Is Zilver PTX DES the De Facto Stent to Deploy? Krishna Rocha-Singh, MD, FACC, FAHA Chief Scientific Officer Prairie Heart Institution of Illinois St. John’s Hospital Springfield, IL

Krishna Rocha-Singh, MD Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below. Affiliation/Financial Relationship Company Grant/Research Support Consulting Fees/Honoraria Major Stock Shareholder/Equity Royalty Income Ownership/Founder Intellectual Property Rights Other Financial Benefit None Medtronic, Alucent, BSC, Zimmer-BioMet, ROX, CSI, SPNC, SymicBio PQ Bypass, Vatrix, Aneurysm Diagnostics, Inc. Convergence Consulting, LLC Yes VIVA Board Member

Is Zilver PTX DES the De Facto Stent to Deploy? Lecture Goals: Acknowledge the pitfalls of comparing clinical trial/registry using different nitinol stent platforms with varying assessment metrics/timeframes and patient cohorts. Consider the importance of long-term clinical data to assess clinical utility. Appreciate evolving role of DES vs. DCB ± BMS in treating complex SFA lesions in the evolving DCB era

How Good are Bare Metal Nitinol Stents How Good are Bare Metal Nitinol Stents? 999 Patient Level Data Sets in RC 2-4 Claudicants with Atherosclerotic FP Occlusive Disease Alphabetical listing of studies included: COMPLETE SE DURABILITY II RESILIENT STROLL VIBRANT ZILVER PTX BMS Arm Speak to why selected; they were selected b/c

VIVA SFA Nitinol Stent Meta-Analysis: Limitations/Caveats Exploratory analyses of published data full pre-specification not possible since trials well-known and published Variation in definitions Adds variability but may enhance generalizability of lesion length and ABI findings Large sample size helps to offset variability concern Sample size constrained by available data

VIVA SFA Nitinol Stent Meta-Analysis: Limitations/Caveats Selection bias since only studied approved FDA PMS bare metal stents Approvable stents are the target of inference so unsuccessful stents not relevant Selection of cutoffs for lesion length and ABI post-hoc Sensitivity analyses for tertiles/quartiles help assess robustness

VIVA SFA Nitinol Stent Patient Level Meta-Analysis in 999 Patients: Methods Trial specific definitions utilized: Primary patency 2.0 PSVR cutoff for 5 studies, 2.5 for one study Intervention = patency failure for 5 of 6 studies Target Lesion Revascularization (TLR) Defined as clinically-driven in 5 studies; uncertain in 1 study

Summary of Patient/Lesion Characteristics and Endpoints Overall Summary of Baseline Data and Primary Patency

Lesion Length Association with Patency and CD-TLR at 12-mos Good slide relating patency, lesion length and TLR…was this CD-TLR? UPDATED DATA Patency and TLR Results by Lesion Tertile

DUR II Baseline Lesion Characteristics: Impact of Time on Durability Lesion length (mm) (Normal-to-Normal method)* 109.6 ± 45.0 Lesion length (mm) (20-to-20 method)§ 89.1 ± 44.8 Pre-procedure diameter stenosis (%) 85.8 ± 16.2 Total Occlusion (%) Mean occlusion lesion length (mm)§ 48.1 102.7 Calcification (%) None/Mild 30.0 Moderate 26.8 Severe 43.2

Freedom from Loss of Primary Patency (PSVR < 2.0) at 3 Years 66.1% 77.9% 60.0% 287 Subjects Freedom from loss of primary patency at 3 years was 60.0%

Zilver PTX Drug-Eluting Peripheral Stent Mechanical scaffold: Zilver Flex® Stent Platform Drug therapy: Paclitaxel only 3 µg/mm2 dose density No polymer or binder PTX Coated Uncoated

Zilver PTX Global Clinical Program Zilver PTX RCT Zilver PTX SAS Zilver PTX Japan PMS Key Study Criteria No significant untreated inflow tract stenosis ALL patients treated with Zilver PTX enrolled (up to enrollment limit), NO exclusion criteria At least one patent runoff vessel Maximum 2 Zilver PTX stents per lesion Maximum 4 Zilver PTX stents per patient Lesion length ≤ 14 cm No exclusions One lesion per limb No prior stent in SFA ISR included Excluded if serum creatinine > 2.0, renal failure, or dialysis Antiplatelets Clopidogrel or ticlopidine recommended for 60 days, aspirin indefinitely Follow-up 5 years 2 years Patency DUS core laboratory analysis DUS site analysis Stent Integrity X-ray core laboratory analysis Increasingly complex patients and lesions

Patient Demographics and Comorbidities RCT SAS Japan PMS Patients 236 787 905 Age (years) 68 ± 10 67 ± 10 74 ± 9 Diabetes 50% 36% 59% High cholesterol 76% 58% 61% Hypertension 89% 80% 85% Renal disease1 10% 11% 44% Lesion length (cm) 6.6 ± 3.9 10.0 ± 8.2 14.7 ± 9.7 Total occlusions 33% 38% 42% In-stent restenosis (ISR) 0% 15% 19% Rutherford 4-6 (CLI) 9% 20% 1 Of patients with renal disease in the Japan PMS, 82% were in renal failure (eGFR < 60 and/or dialysis) Increasingly complex patients and lesions

Zilver PTX Primary Patency by DUS Months Primary Patency (n = lesions) RCT (n = 318) SAS (n = 842) Japan PMS (n = 702) 12 84.4% 82.8% 86.4% 24 76.3% N/A 72.3% Primary patency rate is consistent across studies

4-Year Primary Patency (PSVR < 2.0) Zilver PTX in Diabetic Patients 69.3% Non-Diabetics p = 0.50 log-rank 65.9% Diabetics

SUPERB Study Overview Design: Key inclusion criteria Limitations Prospective, single-arm, multicenter Primary safety and effectiveness endpoints compared to VIVA OPG Angiographic core lab: -BIDMC Sonographic core lab: Vascor, Massachusetts General Hospital 264 subjects (ITT); 34 sites; 36 month follow-up Key inclusion criteria Lifestyle limiting claudication or rest pain (Rutherford-Becker 2-4) Resting ABI ≤0.9 Single SFA/proximal popliteal lesion (>60% stenosis or total occlusion); lesion ≥3cm above knee joint Lesion length 40-140mm Limitations Single-arm study Routine duplex imaging only obtained through 12 months

SUPERB: Freedom From TLR Through 3 Years 12 Months 89% 24 Months 84% Freedom From TLR 0% 20% 40% 60% 80% 100% 180 360 540 720 900 1080 36 Months 82% Δ 3 years 7% Time Post Index Procedure (Days)

SUPERB: Outcomes in Severe Calcification Freedom From TLR (K-M) Superb Severe Calcification Subset Severe calcification 45% Patency (VIVA 1 year) 89% Severe Ca++ defined as 1cm both sides vessel

SUPERB: Deployment Technique Impact on Freedom from TLR (±10%) (11-20%) (21-40%) (>40%)

Is Zilver PTX the De Facto DES to Deploy? 5-year follow-up from the Zilver PTX RTC provides important insights regarding long-term outcomes v. BMS Zilver PTX data in more complex anatomies (TASC C & D lesions) and high-risk patient cohorts (DM, CRF, ISR, etc.): Promising >1 year outcomes (TLR, patency) These benefits increase with time – results with Zilver PTX continue to diverge from standard care over 5 years with no late catch-up Questions of cost-effectiveness, particularly in complex anatomies and patient cohorts, of Zilver PTX v. Supera v. DCB ± atherectomy devices awaits further analysis