Fem-Pop Stenting: Is ZILVER PTX DES The “De Facto” Stent to Deploy? IMPLANT Krishna Rocha-Singh, MD Chief Scientific Officer Prairie Heart Institute Saint 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, Zimmer-BioMet, ROX Medical, PQ Bypass Convergence Consulting, LLC Yes VIVA Board Member

Is Zilver PTX DES the De Facto IMPLANT to Deploy? Lecture Goals: Acknowledge the importance of well-designed RCTs/adjudicated registries in specific angiographic cohorts (i.e., long lesions, severely calcified). Consider the importance of long-term clinical data to assess clinical utility of technologies. Review recently released data from the REAL PTX RCT of Zilver PTX DES vs. DCB

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 However, large sample size helps to offset variability concern Sample size constrained by available data (n=999) Rocha-Singh et al, Cath Cardiovasc Interv, In Press

Lesion Length Association with Patency and CD-TLR at 12-mos Patency and TLR Results by Lesion Tertile Good slide relating patency, lesion length and TLR…was this CD-TLR? UPDATED DATA Rocha-Singh et al, Cath Cardiovasc Interv, In Press

Rocha-Singh et al, Cath Cardiovasc Interv, In Press

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 Rocha-Singh et al, Cath Cardiovasc Interv, 2015

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% Rocha-Singh et al, Cath Cardiovasc Interv, 2015

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

Drug-Eluting Technologies: How Do We Target Their Appropriate Use? 3-Yr adjudicated follow-up data in TASC II A-B lesions (mean lesion length 9.5cm, calcium-free) note a 83.5% freedom from CD-TLR rate However, in longer (≥15 cm), calcified lesions (72%) provisional BMS use is required 40% to maintain a 1-yr freedom from CD-TLR of 94% Adjunct use of ‘vessel prep’ devices to reduce provisional stent rates and improve DCB results have be hypothesized.

IN.PACT Global Long Lesion Imaging Cohort: Lesion/Procedural Characteristics Lesions (N) 164 Lesion Type: de novo restenotic (no ISR) ISR 83.2% (134/161) 16.8% (27/161) 0.0% (0/161) Lesion Length 26.40 ± 8.61 cm Total Occlusions 60.4% (99/164) Calcification Severe 71.8% (117/163) 19.6% (32/163) RVD (mm) 4.594 ± 0.819 Diameter Stenosis (pre-treatment) 90.9% ± 14.2 Dissections: 0 37.9% (61/161) A-C 47.2% (76/161) D-F 14.9% (24/161) Device Success [1] 99.5% (442/444) Procedure Success [2] 99.4% (155/156) Clinical Success [3] Pre-dilatation 89.8% (141/157) Post-dilatation 39.1% (61/156) Provisional Stent LL 15-25 cm: LL > 25 cm: 40.4% (63/156) 33.3% (33/99) 52.6% (30/57) Given the provisional BMS use in complex SFA lesion morphologies, should primary DES deployment be considered the primary ‘de facto’ strategy? Device success: successful delivery, inflation, deflation and retrieval of the intact study balloon device without burst below the RBP Procedure success: residual stenosis of ≤ 50% (non-stented subjects) or ≤ 30% (stented subjects) by core lab (if core lab was not available then the site reported estimate was used) Clinical success: procedural success without procedural complications (death, major target limb amputation, thrombosis of the target lesion, or TVR) prior to discharge M. Jaff VIVA 2016

REAL PTX Study Design A Pilot Study Prospective, multicenter (5 EU sites), randomized, controlled trial Zilver PTX DES vs DCB (~90% In.PACT Admiral) (1:1) in native FP disease N= 150 patients, 75 in each group Stratification for lesion length for both groups (1:1:1) short: ≤ 10 cm middle: > 10 and ≤ 20 cm long: > 20 and ≤ 30 cm Mean lesion length: 15.3 ± 8.8 cm Independent angio and DUS core lab adjudication D. Scheinert, LINC 2017

Study Design Follow-up: 3-Years Endpoints: - Primary: Primary Patency @ 12 Month (Duplex) - Secondary: Procedural sucess Major Adverse Event (Major Amputation; Death or TLR within 30 days) Primary Patency @ 24, 36 Month Clinically-driven target lesion revascularization (TLR) ABI, Improvement in Rutherford Categories, Walking capacity (WIQ) D. Scheinert, LINC 2017

Randomized and stratified (n=150) Patient Flow Chart Randomized and stratified (n=150) DCB (n=75)   DES (n=75) Short (n=25) Mid (n=26) Long (n=24) Mid (n=24) Long (n=26) death = 5, withdrawal = 2, missed visit = 1 6 MFU (n=132) 12 MFU (n=122) 24 MFU(n=113) withdrawal =2, lost = 1, missed visit= 3 withdrawal =3 death = 3, withdrawal = 4, lost = 2 death = 2, withdrawal = 6, lost = 1, missed visit = 1    withdrawal = 5, lost = 1  Was any pt randomised to DEB excluded, due to bad PTA??? D. Scheinert, LINC 2017

Lesion Characteristics DCB (n=75) ZilverPTX (n=75) *p-value Claudication (RC 2-3), n (%) 67 (89.3) 63 (84.0) Critical limb ischemia (RC 4-5), n (%) 8 (10.7) 12 (16.0) 0.472 Target lesion length (mm) ± SD* 144.8 ± 92.1 159.6 ± 97.3 0.341 Lesion location, n (%)*** SFA 60 (80.0) Popliteal affected 15 (20.0) 0.524 Occlusion, n (%)*** 40 (53.3) 39 (52.0) 0.870 MLD in lesion, mm ± SD 0.57 ± 0.77 0.66 ± 0.77 0.571** Percent diameter stenosis, % 87.4 ± 16.8 86.9 ± 15.2 0.745** Lesion calcification, n (%) 0.561 None 19 (25.3) 16 (21.3) Mild 22 (29.3) Moderate 2 (2.7) 4 (5.3) Moderately severe 17 (22.7) Severe 26 (34.6) No mention on the 50% severe calcification on other slides – consider adding to slide 17 *Fisher‘s exact test is performed in general, ** non-parametric test (Mann-Whitney-Wilcoxon-U using t approximation) *** Satterthwaite approximation should be generally used (no deviations in all other variables) D. Scheinert, LINC 2017

Acute Outcome D. Scheinert, LINC 2017 DCB (n=75) ZilverPTX *p-value Provisional stenting Core Lab, n (%) 19(25.3) NA Residual Stenosis: Visual estimate ≥ 30%, n (%) 2 (2.7) 1 (1,3) Core Lab > 30%, n (%) 14 (18.7) 30 (40.0) < 0.001* MLD post-procedure, mean ± SD 3.5 ± 0.7 4.1 ± 0.7 < 0.001 Dissection, n (%) 54 (72.0) 29 (38.7) Type A/B, n (%) 19 (25.3) 11 (14.7) Type C-F, n (%) 35 (46.7) 18 (24.0) Complication Embolic event, n (%) 4 (5.3) 1 (1.3) AV-Fistel (local), n (%) 6 (8.0) Target Vessel Perforation, n (%) * For comparison Fisher‘s exact test is performed in general D. Scheinert, LINC 2017

1° Patency @ 12 and 24 months Primary Patency D. Scheinert, LINC 2017 Pt @ risk (n) DCB (75) 64 48 29 DES (75) 63 33 1° Patency (%) DCB 87.6 1.00 76.2 0.96 49.4 0.78 DES 58.2 D. Scheinert, LINC 2017

Significant Loss of 1° Patency in Lesions >20 cm Drug Coated Ballon (ITT) Zilver PTX Primary Patency Consider adding arrows on both- see next slide. Stratified 1° patency @ 24 Month (%) 1 <= 10cm 76.1 2 > 10cm and <= 20cm 40.0 3 > 20 cm and <= 30cm 33.1 Stratified 1° patency @ 24 Month (%) 1 <= 10cm 78.4 2 > 10cm and <= 20cm 56.7 3 > 20 cm and <= 30cm 43.2 * p was calculated using log rank test D. Scheinert, LINC 2017

Residual Stenosis ≥ 30% Acute Outcome DCB (n=75) ZilverPTX *p-value Residual Stenosis Visual estimate ≥ 30%, n (%) 2 (2.7) 1 (1.3) Core Lab > 30%, n (%) 14 (18.7) 30 (40.0) < 0.001* Optimize acute outcome with consistent vessel preparation  may potentially lead to better long-term patency Consider adding; emerging evidence suggests this will influence longer term patency Vessel prep is a big thing for LINC 2017-- D. Scheinert, LINC 2017

Fem-Pop Stenting: Is ZILVER PTX DES The “De Facto” Stent to Deploy? REAL PTX randomized controlled pilot trial results illustrates several points: --- All RCTs are not created equal --- “Vessel prep” and uniform deployments techniques both DCBs and Zilver PTX are essential --- Additional analysis of the ‘mode of failure’ should provide additional insights --- Cost considerations in technology choice must be assessed in future trials