The 4EVER Trial Final 24 month results: BEC 2014, София The 4EVER Trial Final 24 month results: A.Z. Sint-Blasius, Dendermonde Marc Bosiers Koen Deloose Joren Callaert Imelda Hospital, Bonheiden Patrick Peeters Jürgen Verbist OLV Hospital, Aalst Lieven Maene R.Z. Heilig Hart, Tienen Koen Deloose, MD Koen Keirse

Point to make….. “Less invasive 4F devices, with sufficient chronic outward forces & high crush resistance and radial resistive forces, show equal technical success, primary patency and freedom from TLR rates as 6F devices, also on the longer term, and without the need for expensive closure devices”

4EVER Trial outline Physician-Initiated, prospective, non-randomized, multi-center Trial Investigating the Safety of the Full 4F EndoVascular TrEatement AppRoach of Infra-Inguinal Arterial Stenotic Disease

Less invasive 4F devices… Fortress 4F 45/100cm Biotronik Cruiser 18 Biotronik CXI support catheter (Cook) Pulsar 18 Biotronik Passeo 18 Biotronik

Less invasive 4F devices… Low Profile Delivery Systems Puncture hole size mm 4.52 mm² 44.44 % 7.07 mm² 69.44 % 10.18 mm² 100.00 % 2 1.8 1.5 1.2 1 6F 5F 4F

…with sufficient chronic outward force… Outward force exerted on vessel by self expanding stents to achieve preset diameter Stent Preset Diameter Vessel Wall Zhao HQ, Nikanorov A, Virmani R, Jones R, Pacheco E, Schwartz LB. Late stent expansion and neointimal proliferation of oversized Nitinol stents in peripheral arteries. Cardiovasc Intervent Radiol. 2009 Jul;32(4):720-6. Stent Placement COF Stent COF

…with sufficient chronic outward force… TOO LOW… 4EVER : calcified lesions = 31% 4EVER : Technical success rate = 100% “the ability to cross and stent the lesion in order to achieve residual angiographic stenosis no greater than 30% and residual stenosis less than 50% by duplex imaging” Impossible to open the lesion Residual stenosis

…with sufficient chronic outward force… TOO HIGH… chronic stent-vessel irritation intimal hyperplasia

…with sufficient chronic outward force… Average reference vessel diameter of SFA is 5 mm Most commonly used stent diameter in SFA is 7 mm 1 1- Garcia L. Superb Trial 12 Month Results. Presented at TCT 2012. Miami, FL.

…with sufficient chronic outward force…

…with sufficient chronic outward force… Even when oversizing low rates of COF, due to the flat expansion curve

…with sufficient chronic outward force… Bent Leg:vessel diameter range: 5.02 - 2.98 mm : 6mm stent A implant 100N Expansion force increases with decreasing diameter 60N 40N 5,02 Flat expansion force 2,98 5,02 Illustration is artist’s rendition.

…with sufficient chronic outward force… Bent Leg:vessel diameter range: 5.02 - 2.98 mm : 6mm stent B implant Flat expansion force curves induce lower COF & offer less concern for precise vessel sizing Expansion force increases with decreasing diameter 40N 5,02 30N 20N Flat expansion force 2,98 5,02 Illustration is artist’s rendition.

…with high radial resistive force… Resistive force exerted by self expanding stents to resist CONCENTRIC squeezing by the artery (concentric restenosis) or other external factors Vessel Wall Stent RRF Stent Placement Zhao HQ, Nikanorov A, Virmani R, Jones R, Pacheco E, Schwartz LB. Late stent expansion and neointimal proliferation of oversized Nitinol stents in peripheral arteries. Cardiovasc Intervent Radiol. 2009 Jul;32(4):720-6. Stent RRF

…with high radial resistive force…

…with high radial resistive force…

…with high radial resistive force… Flat RRF curve with low variations according to diameter changes

…with high crush resistance… Crush resistance exerted by self expanding stents to resist ECCENTRIC, focal compression of the artery (external finger pinching or eccentric restenosis) circular ovalized Unloaded Loaded

…with high crush resistance… At 10, 25 and 50% radial compression, the pulsar stent has similar RRF to other devices 50% 25% 10%

…show in equal circumstances as 6F device-studies… Patient demographics (N=120) Male (%) 82 (68.34) Age (min – max; SD) 71 (47 – 90; 9.70) Nicotine abuse (%) 50 (41.67) Hypertension (%) 79 (65.83) Diabetes mellitus (%) 43 (35.84) Renal insufficiency (%) 13 (10.83) Hypercholesterolemia (%) 66 (55.00) Obesity (%) 39 (32.50) Rutherford category 2 43 (35.83%) Rutherford category 3 57 (47.50%) Rutherford category 4 20 (16.67%)

…show in equal circumstances as 6F device-studies… Lesion characteristics (N=120) Left/Right limb (%) 71 (59.17%) /49 (40.83%) Lesion length in mm (min – max) 72.1 (10 – 200) Popliteal involvement (%) 5 (4.17%) Occlusions (%) 25 (20.83%) Ulcerated lesion (%) 3 (2.50%) Calcified lesion (%) 37 (30.83%) Presence of trombus (%) 2 (1.67%)

…show in equal circumstances as 6F device-studies… Study name Device Mean Lesion Length Resilient Lifestent 6.2 cm Zilver Flex arm Zilver Flex 6.3 cm Zilver PTX arm Zilver PTX 6.6 cm Durability II Everflex 8.9 cm Supera 9.0 cm Durability 9.6 cm Absolute Vienna Absolute 10.1 cm 4EVER Pulsar 18 7.2 cm

…equal clinical success as 6F devices…

…equal primary patency rates as 6F devices… At 2 years… 81.4% 72.3 % time baseline at risk 120 % 100% 24MFU 63 72.3%

…equal primary patency rates as 6F devices… At 2 years… 82.0% 80.2% 76.7 % P=0.485 66.8% time baseline Calcification 37 No calcification 83 24MFU 27 62

…equal freedom from TLR rates as 6F devices… At 2 years… 89.3% 82.7 % time baseline at risk 120 % 100% 24MFU 71 82.7%

…equal freedom from TLR rates as 6F devices… At 2 years… 91.1% 85,1% P = 0.0892 85.2% 82,3% baseline 1MFU 6MFU 12MFU 24MFU # 70 69 67 61 46 % 100 98,6 94,1 82,3 43 38 33 23 92,7 87,8 85,1

Loss of primary patency in combination with stent fracture: Fracture rate at 12-months Stent fracture rate: 4.17% (5/120) # Loss PP Class 0 No strut fractures 115 Class I Single tine fracture 1 Class II Multiple tine fractures Class III Stent fracture(s) with preserved alignment of the components 3 Class IV Stent fracture(s) with mal-alignment of the components Class V Stent fracture(s) in a trans-axial spiral configuration Loss of primary patency in combination with stent fracture: 1.67% (2/120)

…without the use of expensive closure devices. No closure devices were used Decreased manual compression time : 8.2 min BOGART, Am J Crit Care, 1995 – 6F – 22 min SIMON, Am J Crit Care, 1998 – 6F – 14.9 min UPPONI, Eur J Radiol. 2007 – 6F – 10.6 min

…without the use of expensive closure devices. Number of puncture site complications (secondary endpoint) = 3.33 % major hematomas No surgical repair – 3 transfusions 17.65% in Coumarin patients 0.97% in non Coumarin patients p = 0.0048

Point made….. “Less invasive 4F devices, with the right chronic outward force, radial resistive force and crush resistance, show equal technical success, primary patency and freedom from TLR rates as 6F devices, also on the longer term, and without the need for expensive closure devices”