FMRP 2014 | 1 Marc Bosiers Koen Deloose Joren Callaert A.Z. Sint-Blasius, Dendermonde Imelda Hospital, Bonheiden Patrick Peeters Jürgen Verbist OLV Hospital, Aalst Lieven Maene R.Z. Heilig Hart, Tienen Koen Keirse Bart Joos BEC 2014, София RELINE Study: RELINE Study: preliminary 24-month results Koen Deloose, MD

FMRP 2014 | Results with modern angioplasty/stent technology in the SFA 2 THUNDER FEMPAC 12-month Primary Patency (%) FAST – FACT RESILIENT DURABILITY ASTRON VIENNA DURABILITY-200 ZILVER PTX ZILVER PTX long lesions 35%

FMRP 2014 | Mid term failure in the SFA Lesion factors Lesion length Vessel diameter Lesion location Occlusion vs stenosis Patient factors ESRD Diabetics sex 3 Vessel treatment Endoluminal trauma Inflammatory response Neo-intimal proliferation Tissue ingrowth ISR

FMRP 2014 | Mid term failure in the SFA Chemical block Inhibiting smooth muscle cell migration and proliferation DEB DES 4 Mechanical block Creating physical barrier & Remove the stimulus for ISR from the equation Covered stents Shorter TOSAKA I & II (< 15cm) longer TOSAKA II – short TOSAKA III

FMRP 2014 | What does the literature say about stent-grafts for ISR? 5

FMRP 2014 | Endoprosthesis for ISR Literature results 6 N° of patients Average lesion length Primary patency Kazemi TCT Ansel Monahan JVS 2011 Shamerri Ann Saudi Med cm -> non-randomized, single center data

FMRP 2014 | 7 The RELINE Trial Physician initiated, randomized, controled, multi-center trial comparing the new generation Viabahn endoprothesis (Gore & Associates, Flagstaff,AZ) and POBA in the treatment of femoral in-stent restenosis

FMRP 2014 | RELINE study : Participating centers BELGIUM –M. Bosiers, K. Deloose - AZ Sint-Blasius, Dendermonde –P. Peeters, K. Keirse - Imelda Hospital, Bonheiden –J. Hendriks, P. Lauwers, O. D’Archambeau - UZA, Edegem –W. Lansink, G. Lauwers, H. Schroë - ZOL, Genk GERMANY –D. Scheinert, A. Schmidt - Herzzentrum Leipzig –T. Zeller - Herz-zentrum Bad Krozingen –G. Torsello - St Franziskus Hospital, Münster 8

FMRP 2014 | 9 39 VIABAHN Endoprosthesis 44 PTA alone 1:1 randomization 83 patients* Rutherford 2-5 * After Protocol Deviations were excluded RELINE Study

FMRP 2014 | RELINE study : Primary endpoints Primary patency at 12 months –no evidence of restenosis/occlusion within the treated lesion based on CFDU (peak systolic velocity ratio ≤2.5) & without TLR within 12 months serious device‐related adverse events within 30 days post‐procedure 10

FMRP 2014 | RELINE study : Inclusion criteria Rutherford classification 2-5 Ankle‐brachial index ≤0.8 Restenosis/reocclusion in a stent (implanted >30 days) in the superficial femoral artery Total target lesion length between cm (comprising in‐stent restenosis and adjacent stenotic disease) 11

FMRP 2014 | RELINE study: Patient demographics Characteristic VIABAHN ISR N=39 PTA N=44 p-value General Male (%) Female (%) 29 (74.4%) 10 (25.6%) 32 (72.7%) 12 (27.3%) Age (min – max; ±SD) (49 – 86; 9.77) (48 – 86; 9.71) Rutherford categorization Claudication (R 2-3) (%) Critical Limb Ischemia (R 4-5) (%) 34 (87.2%) 5 (12.8%) 36 (81.8%) 8 (18.2%) Rutherford 2 (%) Rutherford 3 (%) Rutherford 4 (%) Rutherford 5 (%) 12 (30.8%) 22 (56.4%) 4 (10.3%) 1 (2.6%) 5 (11.4%) 30 (68.2%) 3 (6.8%) 6 (13.6%)

FMRP 2014 | RELINE study: Patient demographics Characteristic VIABAHN ISR N=39 PTA N=44 p-value Medical history Nicotine abuseNever Current Previous 13 (33.3%) 16 (41.0%) 10 (25.6%) 12 (27.3%) 16 (36.4%) HypertensionNo Yes, medically treated Yes, not medically treated 12 (30.8%) 26 (66.7%) 1 (2.6%) 16 (36.4%) 27 (61.4%) 1 (2.3%) Diabetes MellitusNo Yes, insulin dependent Yes, non-insulin dependent 26 (66.7%) 6 (15.4%) 7 (17.9%) 28 (63.6%) 7 (15.9%) 9 (20.5%) Renal insufficiencyNo Yes 37 (94.9%) 2 (5.1%) 41 (93.2%) 3 (6.8%) HypercholesterolemiaNo Yes 22 (56.4%) 17 (43.6%) 15 (34.1%) 29 (65.9%) ObesityNo Yes 28 (71.8%) 11 (28.2%) 33 (75.0%) 11 (25.0%)

FMRP 2014 | 14 PTA (N=44) Mean Lesion Length 190 (30-270)* stenosis (pre) 75.0 % chronic occlusion 25.0 % acute occlusion 0.0 % Calcified lesion 25.0 %** 8 bail-out procedures after failed PTA Viabahn (N=39) Mean Lesion length 173 (30-330) stenosis (pre)76.9 % chronic occlusion20.5 % acute occlusion 2.6 % Calcified lesion33.3% * Missing data of 3 patients ** Missing data of 1 patient RELINE study

FMRP 2014 | % 95.3 % p=0.383 Number at riskbaseline1MFU6MFU 12MFU PTA Viabahn The Reline Trial: 12 Month Survival:

FMRP 2014 | % 28.0 % p<0.001 The Reline Trial: 12 Month primary patency: Number at risk baseline1MFU6MFU 12MFU PTA Viabahn

FMRP 2014 | % 42.2 % p<0.001 Number at riskbaseline1MFU6MFU 12MFU PTA Viabahn The Reline Trial: 12 Month Freedom from TLR:

FMRP 2014 | 18 The Reline Trial: 24 Month Survival: PRELIMINARY RESULTS 24MFU Number at risk 26 PTA 19Viabahn 88.3 % 92.0 % p=0.531

FMRP 2014 | 19 The Reline Trial: 24 Month primary patency: PRELIMINARY RESULTS 24MFU Number at risk 2 PTA 12Viabahn 61.0 % 10.2 % p<0.001

FMRP 2014 | 20 The Reline Trial: 24 Month Freedom from TLR: PRELIMINARY RESULTS 24MFU Number at risk 5 PTA 12Viabahn 65.2 % 19.8 % p<0.001

FMRP 2014 | Conclusion ISR is the Achilles heel of the current SFA treatment There is some evidence that chemical solutions are valuable in the battle against ISR. The RELINE results proof that a mechanical barrier (like the Viabahn stentgraft) against tissue ingrowth is also a promising tool for treatment of in-stent restenosis, even on the long run… So…. 21

FMRP 2014 | 22 Conclusion …