RELINE-trial : 24 months results with the Viabahn vs PTA for in-stent restenosis

LINC 2015, Leipzig A.Z. Sint-Blasius, Dendermonde Marc Bosiers Koen Deloose Joren Callaert Imelda Hospital, Bonheiden Patrick Peeters Jürgen Verbist OLV Hospital, Aalst RELINE-trial : 24 months results with the Viabahn vs PTA for in-stent restenosis Lieven Maene Roel Beelen R.Z. Heilig Hart, Tienen Koen Keirse Bart Joos Koen Deloose, MD FMRP 2015 1

Disclosure slide I have the following potential conflicts of interest to report: Consulting Employment in industry Stockholder of a healthcare company Owner of a healthcare company Other(s) I do not have any potential conflict of interest FMRP 2015 2

The results of modern generation stents? 1 yr ppr 1 yr CD-TLR mean LL 20-25% in-stent restenosis 85,5% 86% 80,4% 78% 22,6 9,9 6,2 6,6 9,0% Zilver PTX Complete SE Tigris Biomimics Resilient Stroll Durability II Durability I Supera Viastar Supera LL [1] Dake MD et al. Circ Cardiovasc Interv. 2011; [2] Scheinert D LINC 2013; [3] Laird JR et al. Circ Cardiovasc Interv. 2010; [4] Cordis SMART Control IFU 100000000922.1; [5] Matsumura JS J Vasc Surg. 2013;; [6] Bosiers M J Endovasc Ther. 2009; [7] Lammer J et al. J Am Coll Cardiol. 2013 With the courtesy of Medtronic Academia of Medical Education FMRP 2015 3

The results of modern generation stents? 20-25% in-stent restenosis Chemical block Inhibiting smooth muscle cell migration and proliferation Mechanical block Creating physical barrier & Remove the stimulus for ISR from the equation DEB DES Covered stents FMRP 2015 4

Chemical block Inhibiting SMC migration & proliferation : DEB Stabile et al. : single center registry (39 patients) on the use of DCB (IN.pact Admiral Medtronic) for treatment of femoral ISR (JACC 2012;60:1739-1742) Primary patency : 92.2% @ 12 months Primary patency : 70.3% @ 24 months FMRP 2015 5

Chemical block Inhibiting SMC migration & proliferation : DEB Liistro et al. : DEBATE ISR : single center registry on the use of DCB (IN.pact Admiral Medtronic ) for treatment of femoral ISR (JACC 2012:60:B97) 44 patients DCB vs historical cohort POBA (42) ; 100% diabetics MLL 131 mm PPR @ 12 months 80.5% - Freedom from TLR : 86.4% @ 12 months ; 68% @ 24 months FMRP 2015 6

Chemical block Inhibiting SMC migration & proliferation : DEB Krankenberg et al. : FAIR trial : multi-center randomized, controled trial on the use of DCB (IN.pact Admiral Medtronic ) and POBA for treatment of femoral ISR 119 patients : 62 DCB vs 57 POBA ; MLL 82 mm PPR @ 12 months 70.5% Presented @ LINC 2014, Leipzig, Germany Freedom from TLR : 90.8% @ 12 months FMRP 2015 7

Chemical block Inhibiting SMC migration & proliferation : DES Zilver PTX Single Arm Study, 787 patients, 119 ISR lesions, mll 133mm Zeller et al. JACC 2013;6:274-81 FMRP 2015 8

Mechanical block Creating physical barrier : Covered stents N of patients Average lesion length Primary patency Kazemi TCT 2006 Ansel 2007 Monahan JVS 2011 17 15 cm 65% @12M 27 26 cm 52% @18M 24 N/A 62% @12M Shamerri Ann Saudi Med 2012 24 24.5 cm 85.1%@12M -> non-randomized, single center data FMRP 2015 9

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 2015 10

The RELINE Trial 1:1 randomization 83 patients* Physician initiated, Rutherford randomized, 2-5 controled, multi-center trial comparing the new generation Viabahn endoprothesis (Gore & Associates, Flagstaff,AZ) and POBA in the treatment of femoral in-stent restenosis * After Protocol Deviations were excluded FMRP 2015 11

RELINE study : 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 Primary Patency at 24 months No evidence of restenosis/occlusion within the treated lesion based on CFDU (peak systolic velocity ratio 2.5) & without TLR within 24 months FMRP 2015 12

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 4-27 cm (comprising in stent restenosis and adjacent stenotic disease) FMRP 2015 13

RELINE study: Patient demographics Characteristic VIABAHN ISR N=39 General PTA N=44 p-value Male (%) Female (%) Age (min max; ±SD) 29 (74.4%) 10 (25.6%) 67.69 (49 86; 9.77) 32 (72.7%) 12 (27.3%) 68.98 (48 86; 9.71) 0.853 0.791 Rutherford categorization Claudication (R 2-3) (%) Critical Limb Ischemia (R 4-5) (%) 34 (87.2%) 5 (12.8%) 36 (81.8%) 8 (18.2%) 0.508 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%) 0.065 FMRP 2015 14

RELINE study: Patient demographics Nicotine abuse Hypertension Diabetes Mellitus Renal insufficiency Hypercholesterolemia Obesity Characteristic Medical history Never Current Previous No Yes, medically treated Yes, not medically treated No Yes, insulin dependent Yes, non-insulin dependent No Yes No Yes No Yes VIABAHN ISR N=39 13 (33.3%) 16 (41.0%) 10 (25.6%) 12 (30.8%) 26 (66.7%) 1 (2.6%) 26 (66.7%) 6 (15.4%) 7 (17.9%) 37 (94.9%) 2 (5.1%) 22 (56.4%) 17 (43.6%) 28 (71.8%) 11 (28.2%) PTA N=44 12 (27.3%) 16 (36.4%) 16 (36.4%) 16 (36.4%) 27 (61.4%) 1 (2.3%) 28 (63.6%) 7 (15.9%) 9 (20.5%) 41 (93.2%) 3 (6.8%) 15 (34.1%) 29 (65.9%) 33 (75.0%) 11 (25.0%) p-value 0.569 0.865 0.951 0.889 0.069 0.935 FMRP 2015 15

The RELINE Trial : lesion characteristics Viabahn (N=39) PTA (N=44) Mean Lesion length 173 (30-330) Mean Lesion Length 190 (30-270)* stenosis (pre) 76.9 % stenosis (pre) 75.0 % chronic occlusion 20.5 % chronic occlusion 25.0 % acute occlusion 2.6 % acute occlusion 0.0 % Calcified lesion 33.3% Calcified lesion 25.0 %** 9 bail-out procedures after failed PTA FMRP 2015 16 * Missing data of 3 patients - ** Missing data of 1 patient

The RELINE Trial : 1 2 yr survival 1 year 2 year 91.9 % 86.1 % 95.3 % 93.0 % P=0.383 Number at risk baseline 1MFU 6MFU 12MFU 24MFU PTA 44 44 43 41 36 Viabahn 39 38 37 33 25 P=0.316 FMRP 2015 17

The RELINE Trial : 1 2 yr primary patency 1 year 2 year 74.8 % 58.4 % 28.0 % 11.6 % p<0.001 Number at risk baseline 1MFU 6MFU 12MFU 24MFU PTA 44 33 26 11 4 Viabahn 39 37 35 26 16 p<0.001 FMRP 2015 18

The RELINE Trial : 1 2 yr freedom TLR 1 year 2 year 80.0 % 66.3 % 42.0 % 23.0 % p<0.001 Number at risk baseline 1MFU 6MFU 12MFU 24MFU PTA 44 33 28 16 8 Viabahn 39 38 35 27 17 p<0.001 FMRP 2015 19

Conclusion There is some evidence that chemical solutions are valuable in the battle against ISR. The RELINE results prove, even on the longer run, that a mechanical barrier (like the Viabahn stentgraft) is also a promising tool for treatment of in-stent restenosis FMRP 2015 20

LINC 2015, Leipzig A.Z. Sint-Blasius, Dendermonde Marc Bosiers Koen Deloose Joren Callaert Imelda Hospital, Bonheiden Patrick Peeters Jürgen Verbist OLV Hospital, Aalst RELINE-trial : 24 months results with the Viabahn vs PTA for in-stent restenosis Lieven Maene Roel Beelen R.Z. Heilig Hart, Tienen Koen Keirse Bart Joos Koen Deloose, MD FMRP 2015 21