Are Drug Eluting Stents the Future of SFA Treatment? Sahil A. - PowerPoint PPT Presentation

SCAI 2019 May 22, 2019 Are Drug Eluting Stents the Future of SFA Treatment? Sahil A. Parikh, MD, FACC, FSCAI Associate Professor of Medicine Director, Endovascular Services Center for Interventional Vascular Therapy New York-Presbyterian Hospital Columbia University Irving Medical Center Columbia University Vagelos College of Physicians and Surgeons

Disclosures 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 • TriReme Medical, Shockwave Medical, • Grant/Research Support NIH, Surmodics, Silk Road Medical (CEC); Boston Scientific (DSMB) • Consulting Fees/Honoraria • Terumo, Abiomed • Abbott, Boston Scientific, Medtronic, CSI, • Advisory Board Philips

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Dosing Considerations Balancing Safety and Efficacy TOXIC EFFECT 100 Arterial Paclitaxel Concentration Typical DCB IMPROVE EFFICACY Curve THERAPEUTIC (overlap restenotic cascade) WINDOW (ng/mg) 5 Typical DES Curve NO EFFECT 1 REDUCE COMPLICATIONS 0 0 25 50 75 100 Time (Days)

SCAI AUC and FP PVI: 2017 Update Klein AJ et al. Catheter Cardiovasc Interv. 2017;90(4):E90-E110.

SCAI Consensus Guidelines for Device Selection in FP PVI Device Selection as DEFINITIVE Therapy Feldman DN et al. Catheter Cardiovasc Interv 2018.

ACC/AHA AUC DES and DCB are both APPROPRIATE for SFA lesions of any length

5-year Primary Patency (PSVR < 2.0) Zilver PTX vs. Standard Care 66 66.4% .4% Zilver PTX p < 0.01 log-rank Optimal PTA 43 43.4% .4% + BMS At 5 years, Zilver PTX demonstrates a 41% reduction in restenosis compared to standard care Source: Dake M. The Zilver PTX randomized trial of paclitaxel-eluting stents for femoropopliteal artery disease: 5-year results. Presented at: VIVA 2014: Vascular Interventional Advances Conference; November 4-7, 2014; Las Vegas, Nevada.

Zephyr Registry: Real World Support for Zilver PTX and Predictors of Restenosis 1. LENGTH >160MM 2. MLA <12mm2 3. EEM area <27mm2 Lida, et al. JACC: CI Volume 8, Issue 8, July 2015, Pages 1105 – 1112

Patient Flow 852 screened 328 ineligible 61 general inclusion/exclusion criteria 59 in sub-studies (Eluvia only) 267 angiographic criteria Randomized Trial 465 randomly assigned (2:1) 309 assigned to Eluvia 156 assigned to Zilver PTX 4 withdrew consent 9 withdrew consent 6 died 6 died PI-549902-AE Apr2019 146 in full cohort analysis at 12 months 294 in full cohort analysis at 12 months 142 clinical visit follow up at 12 months 282 clinical visit follow up at 12 months Gray WA, Lancet 2018.

Baseline Patient Characteristics Eluvia (N=309) Zilver PTX (N=156) Age (years) 68.5 ± 9.5 67.8 ± 9.4 Male 66.0% 66.7% Smoking status Current 35.3% 40.4% Previous 50.8% 43.6% Diabetes Mellitus 41.7% 43.6% Hyperlipidaemia 76.3% 75.6% Hypertension 82.2% 85.3% Coronary Artery Disease 50.8% 45.2% Renal Insufficiency 8.1% 7.1% PI-549902-AE Apr2019 Gray WA, Lancet 2018.

Baseline Lesion Characteristics Eluvia (N=309) Zilver PTX (N=156) Arterial Segments Ostial 1.6% 0.6% Proximal SFA 12.9% 10.3% Mid SFA 65.0% 66.7% Distal 66.3% 65.4% Proximal Popliteal Artery 18.0% 12.7% Lesion length (mm) 86.5 ± 36.9 81.8 ± 37.3 Calcification None/Mild 36.5% 32.3% Moderate 22.8% 34.8% Severe 40.1% 32.3% 5.0 ± 0.8 5.1 ± 0.8 Reference Vessel Diameter (mm) % Diameter Stenosis 80.7% ± 16.5% 80.8% ±16.4% PI-549902-AE Apr2019 <50% 1.6% 1.9% 50%-<100% 67.2% 67.7% 100% (Occlusion) 31.2% 30.3% Gray WA, Lancet 2018. Angiographic Core Laboratory Data

Effectiveness I Primary Patency at 12 Months Treatment Difference for Primary Patency Δ Eluvia Zilver PTX p value (N=309) (N=156) (95% CI) 86.8% 77.5% 9.3% 0.0144 (243/280) (110/142) (1.4%, 17.3%) Superior primary patency for Eluvia vs Zilver PTX PI-549902-AE Apr2019 IMPERIAL Trial: A global randomized controlled multi- center trial with 2:1 randomization of the Eluvia™ Drug - Eluting Stent against Cook Medical’s Zilver ™ PTX™ Stent, single -blind, non-inferiority design; independent core lab adjudication. Superiority determined in a post hoc analysis that was specified prior to unblinding. 12-Month Primary Patency rate of 86.8% in the Eluvia arm vs. 77.5% in the Zilver PTX arm (p-value = 0.0144). Primary patency defined as duplex ultrasound PSVR ≤2.4, in the absence of clinically -driven target Gray WA, Lancet 2018. lesion revascularization or bypass of the target lesion, as assessed by the DUS core lab.

Effectiveness I Primary Patency at 12 Months Kaplan-Meier Analysis of Primary Patency PI-549902-AE Apr2019 0 1 2 3 4 5 6 7 8 9 10 11 12 13 Error bars are 95%CI. Primary patency defined as duplex ultrasound PSVR ≤2.4, in the absence of clinically -driven target Gray WA, Lancet 2018. lesion revascularization or bypass of the target lesion, as assessed by the DUS core lab.

Safety • Non-inferior MAE rate for Eluvia vs Zilver PTX • Eluvia CD-TLR and stent thrombosis rates ~50% less than Zilver PTX • 6 cases of positive remodeling in Eluvia arm (2.1%) All 6 lesions patent at 1 year – None had TLR or stent thrombosis – Eluvia Zilver PTX (N=309) (N=156) Difference 95%CI p value MAE 4.9% 9.0% -4.1% -9.4%,1.2% 0.0975 Any death at 1 month 0.0% 0.0% 0 NA NA Target limb major 0.3% 0.0% 0.3% -0.3%, 1.0% 1.0000 amputation PI-549902-AE Apr2019 Clinically-driven TLR 4.5% 9.0% -4.4% -9.7%, 0.8% 0.0672 Stent Thrombosis 1.7% 4.0% -2.3% -5.8%, 1.2% 0.1956 0.3% -0.3%, 0.9% 0.4315 Stent Fractures 0.3% 0.0% Clinical Events Committee-adjudicated adverse events included MAE and stent thrombosis. Potential stent fractures were identified by radiography and verified by the angiographic core lab. Stent-based fracture rate calculation based on 319 implanted Eluvia and 197 Zilver PTX stents. MAE, major adverse events; CD-TLR, clinically-driven target lesion revascularization. Gray WA, Lancet 2018.

IMPERIAL Summary of Deaths: RCT (2:1 randomization) CEC-Adjudicated Cause of Death* 1-year Rate Eluvia Zilver PTX All 2.0% (6/301) 3.9% (6/152) Cardiac 1.0% (3/301) 3.3% (5/152) Vascular 0.0% (0/301) 0.7% (1/152) Non-Cardiovascular 1.0% (3/301) 0.0% (0/152) Days from Index Device Type Site-Reported Cause of Death CEC Adjudication* Procedure Eluvia Cardiac arrest Cardiac 89 Eluvia Unknown cause of death Cardiac 195 Eluvia Congestive heart failure diastolic dysfunction acute on chronic Cardiac 275 Eluvia Multi organ failure Non-cardiovascular 140 Eluvia Giant cell B-cell non-Hodgkin lymphoma Non-cardiovascular 192 Eluvia Respiratory insufficiency type 1 Non-cardiovascular 329 PI-549902-AE Apr2019 Zilver PTX Worsening heart failure Cardiac 31 Zilver PTX Cardiac arrest Cardiac 78 Zilver PTX Unknown cause of death Cardiac 171 Zilver PTX Cardiopulmonary failure Cardiac 327 Zilver PTX Coronary heart disease Cardiac 353 Zilver PTX Intra-cerebral haemorrhage Vascular 271 CEC, Clinical Events Committee. *The CEC considered all deaths cardiac unless an unequivocal non-cardiac cause could be established. Gray, WA LINC 2019

IMPERIAL Diabetic Cohort I Primary Patency at 12 Months 180 patients had medically-treated diabetes Kaplan-Meier Estimate (116 Eluvia & 64 Zilver PTX) 100% Primary Patency Rate (%) 80% 87.4% 60% 40% 80.2% Month 20% At risk: 6 9 12 13 Eluvia 56 54 42 24.5 Zilver PTX 28 24.5 17 8.5 0% Log-rank p= 0.2905 0 1 2 3 4 5 6 7 8 9 10 11 12 13 PI-549902-AE Apr2019 Months Since Procedure Observed Rate: 84.6% (88/104) Eluvia vs 79.3% (46/58) Zilver PTX Primary patency defined as duplex ultrasound PSVR ≤2.4, in the absence of clinically -driven target lesion revascularization or bypass of the target lesion, as assessed by the DUS core lab. Müller-Hülsbeck S, LINC 2019

IMPERIAL Eluvia Baseline CTO I Primary Patency at 12 Months 100% Primary Patency Rate (%) 80% 90.6% 60% Non-CTO 83.9% 40% CTO 20% Log-rank p= 0.0762 0% 0 1 2 3 4 5 6 7 8 9 10 11 12 13 PI-549902-AE Apr2019 Months Since Procedure Kaplan- Meier estimate. Primary patency defined as duplex ultrasound PSVR ≤2.4, in the absence of clinically - Vermassen, F. CX 2019. driven target lesion revascularization or bypass of the target lesion, as assessed by the DUS core lab.

IMPERIAL Eluvia Calcified Lesions I Primary Patency at 12 Months 100% Primary Patency Rate (%) 80% 89.2% 60% Moderate/Severe 87.0% 40% None/Mild 20% 0% Log-rank p= 0.569 PI-549902-AE Apr2019 0 1 2 3 4 5 6 7 8 9 10 11 12 13 Months Since Procedure Kaplan- Meier estimate. Primary patency defined as duplex ultrasound PSVR ≤2.4, in the absence of clinically - Vermassen, F. CX 2019. driven target lesion revascularization or bypass of the target lesion, as assessed by the DUS core lab.