Endovascular Treatment of Atherosclerotic Popliteal Artery Lesions – Balloon Angioplasty versus primary Stenting: A prospective, multi-centre, randomised study ETAP Thomas Zeller, MD Bad Krozingen, Germany On behalf of the ETAP trial investigators

Disclosures Advisory Board: Medtronic-Invatec, W.L. Gore, Angioslide, Medtronic-Ardian, Covidien-ev3 Consulting Fees/Honoraria: Sanofi-Aventis, C.R. Bard, J&J Cordis, Covidien-ev3, Boston Scientific, Straub Medical, Invatec, Biotronik, Pathway Medical, W.L. Gore Research Grants: Cook, Krauth Medical, Pathway Medical, Abbott Vascular, J&J Cordis, Angioslide, Ardian, Biotronik, Invatec, InnoRa, W.L. Gore, Veryan, Covidien-ev3, Medtronic-Ardian, Medtronic- Invatec, 480 Biomedical

ETAP Background The popliteal artery is considered as a “no-stent”- zone due to potential excessive external forces applied to the stent in the popliteal fossa No prospective comparative controlled trials have yet investigated the performance of stents in the popliteal artery to date The ETAP trial is the first in man trial comparing primary stenting using a contemporary nitinol stent device (Lifestent) with the current “gold standard” POBA

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

ETAP Key Features Investigator initiated European prospective, randomized controlled multi-center trial (9 centers) Unrestricted grant by C.R. BARD-Angiomed Independent data management, corelab adjudication Study Design:  1:1 randomization POBA with provisional stenting vs. primary stenting (Lifestent) in popliteal artery disease Patient cohort:  246 patients Patients with chronic PAD RCC 1-4 No restrictions in lesion length

ETAP Study Endpoints Primary Endpoint Restenosis rate at 12 months (duplex PSVR > 2.4) Secondary Endpoints (6,12 & 24 months) Restenosis rate (PSVR > 2.4) Restenosis rate (PSVR > 2.0) Primary patency rate Secondary patency rate Clinically driven TLR rate Change in RCC Walking distance (treadmill) ABI MACE Stent fractur rate at 12 and 24 months (plain X-ray)

ETAP Inclusion Numbers by Study Center Treatment group (as randomized) Total StentPTA N%N%N% Center Bad Krozingen Hamburg Heidelberg Bad Säckingen Leipzig Bern Wien Flensburg Graz Total

ETAP Patient Characteristics All Patients (N=246) Stent (N=119) PTA (N=127) Age (years, range)72 (41-89)72 (42-89)73 (41-89) Male sex (%) Body-mass-Index26±427±426±4 Diabetes mellitus (%) Dyslipidemia (%) Hypertension (%) Current smoker (%) Coronary heart disease (%) Carotid artery disease (%)

ETAP Lesion Location All Patients (N=246) Stent (N=119) PTA (N=127) Popliteal I+II Popliteal II+III Popliteal I+II+III

ETAP Lesion Characteristics Stent N=119 PTA N=127 P Lesion length [mm] 41.3± ± CTO33% (39)33% (42)1.00 Mean diameter stenosis 93±7%92±8%0.87

ETAP 1-year Primary Patency [%] P < 0.05

ETAP Clinical Outcomes at 1-Year Follow-up Stent (N=97) PTA (N=97) P Death4 (3.9%)2 (2.1%)0.68 Major-or Minor Amputation 3 (3%) 1.0 TLR (ITT)15 (15.4%)49 (50.4%) TLR (OT)15 (15.4%)22 (21.4%)0.29 Myocardial infraction1 (1%)0 (0%)1.0 Limb salvage97 (100%) 1.0 Change in ABI0.22 ( ± 0.3)0.24 ( ± 0.4)0.9 Rutherford-Becker class Median change (IQR) -2 (-3 to -1)-2 (-3 to -1) (-3 to -1)

ETAP Event-Free Survival (ITT) ( Death, TLR, MI, amputation) P < (log-rank test)

ETAP Change in RCC at 12 Months

ETAP Absolute Walking Distance P < 0.05

ETAP Interims Analysis 1-Year Stent Fracture Rate (Corelab) Stent fracture [calc.]* Total yesno N%N%N% 12 months *One type I & II stent fracture each

ETAP Summary ETAP is the first controlled trial investigating the performance of POBA and primary stent placement (Lifestent) in the popliteal artery Lifestent placement in the popliteal artery is safe  Corelab adjudicated 1-year fracture rate 3.4% Lifestent placement results in a significant higher primary patency rate as compared to POBA In ITT analysis no significant difference in change of Rutherford categories In ITT significant better improvement of absolute walking distance in the stent cohort