Division of Endovascular Interventions Mount Sinai Hospital New York 07/25/2018

Presents with 1 Block claudication with Left>>R Case presentation 71 year old female HTN, DM, dyslipidemia,CAD, Ex smoker, known PAD with mutilple PTA’s and R AKA Presents with 1 Block claudication with Left>>R Medications: ASA, plavix, Lipitor, Lisinopril, Imdur, Metoprolol Hb- 10.0, INR- 1.0, Creatinine- 1.4, ABI - Right – 0.77, Left 0.58

RUNOFF LLE

STRATEGY Right CFA access 7F,45 cm crossover sheath Therapeutic anticoagulation- Angiomax IVUS to rule out thrombus (Angioject vs Penumbera) Embo shield Filter Eximer Laser vs Jet Stream vs DA Endograft vs DCB angioplasty vs Zilver PTX

FILTER ALGORITHM Embolic Protection Device Algorithm CTO = chronic total occlusion; ISR = in-stent restenosis; LL = lesion length; PAD = peripheral artery disease. Prakash Krishnan et al. JCIN 2017;10:403-410

Design EXCITE ISR Trial 250 patients enrolled between June 2011 and February 2014 in 40 clinical sites in United States DESIGN: Prospective, randomized, multi-center clinical evaluation of excimer laser atherectomy (ELA) OBJECTIVE: To evaluate safety and efficacy of ELA with adjunctive PTA (ELA+PTA) versus PTA alone for treating femoropopliteal in-stent restenosis PRINCIPAL INVESTIGATORS Eric J Dippel, MD Craig Walker, MD 7 lesions uncrossable 250 lesions crossable by guidewire 169 ELA + PTA 81 PTA Primary Safety endpoint at 37 days (n=155) Primary Safety endpoint at 37 days (n=73) Primary Efficacy endpoint at 212 days (n=117) Primary Efficacy endpoint at 212 days (n=56)

Primary Endpoints Primary Safety Endpoint Major Adverse Events through 30 days: Death Unplanned Major Amputation Target Lesion Revascularization (TLR) Primary Efficacy Endpoint Freedom from clinically driven TLR at 6 months DUS binary restenosis Return of clinical symptoms Deteriorated ABI or Rutherford Classification

Procedural Success ELA+PTA n = 169 PTA n = 81 P Value Turbo Elite use 79.9 na Distal protection 40.2 30.9 0.16 % Diameter Stenosis 23.9±9.3 25.1±10.9 0.24 Residual Stenosis >30% 4.7 13.6 0.02 Procedural Success 93.5 82.7 0.03

Procedural Complications All events adjudicated by CEC This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) 9

Product-Limit Survival Estimates Primary Patency Product-Limit Survival Estimates With number of subjects at risk 365 p < 0.005 Survival Probability Days from Index Procedure

Product-Limit Survival Estimates Freedom from TLR Product-Limit Survival Estimates With number of subjects at risk 365 p < 0.003 Survival Probability Days from Index Procedure

ELA with PTA should be considered for femoropopliteal ISR Conclusions ELA with adjunctive PTA treatment of ISR is superior to PTA alone for the treatment of femoro- popliteal ISR: Complicated lesions averaging 19 cm in length Significantly higher procedural success rate (ELA 93.5% vs PTA alone 82.7%, P=0.02) Significantly higher safety rate (freedom from MAE: ELA 94.2% vs. PTA alone 79.2%, P<0.001) Significantly lower rate of TLR for ELA throughout study ELA with PTA should be considered for femoropopliteal ISR

RELINE TRIAL

RELINE- 1 year outcome Journal of Endovascular Therapy 2015;22:1–10

IN.PACT Global Study: ISR Imaging Cohort Patient and Clinical Characteristics Characteristic IN.PACT™ Admiral™ DCB (n=131 Subjects) Age 67.8y ± 10.1 Male Gender 69.5% (91/131) Diabetes 35.1% (46/131) Insulin Dependent Diabetes 15.3% (20/131) Hypertension 81.5% (106/130) Hyperlipidemia 72.1% (93/129) Current Smoker 35.9% (47/131) Obesity (BMI ≥ 30 kg/m²) 17.6% (23/131) Coronary Heart Disease 36.5% (46/126) Carotid Artery Disease 19.8% (23/116) Renal Insufficiency1 9.9% (11/111) Previous Peripheral Revascularization 100.0% (131/131) Concomitant BTK Disease 43.3% (55/127) ABI 0.667 ± 0.187 (124) Rutherford Category Baseline serum creatinine ≥1.5 mg/dL. Brodmann M, et al JACC CI 2017

IN.PACT Global Study: ISR Imaging Cohort Lesion Characteristics Procedural Characteristics Characteristic IN.PACT DCB (N=149 Lesions) ISR (149/149) Lesion Length (cm) 17.17 ± 10.47 Total Occlusions 34.0% (48/141) Calcification Severe Calcification* 59.1% (78/132) 8.3% (11/132) RVD (mm) 5.222 ± 0.601 Diameter Stenosis (pre-treatment) 84.8% ± 14.9 Dissections None A-C D-F 69.1% (103/149) 26.2% (39/149) 4.7% (7/149) Characteristic IN.PACT DCB (N=131 Subjects) Device Success1 99.6% (282/283) Procedure Success2 99.2% (130/131) Clinical Success3 98.5% (129/131) Pre-dilatation 64.1% (84/131) Post-dilatation 26.0% (34/131) Provisional Stent 14.5% (19/131) Device success defined as successful delivery, inflation, deflation and retrieval of the intact study balloon device without burst below the RBP. Procedure success defined as 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 defined as procedural success without procedural complications (death, major target limb amputation, thrombosis of the target lesion, or TVR) prior to discharge. * Severe calcium definition used by study sites and core laboratory is bilateral calcium at the same location (also measured in sections), ≥ half of the total lesion length, ≥180◦ (both sides of the vessel at the same location). Dattilo, R; J Invasive Cardiol 2014;26(8):355360 Brodmann M, et al JACC CI 2017

IN.PACT Global Study: ISR Imaging Cohort Primary Patency1 through 1 Year 102 Primary patency at 12 months was high at 88.7% and consistent with the 12-month freedom from CD-TLR (92.9%). The 12-month primary patency and freedom from CD-TLR in the ISR Imaging Freedom from core laboratory-assessed restenosis (duplex ultrasound PSVR ≤2.4) or clinically-driven target lesion revascularization through 12 months (adjudicated by a Clinical Events Committee). Number at risk represents the number of evaluable subjects at the beginning of the 30-day window prior to each follow-up interval. Brodmann M, et al JACC CI 2017

IN.PACT Global Study: ISR Imaging Cohort Freedom from Clinically-Driven TLR1 at 1 Year Clinically-driven TLR adjudicated by an independent Clinical Events Committee, blinded to the assigned treatment based on any re-intervention at the target lesion due to symptoms or drop of ABI of ≥20% or >0.15 when compared to post-procedure baseline ABI. Number at risk represents the number of evaluable subjects at the beginning of the 30-day window prior to each follow-up interval. Brodmann M, et al JACC CI 2017

IN.PACT Global Study: ISR Imaging Cohort Additional Outcomes IN.PACT™ Admiral™ DCB (N=131 Subjects) Clinically-Driven TLR1 7.3% (9/124) Any TLR 8.1% (10/124) Any TVR 9.7% (12/124) Primary Safety Endpoint2 91.1% (113/124) Major Adverse Events3 8.9% (11/124) All-Cause Death 0.0% (0/124) Major Target Limb Amputation Thrombosis 0.8% (1/124) Any re-intervention within the target lesion(s) due to symptoms or drop of ABI of ≥ 20% or > 0.15 when compared to post-index procedure baseline ABI. Composite of 30-day freedom from device- and procedure-related mortality and 12-month freedom from major target limb amputation and clinically-driven TVR. Major Adverse Events: Composite of death, major target limb amputation, clinically-driven TVR, and thrombosis. Brodmann M, et al JACC CI 2017

IN.PACT Global Study: ISR Imaging Cohort Summary Strong efficacy and safety in a complex lesion subset ISR lesions averaging 17.2 ± 10.5 cm 12-mo primary patency rate of 88.7% 12-mo CD-TLR rate of 7.3% Confirms the effectiveness of the IN.PACT™ Admiral™ DCB in the treatment of complex ISR lesions

DEBATE ISR- 1 year data

DEBATE ISR: 1 year outcome

DEBATE ISR- 36 months data showed catch up in the DEB group

Treatment of SFA ISR Zilver® PTX® Drug Eluting Stent Zeller et al. JACC Cardiovasc Intervent 2013

Zilver PTX - Freedom from TLR (1 year outcome)

Zilver PTX – Primary Patency (1 year outcome)

Acknowledgements 1) Sardar Farhan 2) Sandeep Singla 3) Ray Lascano 4) Vishal Kapur 5) Kartik Gujja 3) Dr. Krishnan