What s New in 2016? Prakash Krishnan MD FACC Director of Endovascular Services Cardiac Catheterization Laboratory Mount Sinai Medical Center New York

Transcription

1 What s New in 2016? Prakash Krishnan MD FACC Director of Endovascular Services Cardiac Catheterization Laboratory Mount Sinai Medical Center New York

2 Topics!! New Devices Data Algorithm based on data Question that need to be answered!

3 Where do we start! Fem-Pop segment- Patency in real world cohorts- Long lesion,cto Randomized data ISR Ca

4 Where do we start! BTK- We need to define endpoints as a whole Perform studies that are relevant to our patients We still have a long way to go!

5 Problems Lesion length CTO ISR Calcium

6 Answers Lesion length- DEB/DES Randomized Trials Zilver PTX InPact Levant II

7 Baseline Lesion Characteristics PTA Zilver PTX p-value Lesions Normal-to-normal lesion length (mm) 63 ± ± Stenosed lesion length (mm) 1,2 53 ± ± Diameter stenosis (%) 1 78 ± ± Total occlusions 27% 33% 0.20 De novo lesions 94% 95% 0.68 Lesion calcification 1 None 5% 2% 1 Angiographic core lab assessment 2 Region with > 20% diameter stenosis * Statistically significant Little 38% 26% Moderate 22% 35% Severe 35% 37% < 0.01*

8 5-year Primary Patency (PSVR < 2.0) Zilver PTX vs. Standard Care 66.4% Zilver PTX p < 0.01 log-rank 43.4% Optimal PTA + BMS At 5 years, Zilver PTX demonstrates a 41% reduction in restenosis compared to standard care

9 5-year Primary Patency (PSVR < 2.0) Provisional Zilver PTX vs. BMS 72.4% Provisional Zilver PTX p = 0.03 log-rank 53.0% Provisional BMS At 5 years, Zilver PTX demonstrates a 41% reduction in restenosis compared to BMS

10 5-year Freedom from TLR Zilver PTX vs. Standard Care 83.1% 67.6% Zilver PTX Optimal PTA + BMS p < 0.01 log-rank At 5 years, Zilver PTX demonstrates a 48% reduction in reintervention compared to standard care

11 Drug-Coated Balloon

12 SC A Current DCB Landscape 12-Month Patency 24-Month Patency 83.7% 89.9% 67.0% 73.5% 72.4% 55% 53.7% LEVANT I Lutonix TM* LEVANT 2 Lutonix TM* Italian Registry IN.PACTTM* IN.PACT SFA IN.PACT TM*. Scheinert, D., et al., J Am Coll Cardiol Inv, 2014;7: p Micari, A., et al., J Am Coll Cardiol Inv, 2012;5: p Tepe G. Presentation, Charing Cross London. US Dept of HHS FDA Executive Summary: Circulatory System Devices Advisory Panel June 12,2014: Bard Lutonix 035 Drug Coated Balloon PTA Catheter.

13 No Class Effect With DCBs Noticeable difference (15.8%) in patency rates and effect size between LEVANT 2 and IN.PACT SFA 12-Month Patency 89.8% LEVANT 2 IN.PACT SFA Num. of lesions Mean Length (mm) % 17.2% 56.8% 23% 66.8% Baseline stenosis 80.5% 81% Mean RVD Severe Calcification 10.4% 8.1% Occlusions 20.6% 25.8% De novo 83.9% 95% LEVANT 2 Lutonix 2 µg/mm2 TM* LEVANT 2 Unocated PTA Arm IN.PACT SFA IN.PACT 3 µg/mm2 TM* IN.PACT SFA Uncoated PTA Arm 1. US, Dept HHS. FDA Executive Summary: Circulatory System Devices Advisory Panel June 12,2014: Bard Lutonix 035 Drug Coated Balloon PTA Catheter. 2. Tepe G. Presentation. Charing Cross 2014, London, England. April SC A

14 1 IN.PACT SFA TRIAL EFFICACY OUTCOMES THROUGH 2 YEARS SUSTAINED PERFORMANCE BENEFIT OF IN.PACT ADMIRAL DCB OVER PTA THROUGH TWO YEARS 2 1. Freedom from core laboratory-assessed restenosis (duplex ultrasound PSVR 2.4) or clinically-driven target lesion revascularization through 24 months (adjudicated by a Clinical Events Committee blinded to the assigned treatment). 2. Number at risk represents the number of evaluable subjects at the beginning of the 30-day window prior to each follow-up interval. 14

15 1 IN.PACT SFA TRIAL EFFICACY OUTCOMES THROUGH 2 YEARS SUSTAINED PERFORMANCE BENEFIT OF IN.PACT ADMIRAL DCB OVER PTA THROUGH TWO YEARS 2 1. Freedom from core laboratory-assessed restenosis (duplex ultrasound PSVR 2.4) or clinically-driven target lesion revascularization through 24 months (adjudicated by a Clinical Events Committee blinded to the assigned treatment). 2. Number at risk represents the number of evaluable subjects at the beginning of the 30-day window prior to each follow-up interval.

16 IN.PACT SFA TRIAL ADDITIONAL EFFICACY OUTCOMES THROUGH 2 YEARS SUSTAINED PERFORMANCE BENEFIT OF IN.PACT ADMIRAL DCB OVER PTA THROUGH TWO YEARS 2-Year Outcome IN.PACT Admiral DCB (n = 220) PTA (n = 111) P-value 1 Clinically-driven TLR 2 9.1% (18/198) 28.3% (30/106) <0.001 All TLR % (20/198) 29.2% (31/106) <0.001 Primary Sustained Clinical Improvement % (133/173) 59.2% (61/103) ABI / TBI ± ± Unless otherwise indicated, all tests were for superiority using the Fisher s exact test for binary variables and t-test for continuous variables. 2.Clinically-driven TLR adjudicated by an independent Clinical Event 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. 3.All TLR includes clinically-driven and incidental or duplex driven TLR. 4.Freedom from target limb amputation, target vessel revascularization (TVR), and increase in Rutherford class. 5.TBI allowed in cases of incompressible vessels in IN.PACT SFA II phase. 16

17 What about real world lesions? No randomized data!! Zilver PTx Japanese post market study InPact/Lutonix Real world registry

18 Japan PMS Compared to RCT and SAS Zilver PTX RCT Zilver PTX SAS Zilver PTX Japan PMS No significant untreated inflow tract stenosis Key Sudy Criteria At least one patent runoof vessel Maximum 2 Zilver PTX stents Maximum 4 Zilver PTX stents per lesion per patient Lesion length < 14cm No exclusions One lesion per limb No Prior stent in SFA In-stent restenosis included All Patients treated with Zilver PTX enrolled (up to enrollment limit), NO exclusion criteria Excluded if serum creatinine > 2.0, renal failure, or dialysis No exclusions Antiplatelets Clopidogrel or ticlopidine recommended for 60 days, aspirin indefinitely Follow-up 5 Years 2 Years 5 Years Patency Core laboratory analysis Site analysis Stent Integrity X-ray core laboratory analysis Increasingly complex patients and lesions

19 Baseline Lesion Characteristics Zilver PTX RCT Zilver PTX SAS Zilver PTX Japan PMS Lesions Lesion length (cm) * 6.6 ± ± ± 9.7 Diameter stenosis (%) 80 ± ± ± 11 Total occlusions 30% 38% 42% In-stent restenosis (ISR) ** 0% 15% 19% Patent runoff vessels * Zilver PTX is indicated for lesions up to 140mm per leg and 280mm per patient ** Zilver PTX is not indicated for the treatment of in-stent restensosis 0 0% 0% 7% 1 22% 19% 32% 2 35% 35% 32% 3 42% 45% 29%

20 Freedom from TLR Months Freedom from TLR Zilver PTX RCT Zilver PTX SAS Zilver PTX Japan PMS 6 months 98.0% 97.6% 97.3% 1 year 91.6% 89.5% 91.4% 5 years 83.1% - TBD

21 Primary Patency by Duplex Ultrasonography Months Primary Patency by Duplex Ultrasonography Zilver PTX RCT (PSVR 2.0) Zilver PTX SAS (PSVR 2.0) Japan PMS (PSVR 2.4) 6 months 95.6% 96.3% 96.7% 1 year 90.2% 82.8% 84.8% 2 years 83.4% - TBD 5 years 72.4% - TBD

22 High stent integrity Fracture Rates Years Zilver PTX RCT (457 stents) Zilver PTX SAS (1889 stents) Japan PMS (1066 stents) 1 0.9% 1.5% 1.6% 3 1.9% - TBD 5 1.9% - TBD

23 Eluvia Drug-Eluting Vascular Stent System Design Goals Eluvia Drug-Eluting Vascular Stent System The Eluvia Drug-Eluting Vascular Stent System Design Goals: Ptx drug in a biostable polymer matrix loaded on to the Innova stent system Drug elution release of 85% at 1 year to match restenotic cascade Size matrix to accommodate various lesions Utilize a stent platform and triaxial delivery system BSC Data on File. Innova Vascular Stent System is an investigational device. Innova and Eluvia devices are not for sale in the U.S.

24 Drug Coated Balloon

25 Lesion Length: One of Many Challenges Unmet need in complex lesion types including long lesions, chronic total occlusions and in-stent restenosis No current treatment standard identified. Longer lesion length is a predictor of lower patency at 12 months post-procedure (35-65%) when associated with gold standard therapies of PTA and stenting subjects enrolled in the IN.PACT Global Study Long Lesion cohort intended to characterize performance of IN.PACT Admiral DCB in these types of long, complex lesions Clinical Cohort Total enrolment: 1,538 subjects, including >100 pts treated with 150 mm device Three Imaging Cohorts >450 subjects De NOVO ISR subcohort >150 subjects Long Lesion subcohort 157 subjects CTO sub-cohort >150 subjects 1. Lammer J et al. J Am Coll Cardiol 2013;62: Bosiers M et al. J Vasc Surg 2011;54:

26 IN.PACT Global Study Long Lesion Imaging Cohort: Baseline Clinical Characteristics N=157 Subjects Age (Y±SD) 69.5 ± 10.7 Male Gender (%) 66.2% (104/157) Diabetes (%) 41.0% (64/156) Insulin Dependent Diabetes Mellitus (%) 21.8% (34/156) Hypertension (%) 87.9% (138/157) Hyperlipidemia (%) 76.7% (115/150) Current Smoker (%) 34.4% (54/157) Obesity (BMI 30 kg/m²) (%) 22.1% (34/154) Coronary Heart Disease (%) 52.3% (80/153) Carotid Artery Disease (%) 22.4% (30/134) Renal Insufficiency 1 (%) 14.4% (21/146) Previous Peripheral Revasc. (%) 55.4% (87/157) Concomitant BTK Disease (%) 47.5% (67/141) ABI (mean ± SD) ± (147) Rutherford Clinical Category RCC4 10.3% RCC5 6.4% RCC3 61.5% RCC2 21.8% 1. Baseline serum creatinine 1.5 mg/dl Dierk Scheinert, MD, Drug coated balloon treatment for patients with intermittent claudication: new insights from the IN.PACT Global Study long lesion (>15cm) imaging cohort, europcr 2015

27 IN.PACT Global Study Long Lesion Imaging Cohort: Lesion and Procedural Characteristics Lesions (N) 164 Lesion Type: - de novo - restenotic (no ISR) - ISR Lesion Length (mean ±SD) 83.2% (134/161) 16.8% (27/161) 0.0% (0/161) ± 8.61 cm Total Occlusions 60.4% (99/164) Calcification Severe 71.8% (117/163) 19.6% (32/163) RVD (mm ±SD) ± Pre-treatment Diameter Stenosis (% ±SD) 90.9% ± 14.2 Device Success % (442/444) Procedure Success % (155/156) Clinical Success % (155/156) Pre-dilatation 89.8% (141/157) Post-dilatation 39.1% (61/156) Provisional Stent - LL cm: - LL > 25 cm: 40.4% (63/156) 33.3% (33/99) 52.6% (30/57) 1. Device success: successful delivery, inflation, deflation and retrieval of the intact study balloon device without burst below the RBP 2. 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) 3. Clinical success: procedural success without procedural complications (death, major target limb amputation, thrombosis of the target lesion, or TVR) prior to discharge Dissections: % (61/161) A-C 47.2% (76/161) D-F 14.9% (24/161) Dierk Scheinert, MD, Drug coated balloon treatment for patients with intermittent claudication: new insights from the IN.PACT Global Study long lesion (>15cm) imaging cohort, europcr 2015

28 IN.PACT Global Study Long Lesion Imaging Cohort: Kaplan-Meier Estimate of Primary Patency Number of subjects at risk* Baseline (day 0) 6 mo 12 mo IN.PACT Admiral DCB

29 IN.PACT Global Study Long Lesion Imaging Cohort: Primary Patency in Non-stented Subgroup Number of subjects at risk* Baseline (day 0) 6 mo 12 mo Non-Stented Pure LL Imaging Cohort

30 IN.PACT Global Study Long Lesion Imaging Cohort: Primary Patency by Lesion Length Subgroup Number of subjects at risk Baseline (day 0) 6 mo 12 mo Lesion Length cm Lesion Length >25 cm

31 IN.PACT Global Study Long Lesion Imaging Cohort: Safety & Effectiveness Outcomes by Lesion Length Subgroup LL cm (N=100) LL > 25 cm (N=57) Clinically-Driven TLR 1 2.3% (2/87) 12.8% (6/47) Primary Safety Endpoint % (85/87) 87.2% (41/47) Major Adverse Events 3 8.0% (7/87) 19.1% (9/47) Death (all-cause) 3.4% (3/87) 6.4% (3/47) Major Target Limb Amputation 0.0% (0/87) 0.0% (0/47) Thrombosis 2.3% (2/87) 6.4% (3/47) Any TLR 2.3% (2/87) 12.8% (6/47) Any TVR 2.3% (2/87) 12.8% (6/47) 1. 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 2. Composite of 30-day freedom from device- and procedure-related mortality and 12-month freedom from major target limb amputation and clinically-driven TVR 3. Major Adverse Events: Composite of death, major target limb amputation, clinically-driven TVR, and thrombosis Dierk Scheinert, MD, Drug coated balloon treatment for patients with intermittent claudication: new insights from the IN.PACT Global Study long lesion (>15cm) imaging cohort, europcr 2015

32 Results Across IN.PACT Clinical Studies Consistent clinical outcomes with the IN.PACT Admiral DCB across studies and complex femoropopliteal lesions. IN.PACT SFA Trial (DCB Arm) IN.PACT Global Study Long Lesion Cohort IN.PACT Global Study N=220 N=157 N=655 Lesion Length (cm) CD-TLR 2.4% 6.0% 8.7% CD-TVR 4.3% 6.0% 9.5% Thrombosis 1.4% 3.7% 3.8% Target Limb Major Amputation 0.0% 0.0% 0.3% Dierk Scheinert, MD, Drug coated balloon treatment for patients with intermittent claudication: new insights from the IN.PACT Global Study long lesion (>15cm) imaging cohort, europcr 2015

33 Problems Lesion length CTO ISR Calcium

34 Lesion Length: One of Many Challenges Unmet need in complex lesion types including long lesions, chronic total occlusions and in-stent restenosis No current treatment standard identified. Longer lesion length is a predictor of lower patency at 12 months post-procedure (35-65%) when associated with gold standard therapies of PTA and stenting subjects enrolled in the IN.PACT Global Study Long Lesion cohort intended to characterize performance of IN.PACT Admiral DCB in these types of long, complex lesions Clinical Cohort Total enrolment: 1,538 subjects, including >100 pts treated with 150 mm device Three Imaging Cohorts >450 subjects De NOVO ISR subcohort >150 subjects Long Lesion subcohort 157 subjects CTO sub-cohort >150 subjects 1. Lammer J et al. J Am Coll Cardiol 2013;62: Bosiers M et al. J Vasc Surg 2011;54:

35 Primary Patency at 1 Year ISR SUBGROUP ISR SUBGROUP 1 YEAR PRIMARY PATENCY CD-TLR AVERAGE LESION LENGTH 131 de novo ISR Lesions 88.7% 7.3% 17.2±10.5cm 35 UC IE 2015 Medtronic. All Rights Reserved. Medtronic, Medtronic logo and Further. Together are trademarks of Medtronic. Not for distribution in France, or Japan. 10/15

36 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 250 lesions crossable by guidewire 169 ELA + PTA Primary Safety endpoint at 37 days (n=155) 81 PTA 7 lesions uncrossable Primary Safety endpoint at 37 days (n=73) Primary Efficacy endpoint at 212 days (n=117) Primary Efficacy endpoint at 212 days (n=56)

37 Excimer Laser Atherectomy Catheters Turbo Elite Pilot channel creation Turbo Tandem Biased laser catheter for large lumen ablation

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

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

40 Data is upcoming!!! DEB/DES-CTO

41 Problems Lesion length CTO ISR Calcium

42 DCB and Calcium IN.PACT DCB and Calcium Prospective Study (n=60) 12 month Results 100% 100% 100% 100% 90% 90% % % % % 50% % Primary Patency LLL % 0.0 1a 1b 2a 2b 3a 3b 4a 4b Calcium distribution and severity affect LLL and primary patency Ca ++ represents a barrier to optimal drug absorption Calcium distribution evaluation by CTA (circumf.) and DSA (longitud.) F. Fanelli Cardiovasc Interv Radiol 2014

43 Levant 2 Trial Angiographic Characteristics (ITT) D. Scheinert LINC 2015

44 Levant 2 Trial Sub-analysis Calcified Lesions Kaplan Meier analysis, 38 events 67 at risk D. Scheinert LINC 2015

45 Correct choice of stent design can minimize struts stress while maintaining a patent lumen High circumferential stress values at the internal elastic lamina are most likely to disrupt this structure, provoking neintimal growth leading to restenosis

46 SUPERA stent Interwoven self-expanding nitinol stent Six pairs of super-elastic nitinol wires which are interwoven in a helical pattern in a closed cell geometry 1) Radial strength 2) Flexibility and Durability 3) Conformability 4) Kink, Crush and Fracture resistant Supports the natural movement of the vessel

47 SUPERB Results Primary Patency (VIVA) Primary Patency (K-M) Freedom from TLR (K-M) 79.0% 86.3% 89% 84% 83% 12 Months 24 Months 36 Months Patient Baseline 264 Ave. Lesion Length (cm) 7.8 Fracture Rate (%) 0* % Distal SFA/PPA 34 Occlusions (%) 25 Severe Calcium (%) 45 Rutherford 1-3 (%) 95 Rutherford 4 (%) 5 PSVR 2.0

48 SUPERB Results in Long Lesions Consistent results across lesion lengths Non-Restenosis Rate by Lesion Length (12 months SUPERB IDE TRIAL) PSVR 2.0

49 Freedom from TLR (K-M) by Percent Compression / Elongation at 12, 24, and 36 months Optimal Deployment Leads to Low Re-intervention Rate Out to 3 Years SUPERB freedom from TLR at 1, 2, and 3 years 100% 90% 80% 90% 90% 90% 91% 87% 87% 97% 96% 94% 84% 78% 87% 82% 78% 78% 77% 12 months 24 months 36 months 70% 60% 63% 50% 40% 42% 30% 20% 10% 0% Moderate (21-40%) Minimal (11-20%) Nominal (± 10%) Minimal (11-20%) Moderate (21-40%) Severe (>40%) n=6 n=22 n=74 n=38 n=39 n=26 Compressed Nominal Elongated

50 Comparative Data Between DCB and DES Therapies 89.8% Primary Patency (KM Day 360) 73.5% 82.7% CD-TLR (12 month) 12.3% 9.6% 2.4% IN.PACT SFA LEVANT II Zilver PTX IN.PACT SFA LEVANT II* Zilver PTX Note: Primary patency and TLR rates are not directly comparable; chart is for illustration only. IN.PACT SFA/LEVANT II represent DCB arms of trial; ZILVER PTX represents DES arm of trial. * Data from LEVANT II represents total TLR.

51 Comparative Data Between DCB and DES Therapies 12-month Binary Restenosis 36.0% 16.5% 23.5% IN.PACT SFA (DCB) LEVANT II (DCB) Zilver PTX PSVR >2.4 PSVR 2.5 PSVR >2.0 Source: FDA SSED Table 16 Source: FDA Exec Summary Table 37 Source: FDA SSED Table 25 Note: Binary restenosis rates are not directly comparable; chart is for illustration only; IN.PACT SFA and LEVANT II binary restenosis rates determined by same independent core laboratory.

52 New in 2016! Algorithm based on DATA

53 SFA Treatment Strategy - Proposal Stenosis PTA predilatation Flow-limiting dissection or >50% residual stenosis? Yes DES/Supera No Is the lesion severely calcified? No DCB Flow-limiting dissection or >50% residual stenosis? No Finished Yes Post-Dilatation Stent (spot supera)

54 SFA Treatment Strategy - Proposal Stenosis PTA predilatation Flow-limiting dissection or >50% residual stenosis? Yes DES/Supera No Is the lesion severely calcified? No Yes Consider atherectomy Debulk successful? DCB Yes No Flow-limiting dissection or >50% residual stenosis? Supera No Finished Yes Post-Dilatation Spot Supera)

55 SFA Treatment Strategy - Proposal Stenosis CTO PTA predilatation Required (US); Optional (Europe) Yes Can it be crossed? Flow-limiting dissection or >50% residual stenosis? Yes Stent No No Bypass Is the lesion severely calcified? No Yes Consider atherectomy Debulk successful? DCB Yes No Flow-limiting dissection or >50% residual stenosis? Stent No Finished Yes Post-Dilatation Stent (spot stent)

56 Thank You

57 What s New in 2016? Prakash Krishnan MD FACC Director of Endovascular Services Cardiac Catheterization Laboratory Mount Sinai Medical Center New York