 biomedical, Bard Peripheral Vascular, Veryan, Biotronik, Cook Medical, Cordis Corp., Gore & Associates, Abbott Vascular, Medtronic, Spectranetics, Terumo, TriReme, Volcano

DCB in SFA Evidence: Proof-of-Concept 7 Trials / 6 DEB Technologies; 6-month LLL (Primary Endpoint) PACCOCATH PTX 3µgr/mm2 + Ultravist ADVANCE PTX PTX 3µgr/mm2 NO Excipient PASSEO 18 LUX PTX 3µgr/mm2 + BTHC LUTONIX PTX 2µgr/mm2 + Polysorbate & Sorbitol IN.PACT PTX 3µgr/mm2 + Urea CVI PTX / Excipient (?) single-arm p=NS [1] G.Tepe et al. - NEJM 2008; [2] M.Werk et al. - Circulation 2008; [3] D.Scheinert - TCT 2012 oral presentation; [4] M.Werk et al. - Circulation CI 2012; [5] D.Scheinert – EuroPCR 2012 oral presentation; [6] D.Scheinert – LINC 2013 oral presentation; [7] S.Duda – EuroPCR 2013 oral presentation

2-Year Primary Patency INPACT SFA vs. Levant 2 ∆ 20.8% Levant 2

DCB Performs Good in the SFA but is not yet Perfect After stenting Bailout-stenting rate up to 40 % (Resilient)

Procedural Characteristics IN.PACT GLOBAL LONG LESIONS IMAGING COHORT: Lesion/procedural characteristics Lesions (N) 164 Lesion Type: de novo restenotic (no ISR) ISR 83.2% (134/161) 16.8% (27/161) 0.0% (0/161) Lesion Length 26.40 ± 8.61 cm Total Occlusions 60.4% (99/164) Calcification Severe 71.8% (117/163) 19.6% (32/163) RVD (mm) 4.594 ± 0.819 Diameter Stenosis (pre-treatment) 90.9% ± 14.2 Dissections: 0 37.9% (61/161) A-C 47.2% (76/161) D-F 14.9% (24/161) Procedural Characteristics Device Success 99.5% (442/444) Procedure Success 99.4% (155/156) Clinical Success 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) Device success: successful delivery, inflation, deflation and retrieval of the intact study balloon device without burst below the RBP 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) Clinical success: procedural success without procedural complications (death, major target limb amputation, thrombosis of the target lesion, or TVR) prior to discharge 6

Primary Patency at 360 days Primary Patency at 390 days IN.PACT GLOBAL LONG LESIONS IMAGING COHORT: Lesion/procedural characteristics Primary Patency at 360 days 91.1% Primary Patency at 390 days 80.7%  10.4% 7

Neointimal Hyperplasia Stent Graft (VIABAHN) Mechanical Barrier Achilles' heel of SFA stenting Original stimulus for stenosis removed from the equation Pore size provides a barrier to tissue ingrowth

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VIASTAR 2-Year Freedom from TLR 79.4% 80% 73% 61.9% log rank p=0.37 log rank p=0.13 Lammer et al . CVIR 2014

25cm Viabahn 12M Data Mean Lesion Length 26.5cm Primary patency: 67% freedom from TLR: 78.2% Primary patency: 67% secondary patency: 96.9% Zeller et al. JEVT 2014

25cm Viabahn 12M Data – Primary Patency Current data is in line with the previously published data of the current generation of the GORE® VIABAHN® Endoprosthesis   % Occlusions at baseline Avg lesion length Primary patency at 1Y 25cm Study 92.9% 26.5cm 67% VIPER 56% >20cm subset 70% VIASTAR 79% 71%

Edge Stenosis - Neointimal Hyperplasia Achilles’ Heel of Viabahn Stent Graft (VIABAHN) Mechanical Barrier Potential Solution: Preparing the landing zone with DCB Pore size provides a barrier to tissue ingrowth through the fabrique but not from the edges

Femoro-popliteal Artery - Biomechanics Zone A Zone B Zone C Zone D Bend / Kink Fixed Compress / Slight curve Lansky, A; Angiographic Analysis of Strut Fractures in the SIROCCO Trial. TCT 2004

Straight Stents Inhibit Shortening Dominant force in vessel is axial compression Up to 23% shortening in native vessel during flexion* Straight stent may limit shortening to around 10%* Risk of kinking at stent end or slack vessel straight stent vessel kink * Smouse BH, Nikanorov A, LaFlash D. Biomechanical forces in the femoropopliteal arterial segment. Endovasc Today. 2005;4:60-66

3D Stent Design vs. Straight Nitinol Stents Test setup replicates adductor canal / proximal popliteal fossa Helical Nitinol stent 150mm stents undergoing 10% compression Straight Nitinol stent Straight stent is Everflex Potential chronic micro injuries at the Viabahn edges

BioMimics 3D vs. Straight Nitinol Stents Test setup replicates adductor canal / proximal popliteal fossa 150mm stents undergoing 10% compression Straight Nitinol stent Proximal Popliteal Fossa Adductor Canal 40mm Straight stent is Everflex 13mm  From VIBRANT 12-month data presentation (G. Ansel); example of bare Nitinol stent fracture PAM 098 Issue 00

DCB & Stentgrafts in Femoro-Popliteal Lesions Conclusions DCB perform well in femoro-popliteal disease Limitations of POBA Dissection Recoil Thrombus Viabahn endoprosthesis provides a mechanical barrier against tissue ingrowth Limitation: Edge stenosis Preparation of the landing zones of the Viabahn stentgraft might solve the limitations of both individual devices Costs? Pathophysiology?