Wires, balloons, drug-eluting devices, ect. NEW TECHNOLOGIES: Wires, balloons, drug-eluting devices, ect. Fabrizio Fanelli Vascular & Interventional Radiology Unit Department of Radiological Sciences “Sapienza” – University of Rome

Below The Knee Arteries Small vessels Long lesions Occlusions > stenoses More vessels Calcifications L. Graziani – Eur J Vasc Endovasc Surg 2007

CLI : Mean Length Treated lesions 5% ATG 63±61 mm 55% FEM-POP 116±113 mm 185±121 mm 96% BTK R.Ferraresi - oral presentation CICE 2012

PTA F.U. PATENCY TLR DEBATE 1 12 mos 28.0% 24.0% Leipzig Registry2 31.0 % 50.0% DEBELLUM 3 47.1% 47.0% BMS F.U. PATENCY TLR ACHILLES4 12 mos 57.1% 16.0% DESTINY5 54.3 % 33.6% YUKON6 55.6% 13.0% 1) F. Liistro - oral presentation TCT 2012 4) K. Katsanos - oral presentation CIRSE 2011 2) A. Schmidt – JACC 2011 3) F. Fanelli - oral presentation CIRSE 2012 5) M. Bosiers – J Vasc Surg 2012 6) A. Rastan – European Heart Journal 2011

…. New Technologies ….

Micro-puncture set Guidewires Micro-guidewires Introducers Support catheters Low profile balloon catheters Atherectomy devices Drug eluting balloons (DEB) Bare metal stents Drug eluting stents (DES)

Micro-puncture set Guidewires Micro-guidewires Introducers Support catheters Low profile balloon catheters Atherectomy devices Drug eluting balloons (DEB) Bare metal stents Drug eluting stents (DES)

Drug Eluting Balloons In.Pact Amphirion – Medtronic /Invatec Advance LP 18 PTX – Cook Freeway II/Dior – Eurocor Elutax – Aachen Medical

real world BTK complex lesions DEB BTK Leipzig Registry Study type Prospective single center, single arm, investigator initiated study Objective Assess IN.PACT Amphirion™ efficacy for the treatment of long BTK lesions occlusions Population Symptomatic patients with CLI or severe claudication Eligibility At least one lesion BTK ≥ 80 mm Prim. Endpoint 3 month restenosis rate Nr of patients 104 / 109 limbs IN.PACT™ Amphirion in real world BTK complex lesions A. Schmidt – JACC 2011

DEB BTK Leipzig Registry vs historical PTA cohort (A.Schmidt - Cath. and Cardiovasc. Interventions 2010) DEB BTK Leipzig Registry DEB (angio subgroup) PTA (historical group) # patients / limbs 74 / 79 58 / 62 Male gender 51 (68.9%) 38 (65.5%) mean age (y) 73.5 ± 9.3 70.5 ± 8.08 diabetics 54 (73%) 52 (89.7%) Renal insuff. 34 (45.9%) 30 (51.7%) RC 3 16 (20.3%) 0 (0%) RC 4 14 (17.7%) 16 (25.8%) RC 5 49 (62%) 46 (74.2%) RC 6 avg lesion length 173 ± 87 mm 183 ± 75 mm Tot occlusions 61.9% 64.9% DEB (angio subgroup) PTA (historical group) 3m Ang. FU Restenosis (>50%) 27.4% 69% Full-segment Resten. 10% 56% Restenosis Length 64 mm 155 mm 12m Clinical FU 15m Clinical FU Deaths 16.3% 10.5% Limb Salvage 95.6% 100% Clinical Improvement (1) 91.2% 76.5% Compl. wound healing 74.2% 78.6% TLR 17.3% 50% (1) clinical improvement = reduction in size and/or depth of ulceration or improvement of rest-pain

DEB BTK Leipzig Registry vs historical PTA cohort (A.Schmidt - Cath. and Cardiovasc. Interventions 2010) DEB BTK Leipzig Registry DEB (angio subgroup) PTA (historical group) # patients / limbs 74 / 79 58 / 62 Male gender 51 (68.9%) 38 (65.5%) mean age (y) 73.5 ± 9.3 70.5 ± 8.08 diabetics 54 (73%) 52 (89.7%) Renal insuff. 34 (45.9%) 30 (51.7%) RC 3 16 (20.3%) 0 (0%) RC 4 14 (17.7%) 16 (25.8%) RC 5 49 (62%) 46 (74.2%) RC 6 avg lesion length 173 ± 87 mm 183 ± 75 mm Tot occlusions 61.9% 64.9% DEB (angio subgroup) PTA (historical group) 3m Ang. FU Restenosis (>50%) 27.4% 69% Full-segment Resten. 10% 56% Restenosis Length 64 mm 155 mm 12m Clinical FU 15m Clinical FU Deaths 16.3% 10.5% Limb Salvage 95.6% 100% Clinical Improvement (1) 91.2% 76.5% Compl. wound healing 74.2% 78.6% TLR 17.3% 50% (1) clinical improvement = reduction in size and/or depth of ulceration or improvement of rest-pain

DEBATE BTK Investigator initiated, single center Study Randomized (1:1) DEB vs. standard PTA Primary Endpoint: 12-month Angiographic Binary (>50%) Restenosis Rate Secondary Endpoints: TLR and Reocclusion CLI + Diabetes 150 (Tibial) Lesions Random (1:1) DEB (75 lesions) Std PTA (75 lesions) Key Inclusions RC 4-5-6 and Diabetes Stenosis / occlusions >40 mm in at least 1 tibial vessel with distal run-off Key Exclusions Allergy to Paclitaxel Contraindication for combined antiplatelet treatment Life expectancy <1 year Aspirin + Clopidogrel (1 month) 12-month Angiographic and Clinical follow-up 24-month Duplex and Clinical follow-up F. Liistro - oral presentation TCT 2012

DEB PTA p Patients 65 67 / Age 74±9.4 75±9.6 0.7 Smoke 13 (20%) 7 (10.4%) 0.1 Hypertension 46 (70.8%) 52 (77.6%) 0.4 Hypercholesterolemia 23 (35.4%) 16 (23.9%) Diabetes 65 (100%) 67 (100%) 1 Obesity 23 (35.3%) 26 (38.8%) 0.5 Dialysis 7 (10.8%) Coronary artery disease 12 (18.5%) 10 (14.9%) 0.6 Limbs 71 72 0.9 Texas wound ulcer class. I C 1 (1.4%) 3 (4.2%) II C 5 (6.9%) I D 7 (9.9%) 9 (12.5%) II D 34 (47.9%) 32 (44.4%) III D 26 (36.6%) 23 (31.9%)

DEBELLUM Drug Eluting Balloon Evaluation for Lower Limb mUltilevel treatMent Investigator initiated, single center Study Randomized (1:1) DEB vs. standard PTA Primary Endpoint: 6-month LLL Secondary Endpoints: TLR, Primary Patency, Fontaine change, MAE at 6 and 12 months Key Inclusions Fontaine Stage IIb, III, IV SFA, popliteal and BTK lesions either isolated or concomitant De-novo lesions Stenosis or occlusions 3 - 30 cm F. Fanelli - oral presentation CIRSE 2012

12-mos TLR analysis per lesion

DEBELLUM - 12 mos F.U. DEB PTA Angio 6 mos Angio 12 mos Restenosis rate 15.3% (2 lesions) 41.1% (7 lesions) 23.07% (3 lesions) 52.9% (9 lesions) TLR 7.69% (1 lesion) 23.5% (4 lesions) 47.0% (8 lesions) Occlusion rate 9.1% Death Major amputation 10% (1 patient) 9.09% 9.09% (1 patient) Minor amputation 18.8% (2 patients) 18.8% (2 patients)

Prospective Randomized Multicenter Trial 50 pts. RC: 4-6 >50% calcified stenosis popliteal, tibial and peroneal aa.

OA + PTA PTA p Stenting 6.9 % 14.3 % 0.44 Dissection 6 pts 1 pts ns Perforation / 1 Distal Embolization Max Inflation Press <0.001 2 - 4 59.3 % 11.8 % 5 - 6 14.8 % 8.8 % 7 - 8 7.4 % 26.5 % 9 - 10 32.4 % 11 - 12 >12 11.1 % Mean 5.9 ± 4.2 9.4 ± 3.8

OA + PTA PTA p Stenting 6.9 % 14.3 % 0.44 Dissection 6 pts 1 pts ns Perforation / 1 Distal Embolization Max Inflation Press <0.001 2 - 4 59.3 % 11.8 % 5 - 6 14.8 % 8.8 % 7 - 8 7.4 % 26.5 % 9 - 10 32.4 % 11 - 12 >12 11.1 % Mean 5.9 ± 4.2 9.4 ± 3.8

Secondary Endpoints

DEB F.U. PATENCY TLR DEBATE 1 12 mos 71.0% 13.0% Leipzig Registry2 72.6 % 17.3% DEBELLUM 3 76.9% 15.3% PTA F.U. PATENCY TLR DEBATE 1 12 mos 28.0% 24.0% Leipzig Registry2 3 mos 31.0 % 50.0% DEBELLUM 3 47.1% 47.0% 1) F. Liistro - oral presentation TCT 2012 3) F. Fanelli - oral presentation CIRSE 2012 2) A. Schmidt – JACC 2011

What about Stent … ?

DEB F.U. PATENCY TLR DEBATE 1 12 mos 71.0% 13.0% Leipzig Registry2 72.6 % 17.3% DEBELLUM 3 76.9% 15.3% BMS F.U. PATENCY TLR ACHILLES4 12 mos 57.1% 16.0% DESTINY5 54.3 % 33.6% YUKON6 55.6% 13.0% 1) F. Liistro - oral presentation TCT 2012 4) K. Katsanos - oral presentation CIRSE 2011 2) A. Schmidt – JACC 2011 3) F. Fanelli - oral presentation CIRSE 2012 5) M. Bosiers – J Vasc Surg 2012 6) A. Rastan – European Heart Journal 2011

DEB F.U. PATENCY TLR DEBATE 1 12 mos 71.0% 13.0% Leipzig Registry2 72.6 % 17.3% DEBELLUM 3 76.9% 15.3% DES F.U. PATENCY TLR ACHILLES4 12 mos 75.0% 10.0% DESTINY5 85.2 % 8.7% YUKON6 80.6% 13.8% 1) F. Liistro - oral presentation TCT 2012 4) K. Katsanos - oral presentation CIRSE 2011 2) A. Schmidt – JACC 2011 3) F. Fanelli - oral presentation CIRSE 2012 5) M. Bosiers – J Vasc Surg 2012 6) A. Rastan – European Heart Journal 2011

Everolimus-eluting stent vs. bare metal stent JVIR 2009; 20(9):1141-1150 Everolimus-eluting stent vs. bare metal stent 103 pts. CLI Angioplasty + Bailout stenting

HR: 4.8, CI 2.9-7.9 p<0.001 HR: 2.5, CI 1.3-5.0 p=0.006 D. Siablis – JVIR 2009; 20(9):1141-1150

Xcience-Prime Xcience-Prime

Conclusions DEB patency rate similar to DES but with the advantage of “nothing left behind”. Efficacy of DEB in very calcified arteries still under evaluation Combined treatment with atherectomy must be validated.

The Future … Bioabsorbable Stent Adaption to flexion, extension •Overcome Stent fractures •Positive Remodelling •Might act as a transporter (Gen-Therapy) •Surgeon’s friend

ABSORB Study Poly-L-lactide + Everolimus 30 pts. 5-y F.U. - No cardiac death - No thrombosis - MACE: 3.4 % - LLL 0.27 mm

fabrizio.fanelli@uniroma1.it