Drug Eluting Stents: The only SFA Advance with 5-year Outcomes Gary M. Ansel, MD System Medical Chief: Vascular OHioHealth/Riverside Methodist Hospital Columbus, Ohio Self-expanding Stents Pro Simple Safe Quick Randomized superiority data to PTA Stent fractures Con Cost Restenosis difficult to treat Inferior to DES in randomized trial data Stents Improve Ambulation: BLASTER 9 month Treadmill Results Measured in Time/minutes Parameter Baseline 9 Month Change SMART with Abciximab 2.65 1.91 (0.47 7.50) 3.95 2.84 (1.00 10.00) 0.96 2.05 (-3.00 3.72) SMART without Abciximab 2.65 2.07 (0.50 7.03) 4.43 2.49 (0.50 10.00) 1.78 2.85 (-4.62 8.58) All Patients 2.65 1.97 (0.47 7.50) 4.17 2.67 (0.50 10.00) 1.35 2.47 (-4.62 8.58) Ansel et al;cath cardiovasc Interven 2006 1
Randomized Stent Results: (Resilient: 12 and 36-Month(TLR) Results) 100% 80% 60% 40% 86% p=.91 86% 38% 80% 46% 87% PTA PTA+LifeStent 3-yr 75.5% vs. 41.8%, 34% 72% 20% p<.0001 p<.0001 p<.0001 0% Freedom from MACE* Prim. Patency (duplex)* Freedom from TLR* Clinical success Laird et al Circ Cardiovasc Interv. 2010 Jun 1;3(3):267-76 Laird et al. J Endovasc Ther. 2012 Feb;19(1):1-9 Intimal vs subintimal stenting? Retrospective analysis of > 900 pts intraluminal subintimal Patency primary 3 year 55% 53% Patency secondary 3 year 80% 85% Soga et. al. J Vasc Surg 2013:58;1547-55 Stent Grafts: Randomized Comparison to Surgical Prosthetic Bypass N = 86 pts (100 limbs) Stent graft 50 Surgical bypass 50 Mean stent graft treatment length = 25.6 cm SG Bypass 1-year patency Primary 73.5% 74.2% Secondary 83.9% 83.7% 2-year patency Primary 62% 65% Secondary 73% 75% Kedora et al J Vasc Surg 2007;45:10-16 McQuade et al. J Vasc Surg. 2009 Jan;49(1):109-15 2
Error bars = 95% confidence interval VIBRANT 1-YR Interim Results: Lesion Characteristics: Diffuse and complex LESION CHARACTERISTICS GORE VIABAHN Endoprosthesis Bare Nitinol Stent p-value TREATED OCCLUSIONS 59.7% 56.6% 0.74 TARGET LESION LENGTH (cm) 0.87 Mean (Std Dev) 19 (8) 18 (7) Median (Range) 20 (8 40) 16 (8 36) LESION CALCIFICATION 0.01 None Mild 37.5% 57.9% Moderate Severe 62.5% 42.1% TIBIAL RUNOFF 0.10 1 Vessel 15.3% 22.4% 2 Vessel 50.0% 32.9% 3 Vessel 34.7% 44.7% Geraghty et al. J Vasc Surg. 2013 May 13 VIBRANT (SG vs PMS) 3 year Data 100% * Percentage of Patients (%) 80% 60% 40% 20% * 0% Primary Primary Secondary Freedom Primary Primary Secondary Freedom Patency Assisted Patency from TLR Patency Assisted Patency from TLR Patency Patency GORE VIABAHN Endoprosthesis Bare Nitinol Stent End of 12 month F/U Window * p < 0.05 End of 36 month F/U Window Comment on cross-over: Sixteen Bare Nitinol Stent patients received the VIABAHN Endoprosthesis during subsequent reinterventions, which complicates secondary endpoint comparisons. Geraghty et al. J Vasc Surg. 2013 May 13 Future Stent Designs 3
SUPERB TRIAL Freedom from Loss of Primary Patency at 1 Year (PSVR < 2.0) 98.4% 6 month patency N = 264 Mean lesion 8cm 86.1% primary patency Freedom from TLR = 90% TCT 2012 Survival Analysis conducted by HCRI VIPER Registry (Heparin/Contoured): One-Year Patency 92% 87% 74% 12 month duplex follow-up available for 103 / 120 patients Saxon et al. J Vasc Interv Radiol. 2013 Feb;24(2):165-73 VIASTAR:Primary Patency VIPER: Effects of Device Sizing: Proximal Per Protocol Analysis, End-of-window patency 78% 78% 91% 73% p < 0.01 54% 53.5% 70% p = 0.004 33% VIABAHN, n = 66 BMS, n = 63 VIABAHN, n = 37 BMS, n = 23 p < 0.05 All Lesions n= 38 n= 57 Lesions 20 cm Now need longer term data Device oversizing assessed by independent Core Lab, data on file 4
Drug Coated Balloons Fempop: DCB vs PTA Levant 2 Fempop:InPactTrial DCB vs PTA Inpact 1 year 5
Fempop: DCB vs PTA InPact Trial: 1 year Polymer Based DES Results SIROCCO STRIDES 68.5% Zilver PTX Study Design Primary Randomization Enrollment PTA Zilver PTX Provisional BMS Suboptimal PTA Optimal PTA Secondary Randomization Provisional Zilver PTX 6
Baseline Lesion Characteristics PTA Zilver PTX p-value Lesions 251 247 Normal-to-normal lesion length (mm) 63 ± 41 66 ± 39 0.36 Stenosed lesion length (mm) 1,2 53 ± 40 55 ± 41 0.71 Diameter stenosis (%) 1 78 ± 17 80 ± 17 0.38 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* 5-year Stent Integrity Study Period Number of New Events Fracture Rate 1 Enrollment 0 0.0% 1-year 4 0.9% 3-year 3 1.9% 5-year 0 1.9% 1 Kaplan-Meier estimates Zilver PTX has excellent durability in challenging SFA environment 3-Year Freedom from TLR Zilver PTX vs. Standard Care 83.7% 70.2% Zilver PTX 240 patients Optimal PTA + Bare Zilver 139 patients p < 0.01 log-rank 3-year TLR Group Rate Reduction Zilver PTX 16.3% Optimal PTA + 29.8% 45% Provisional Bare Zilver 7
5-year Freedom from TLR Zilver PTX vs. Standard Care 83.1% Zilver PTX p < 0.01 log-rank 67.6% Optimal PTA + BMS Years (PATIENTS) 0 1 2 3 4 5 At Risk 305 260 220 187 164 133 Zilver PTX Failed 0 25 40 46 47 47 At Risk 172 125 106 88 78 69 Standard Care Failed 0 33 44 48 51 51 At 5 years, Zilver PTX demonstrates a 48% reduction in reintervention compared to standard care 5-year Primary Patency (PSVR < 2.0) Zilver PTX vs. Standard Care 66.4% Zilver PTX 43.4% Optimal PTA + BMS p < 0.01 log-rank Years (LESIONS) 0 1 2 3 4 5 Zilver PTX Standard Care At Risk 318 246 199 163 137 109 Failed 1 48 71 83 92 94 At Risk 183 108 64 52 44 38 Failed 0 57 73 79 84 86 At 5 years, Zilver PTX demonstrates a 41% reduction in restenosis compared to standard care 5-year Primary Patency (PSVR < 2.0) Zilver PTX vs. Standard Care 66.4% Zilver PTX 43.4% Optimal PTA + BMS From 1-5 years, the relative separation increases by 35% 8
5-year Clinical Benefit Index Zilver PTX vs. Standard Care 79.8% Zilver PTX p < 0.01 log-rank 59.3% Optimal PTA + BMS Years (PATIENTS) 0 1 2 3 4 5 At Risk 301 247 206 179 158 129 Zilver PTX Failed 0 38 52 56 57 57 At Risk 170 109 94 76 67 60 Standard Care Failed 0 48 56 61 64 64 At 5 years, Zilver PTX has a superior rate of freedom from persistent or worsening claudication, rest pain, ulcer, or tissue loss 5-year Freedom from TLR Provisional Zilver PTX vs. BMS Provisional 84.9% Zilver PTX p = 0.06 log-rank 71.6% Provisional BMS Years (PATIENTS) 0 1 2 3 4 5 Provisional Zilver PTX Provisional BMS At Risk 60 53 47 39 34 31 Failed 0 3 6 7 8 8 At Risk 54 41 36 29 27 23 Failed 0 9 12 13 14 14 At 5 years, Zilver PTX demonstrates a 47% reduction in reintervention compared to BMS 5-year Primary Patency (PSVR < 2.0) Provisional Zilver PTX vs. BMS Provisional 72.4% Zilver PTX p = 0.03 log-rank 53.0% Provisional BMS Years (LESIONS) 0 1 2 3 4 5 Provisional Zilver PTX Provisional BMS At Risk 63 55 46 38 31 25 Failed 0 6 10 11 14 15 At Risk 62 42 35 29 26 19 Failed 0 15 20 23 24 26 At 5 years, Zilver PTX demonstrates a 41% reduction in restenosis compared to BMS 9
5-year Clinical Benefit Index Provisional xzilver PTX vs. BMS 81.8% Provisional Zilver PTX p = 0.02 log-rank 63.8% Provisional BMS Years (PATIENTS) 0 1 2 3 4 5 Provisional Zilver PTX Provisional BMS At Risk 64 54 48 42 38 34 Failed 0 8 10 10 11 11 At Risk 54 36 32 25 23 20 Failed 0 14 16 17 18 18 At 5 years, Zilver PTX has a superior rate of freedom from persistent or worsening claudication, rest pain, ulcer, or tissue loss Can Results be Generalized OUS Registry: Subgroups Freedom from TLR Subgroup 12 Months 24 Months Overall 89% (n = 818) 82% (n = 427) De novo (all) 91% 88% < 7 cm Lesions 94% 91% > 7 cm to 15 cm Lesions 92% 86% > 15 cm Lesions 84% 80% TASC C and D* 87% 78% Occlusions 86% 77% Stenosis 90% 85% Restenosis (all) 81% 70% Restenosis (not ISR) 87% 73% In-stent Restenosis (ISR) 78% 69% *TASC 2000 Conxclusions for 5-year Zilver PTX RCT As the first randomized controlled SFA device trial with 5-year follow-up, these results with the Zilver PTX stent provide important insights regarding long-term outcomes for endovascular treatment 5-year data for Zilver PTX versus standard care Greater than 40% reduction in reintervention and restenosis Superior clinical benefit These benefits increase with time results with Zilver PTX continue to diverge from standard care over 5 years with no late catch-up 5-year results confirm long-term superiority of Zilver PTX versus bare metal stents 10
1/19/2015 DCB: Should You Add Them to Your Arsenal? Mahmood Razavi, MD, FSIR, FSVM Director Center for Clinical Trials Heart & Vascular Center Vasc & Interv Specialists of Orange Disclosures (2014/15) Advisor/consultant 480 Biomedical Abbott Vascular Bard Peripheral Vasc Boston Scientific Cagent Vasc Codman/ J&J Covidien Microvention/Terumo Reflow Trivascular Veniti Yawa Med Training/speaking/hon. Penumbra Covidien Gore Stocks 480 Biomedical Embo Medical Embomedics Neuravi Reflow Medical Trivascular Yawa Med Current Endo-Technologies Are Suboptimal Limitations of traditional endovascular technologies (POBA, BMS, & simple debulking) are well known & mechanisms of failure are better understood Need to move beyond simple mechanical approaches Do DCBs offer any advantage? How should they optimally be used? 1
1/19/2015 Current Solutions: Drug-Device Combinations Drug-eluting stents (DES) Drug-coated balloons (DCB) Adjunctive adventitial drug delivery Bioabsorbable drug eluting scaffolds (BVS) Debulking + drug delivery Drug-Coated Balloons Do DCBs offer any advantage over the traditional approaches? How should they optimally be used? DCB: Advantages Short learning curve Issues: Pre-dilation & geographic miss No implants No stent fx issues No stimulus for chronic inflammation (COF) Potentially more options for re-treatment?? May reduce need for long term antiplatelet tx May be a better option for no stent zones 2
1/19/2015 Lutonix Peripheral DCB (Lutonix/ C.R. Bard Inc) Drug: Paclitaxel 2 μg/mm 2 1 μ thick uniform non-flaking coating Balloon inflation transfers the drug to the endoluminal surface of the vessel PTX diffuses into the vessel wall Drug LEVANT-2 Trial Global prospective, multicenter, single blind, randomized study of Lutonix DCB vs PTA (2:1 randomization) Duplex & angiographic core labs with CEC & independent DSMB 543 subjects enrolled at 54 US & EU sites LEVANT-2 Trial Design Primary Efficacy Endpoint: Primary patency through 12 months defined as absence of binary restenosis (PSVR 2.5) and CD-TLR Primary Safety Endpoint: Composite of 30-day all cause POD and 1- yr freedom from index limb amputation, re-intervention, and limb-related death 3
1/19/2015 Efficacy Endpoint of Primary Patency Levant-2 Achieved Primary Patency CO 80 = 12.6% p=0.015 Percent (%) 70 60 50 40 30 20 10 0 n=172 65.2 Lutonix DCB N=264 n=71 52.6 Standard PTA N=135 CO-6 Primary Primary Patency Patency (Kaplan-Meier) % Free from Primary Patency Event 100 90 80 70 60 50 40 30 20 10 Lutonix DCB (N) 291 Standard PTA (N) 146 0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 Months from Randomization Date 261 116 DCB PTA 179 69 p<0.001 Primary Efficacy Endpoint Through 24-Months Primary Efficacy (Preliminary Through Data) 24-Months CO-18 % Free from Primary Patency Event 100-90 - 80-70 - 60-50 - 40-30 - 20-10 - 0 - Lutonix DCB (N) 291 Standard PTA (N) 146 Survival % Time Lutonix DCB Standard PTA p-value 730 days 53.7% 48.4% 0.0205 179 69 DCB PTA p=0.0205 0 6 12 18 24 Months from Randomization Date 26 14 4
1/19/2015 CO-23 Primary Safety Primary Events Safety Events Safety Event (Patients may have > 1 event) Lutonix DCB %(n/n) Standard PTA %(n/n) Perioperative ( 30) death 0.0% (0/308) 0.0% (0/155) Index Limb Related death at 12 months 0.0% (0/285) 0.0% (0/140) Amputation at 12 months 0.3% (1/286) 0.0% (0/140) AV fistula surgery at 12 months 0.4% (1/285) 0.0% (0/140) Surgical bypass at 12 months 0.7% (2/285) 0.7% (1/140) Total TLR at 12 months 12.3% (35/285) 16.8% (24/143) Non-TLR TVR at 12 months 1.1% (3/285) 1.4% (2/143) Index limb interventions in non-target vessels at 12 months 2.1% (6/285) 2.9% (4/140) IN.PACT DCB Balloon (Medtronic Inc.) Drug: Paclitaxel Excipient: Urea Urea hydrates upon contact with blood & drug released Paclitaxel binds to the vessel wall Paclitaxel penetrates into media & adventitia Can remain there for over 180 days at therapeutic levels IN.PACT SFA Trial Prospective, multicenter (EU & US), single blinded, randomized study of IN.PACT DCB vs PTA (2:1) Blinded Duplex & angiographic core labs with CEC Independent DSMB Primary endpoints at 12 months with 5-yr follow up 5
1/19/2015 Trial Design Screen Failure (treat per std practice) Trial design RC 2-3-4 [1] Clinical and Anatomic Inclusion / Exclusion Criteria SUCCESSFUL PRE-DILATATION [2] Pre-screening Screening NO 331 Randomization Randomized 2:1 IN.PACT (220) PTA (111) Provisional Stenting? NO Secondary Analysis (331 ITT ALL Subjects) Primary Analysis (301 ITT NON-Stented Subjects) Laird J. TCT 2014 1. With symptoms of claudication and/or rest pain and angiographic evidence of SFA/PPA stenosis Trial Design Primary Efficacy Endpoint: Primary patency through 12-months, defined as freedom from clinically-driven TLR and Duplex restenosis (PSVR 2.4) Primary Safety Endpoint: Procedure related death @ 30-d and freedom from clinically driven TVR & major amputation of index limb through 12-months Baseline Clinical Characteristics Charecteristics IN.PACT DCB PTA p N 220 111 Age (Y) 67.5 ± 9.5 68.0 ± 9.2 0.612 Male Gender (%) 65.0% (143/220) 67.6% (75/111) 0.713 Diabetes (%) 40.5% (89/220) 48.6% (54/111) 0.161 Hypertension (%) 91.4% (201/220) 88.3% (98/111) 0.431 Hyperlipidemia (%) 84.5% (186/220) 82.0% (91/111) 0.637 Current Smoker (%) 38.6% (85/220) 36.0% (40/111) 0.719 Coronary Artery Disease (%) 57.0% (122/214) 55.0% (60/109) 0.813 Carotid Artery Disease (%) 34.9% (73/209) 31.7% (32/101) 0.610 Laird J. TCT 2014 Rutherford Stage (%) 2 3 4 5 ABI / TBI [1] 0.769 ± 0.228 0.744 ± 0.189 0.308 37.7% (83/220) 57.3% (126/220) 5.0% (11/220) 0.0% (0/220) All ITT subjects (stented and non-stented) 37.8% (42/111) 55.9% (62/111) 5.4% (6/111) 0.9% (1/111) 0.898 6
1/19/2015 Baseline Angiographic Characteristics Lesion Type [1] De novo Restenotic IN.PACT DCB PTA p (N=220 Subjects, N=221 Lesions) 95.0% (209/220) 5.0% (11/220) All ITT subjects (stented and non-stented) (N=111 Subjects, N=113 Lesions) 94.6% (105/111) 5.4% (6/111) # Patent Runoff Vessels 0 3.3% (7/212) 4.5% (5/112) 1 13.7% (29/212) 26.8% (30/112) 2 41.5% (88/212) 33.0% (37/112) 3 41.5% (88/212) 35.7% (40/112) 0.875 0.042 Prox. Popliteal Involvement (%) 6.8% (15/221) 7.1% (8/113) 1.000 Lesion Length (cm) [2] 8.94 ± 4.89 8.81 ± 5.12 0.815 Total Occlusions (%) 25.8% (57/221) 19.5% (22/113) 0.222 Severe Calcification (%) 8.1% (18/221) 6.2% (7/113) 0.662 RVD (mm) 4.647 ± 0.841 4.681 ± 0.828 0.728 MLD pre (mm) 0.900 ± 0.776 0.933 ± 0.771 0.711 Diameter Stenosis pre (%) 81.1 ± 15.5 81.3 ± 13.7 0.946 Laird J. TCT 2014 12 Months Results: IN.PACT SFA Randomized Controlled Trial Per Protocol, 12-month Outcomes 1. Primary patency is defined as freedom from clinically-driven TLR and freedom from restenosis as determined by duplex ultrasound (DUS) Peak Systolic Velocity Ratio (PSVR) 2.4 2. Primary patency comparative statistics imputed missing data and non-stented ITT were adjusted for Propensity Score 3. Primary safety composite is defined as freedom from device and procedure-related 30-day death and freedom from target limb major amputation and clinically-driven TVR through 12 months 4. Non-inferiority margi 10% 5. Non-stented ITT cohort difference adjusted for (3) Propensity freedom Score 6. from p-value TVR, associated TLR with & sequential increase superiority in RB test class @ 1 yr Laird J. TCT 2014 ALL ITT, 12-month Effectiveness Outcomes IN.PACT DCB PTA p PrimaryPate cy(psvr 2.4) 82.2% (157/191) 52.4% (54/103) <0.001 Clinically-driven TLR [1] 2.4% (5/207) 20.6% (22/107) <0.001 All TLR [2] 2.9% (6/207) 20.6% (22/107) <0.001 Primary Sustained Clinical Improv. [3] 85.2% (167/196) 68.9% (73/106) <0.001 ABI / TBI [4] 0.951 ± 0.221 0.886 ± 0.169 0.002 ALL ITT, 12-month 12-Month Primary Patency Patency [1] (All Patients ITT Analysis) (p<0.001 by log-rank test) Laird J. TCT 2014 7
1/19/2015 ALL ITT, 12-month Clinically-driven TLR 12-Month Clinically Driven TLR (All Patients ITT Analysis) IN.PACT PTA p Clinically-driven TLR [1] 2.4% 20.6% <0.001 [2] (p<0.001 by log-rank test) Laird J. TCT 2014 1. Clinically-driven TLR defined as any re-intervention due to symptoms or drop of ABI/TBI of >20% or >0.15 compared to post-procedure ABI/TBI IN.PACT SFA IN.PACT Global and SFA and Registry IN.PACT Global IN.PACT (n=1483) Global 12-months Results Summary ~ 12-months 45% of data analyzed Results & adjudicated Summary by CEC IN.PACT SFA IN.PACT CD-TLR (DCB IN.PACT Arm) SFA N=220 (DCB Arm) N=220 2.4% Global IN.PACT N=655 Global N=655 8.7% CD-TLR CD-TVR 2.4% 4.3% 8.7% 9.5% CD-TVR Thrombosis 4.3% 1.4% 9.5% 3.8% Thrombosis Target Limb Major Amputation 1.4% 0.0% (0) 3.8% 0.3% (2) Target Limb Major Amputation 0.0% (0) 0.3% (2) Ansel G. TCT 2014 IN.PACT SFA IN.PACT Global IN.PACT SFA IN.PACT Global Lesion Length 8.9 cm 12.2 cm Lesion CTO Length 25.8% 8.9 cm 35.8% 12.2 cm ISR CTO 0.0% 25.8% 21.4% 35.8% Baseline RC ISR > 3 5% 0.0% 15% 21.4% Baseline RC > 3 5% 15% What about ISR? 8
1/19/2015 DCB in ISR Author/yr Therapy Number Lesion length (mm) 1-yr 1 patency 1-yr TLR Stabile/ 12 DCB 39 83 ± 39 92% 8% Gandini/ 13 Laser + DCB 24 200 ± 101 67% 17% Gandini/ 13 DCB 24 233 ± 91 38% 50% Sixt/ 13 Excisional + DCB VanDenBerg 13 29 153 ± 93 85% NR Laser+ DCB 108 133 ± 92 79% 19% Liistro 14 DCB 44 132 ± 86 80% 14% Patency appears better than PTA alone Applications of DCB De novo fempop lesions in sx pts In combination with debulking Outcome v. DES or BMS not well established ISR Failed/failing dialysis access BTK lesions (?) One failed trial, 2 nd enrolling, 3 rd will begin enrollment in 2016 Conclusion Answer: definitive YES! 9
1/20/2015 VuMedi Webinar - Current Advances in SFA Interventions Cases and Applications of Bare Metal Stents and Vascular Mimetic Implants: Growing Data & Equal Results January 20, 2015 Sahil A. Parikh, M.D. Assistant Professor of Medicine Director, Center for Research and Innovation Director, Experimental Interventional Cardiology Laboratory Director, Interventional Cardiology Fellowship Program Harrington Heart & Vascular Institute University Hospitals Case Medical Center Case Western Reserve University School of Medicine Cleveland, Ohio Disclosures Consulting/Speakers Bureau: Medtronic, Boston Scientific, Abbott Vascular, St. Jude Medical, Astra Zeneca, Edwards, Cordis, Janssen, CR Bard, Abiomed Research: Medtronic, Boston Scientific, IDEV Technologies/Abbott Vascular, Daiichi Sankyo, Lutonix/CR Bard, TriReme Medical I will be discussing off label applications of approved medical devices The Typical Claudicant 45 yo male with DM2, Dyslipidemia, HTN and Rutherford 2-3 symptoms for 3 months Works as a janitor in a large downtown office building unable to perform work Diminished pulses noted on physical examination in his podiatrist s office ABI: 0.6R and 0.8L Referred for evaluation 1
1/20/2015 Examination 150/70, 66, 16, 98% JVP 6, Carotids 2+, soft L bruit CTA &P RRR S4 S1 S2 and no murmur No abd bruit Fem: 2+, 2+ Pop: Tr, 1+ DP: Monophasic, Biphasic PT: Monophasic, Biphasic What next? Risk factors treated to target Supervised Exercise Therapy recommended Patient continues to be vocationally limited No improvement with Cilostazol ACC/AHA Guidelines for the Management of Patients with Peripheral Arterial Disease Hirsch AT, et al. J Am Coll Cardiol. 2006;47:e1-e192. 2
1/20/2015 Aortography Runoff Angiography Bilateral SFA disease with focal L SFA stenosis and CTO R SFA (~15cm) BTK: 2V runoff bilaterally Up and Over SFA Selective DSA of the R SFA 3
1/20/2015 Questions Treatment Options: 1. Fem-Pop bypass with autogenous vein 2. Fem-Pop bypass with eptfe 3. SFA CTO endovascular revascularization antegrade 4. SFA CTO endovascular revascularization retrograde 5. Stem Cell Therapy TASC II Lesion Descriptions and Recommended Therapy of Femoral Artery Stenosis/Occlusion Norgren L et al. JVS. 2007:S5A S67A Femoropopliteal Disease: Open vs Endovascular Approaches OPEN SURGICAL 40%-75% 5 year patency rate depending on conduit Limb salvage rates are 70% at 5 years 1%-3% mortality rate Torsion Extension / Contraction ENDOVASCULAR Excellent procedural success Reported patency varies widely 30% 85% at 1 year Very little comparative Flexion effectiveness data exist comparing different therapies including stents, drug coated balloons and drug eluting stents Compression 4
1/20/2015 ABOVE-knee femoral popliteal bypass 5-year patency Table PTA/stents 3. The 5-year patency of Femoral-popliteal 55-75% different types of conduits Surgical reconstruction Femoral-popliteal 65-80% Vein Femoral-tibial 74 76% 60-75% eptfe Graft 39 52% AbuRahma et al, 1999; Green et al, 2000; Johnson and Lee, 2000; Klinkert et al, 2003 SFA Stenting is Superior to PTA Alone 32% Crossover due to inadequate PTA result Schillinger et al., NEJM 2006 After Endovascular Intervention, SFA Patency Decreases with Lesion Length for PTA and Conventional Stenting Conventional PTA Nitinol Stents Slope of relationship between length and restenosis is steeper for PTA compared to stenting Gray B. CCI. 2011 5
1/20/2015 A Risk Stratification Score Predicts Patency in TASC C/D Lesions Risk Factor Points Female 1 Diabetes 1 Dialysis 1 CLI 1 Lesion >150mm 2 Poor Runoff 1 Risk Score Category 0-2 Low 3-4 Moderate 5-7 High Soga, et al. JVS 2011 Question: CTO Crossing Technique Options: 1. Wire and Catheter Intraluminal (Antegrade or Retrograde) 2. Wire and Catheter Subintimal (Antegrade or Retrograde) 3. CTO Crossing Device CTO Crossing 6
Angio image courtesy of Dr. Hans Biemans, Rivas Hospital Gorinchem, the Netherlands. 1. Scheinert, et al., Real world perspectives of treating complex SFA-Pop lesions, Results from the SUPERA-500 Registry, LINC 2013. 2. Characteristically round lumens supported by Arena, F.J., Arena, F.A. Intravascular Ultrasound Evaluation of Interwoven Nitinol Stents at Implant. J Vasc Med Surg. 2013:1;116. Data on file at Abbott Vascular. 1/20/2015 Question: SFA Treatment Choices PTA alone Nitinol Stent Conventional Nitinol Stent Vascular Mimetic Implant Drug Eluting Stent Drug Coated Balloon Stent Graft Atherectomy Alone Orbital vs Directional vs Aspiration vs Laser Atherectomy + Stent Drug Coated Balloon + Stent The Supera Vascular Mimetic Implant (VMI) Provides Flexibility, Radial Strength and Kink Resistance The Supera implant mimics the natural structure and movement of the anatomy An interwoven nitinol design creates an implant that supports rather than resists the vessel Resists kinking and fracture with minimal chronic outward force Maintains a round, open lumen for normal, healthy blood flow in challenging anatomy 2 7
Source: Supera Peripheral Stent System Instructions for Use. 1. PSVR < 2.0. 2. Garcia, L., SUPERB Pivotal IDE Trial, 12-Month Results, TCT 2012 for Ankle-Brachial Index improvements. 3. One patient (1/200, 0.5%) experienced a Type III fracture at 24 months. The patient had a revascularization with directional atherectomy for in-stent restenosis at 9 months post index procedure. At 12-month follow up there was no evidence of a stent fracture. Additional in-stent restenoses were treated twice more with directional atherectomy between the 12- and 24-month evaluations. At 24 months, a type III fracture was noted in x- ray in the region of the earlier restenoses. There was no report of a major adverse event at 24 months. 1/20/2015 Vascular Mimetic Implants have Superior Kink Resistance Compared to Nitinol Stents Standard Nitinol Stents Supera implant AP View Lateral View Courtesy Abbott Vascular. SUPERB Trial SFA and proximal popliteal trial including complex patients Study Overview: 264 subjects (ITT), 34 sites Prospective, multi-center, un-blinded, single-arm versus PTA performance goal Stenotic, restenotic (non-stented) or occluded lesions Core laboratory used Primary safety endpoint: 99.2% free from composite death, TLR and amputation at 37 days Primary effectiveness endpoint (VIVA): 78.9% primary patency at 12 months 3 Patency (K-M): 86.3% primary patency at 12 months 3 72.7% severe/moderate calcification 1 78 mm mean lesion length 2 86% mid/distal SFA 1 Source: Supera Peripheral Stent System Instructions for Use. Data on file at Abbott Vascular. 1. Percent of lesions. 2. 20-20, Core Lab assessed. 3. Defined as freedom from >50% restenosis (Peak Systolic Velocity (PSV) ratio 2.0 as measured by duplex ultrasound) and no TLR.) SUPERB Results Safety and efficacy demonstrated with the Supera implant 1-year Results: Primary Patency (K-M) of 86.3% 1 Zero fractures 86.3% Significant improvement in ABI at 12 months versus baseline 2 and 89% of patients have improved more than 1 Rutherford- Becker clinical category at 12 months 2-year Results: 84% Freedom from TLR 0.5% fracture 3 8
Freedom From TLR 1/20/2015 Freedom From Clinically Driven TLR Through 3 Years 100% 80% 60% 40% 12 Months 89% 24 Months 84% Δ 3 years 7% 36 Months 82% 20% 0% 0 180 360 540 720 900 1080 Time Post Index Procedure (Days) Courtesy: Lawrence Garcia, MD, VIVA 2014 Supera Patency Rates DO NOT Appear to Decrease with Lesion Length 100% Percent Percent of Lesions of without Lesions Restenosis without by Lesion Restenosis Length (12 months SUPERB IDE Trial) by Lesion Length (12 months SUPERB TRIAL) 88% 88% 85% 50% 0% Shortest Lesions Middle Lesions Longest Lesions Shortest (35.4 ±12.3 Lesionsmm) Middle (73.5 Lesions ±10.8 (73.5±10.8cm) mm) (126.1 Longest ±33.4 Lesions mm) (35.4±12.3cm) (126.1±33.4cm) n=87 n=88 n=87 Courtesy: Lawrence Garcia, MD, VIVA 2014 SUPERB: Freedom From TLR Across Lesion Lengths is Fairly Constant 12 Months 24 Months 36 Months 100% 92 90 90% 88 83 84 81 82 81 79 80% 70% 60% 50% 40% 30% 20% 10% 0% Shortest Lesions Middle Lesions Longest Lesions Mean Lesion Length 35.4 mm 73.5mm 126.1 mm Min, Max Lesion Length 8.5, 55.0 mm 55.5, 91.5 mm 96.1, 236.4 mm Courtesy: Lawrence Garcia, MD, VIVA 2014 9
1/20/2015 SFA Patency Decreases with Lesion Length for PTA and Conventional Stenting but less so for Vascular Mimetic Implants Conventional PTA Nitinol Stents VMI/Supera Adapted from: Gray B. CCI. 2011 SUPERB: Outcomes in Severe Calcification Freedom From TLR (K-M) 100% 94.5 91.6 90% 87.6 80% 70% 60% 50% 40% 30% 20% 10% 0% 12 Months 24 Months 36 Months Superb Severe Calcification Subset Severe calcification 45% Patency (VIVA 1 year) 89% Severe Ca++ defined as1cm both sides vessel Courtesy: Lawrence Garcia, MD, VIVA 2014 SUPERB: Deployment Technique Impact on Freedom From TLR is Significant 100% 80% 90 90 90 91 87 87 12 Months 24 Months 36 Months 97 96 94 84 78 87 82 78 78 77 60% 63 40% 42 20% 0% Moderate Compression Minimal Compression Nominal Minimal Elongation Moderate Elongation Severe Elongation (21-40%) (11-20%) (±10%) (11-20%) (21-40%) (>40%) Courtesy: Lawrence Garcia, MD, VIVA 2014 10
1/20/2015 SUPERB: Essentially ZERO Stent Fracture Stent Fracture 12 Months 0.0% (0/236) 24 Months 0.5% (1/196) 36 Months 0.6% (1/162) Single Strut 0.0% 0.0% 0.0% Multiple Strut 0.0% 0.0% 0.0% Complete Fracture/Fragments 0.0% 0.5%* 0.6%* Aligned Complete Fracture/Fragments 0.0% 0.0% 0.0% Malaligned Spiral Fracture 0.0% 0.0% 0.0% * One subject experienced a Type III fracture at 24 months after 3 directional atherectomy procedures to treat in-stent restenosis. Courtesy: Lawrence Garcia, MD, VIVA 2014 In.Pact SFA Tepe, et al. Charing Cross 2014 DCB in SFA A New Therapy IN.PACT PTA p Paclitaxel DCB vs PTA Primary Patency (PSVR 2.4) 82.2% (157/191) 52.4% (54/103) <0.001 Clinically-driven TLR [1] 2.4% (5/207) 20.6% (22/107) <0.001 All TLR [2] 2.9% (6/207) 20.6% (22/107) <0.001 Primary Sustained Clinical Improv. [3] 85.2% (167/196) 68.9% (73/106) <0.001 ABI / TBI [4] 0.951 ± 0.221 0.886 ± 0.169 0.002 THUNDER: 5-Year Freedom from TLR Tepe, Zeller TCT 2011 Drug Eluting Stents Have Excellent Long Term Patency Approaching Bypass Patency(PSVR < 2.0): Provisional Zilver PTX vs BMS Courtesy: G. Ansel, MD 11
1/20/2015 Other Evolving Techniques: Atherectomy Devices DEFINITIVE LE Largest independently-adjudicated study of peripheral atherectomy performed to date (>800 patients) Claudicants Directional Atherectomy Primary Endpoint: Primary Patency at 12 Months (PSVR < 3.5) Secondary Endpoint: Orbital Atherectomy Primary Patency at 12 Months (PSVR < 2.4) Patency LL (cm) Patency LL (cm) All (n=743) 82% 7.5 78% 7.5 Diabetic (n=345) 80% 7.6 77% 7.6 Non-Diabetic (n=398) 83% 7.4 78% 7.4 Diabetics perform equally well when treated with directional atherectomy to non-diabetics for claudicants LASER Excisional/Aspiration McKinsey, JF, et al. JACC Cardiovasc Interv. 2014 Aug;7(8):923-33 Are we approaching equipoise in SFA revascularization? The 5-year primary patency of different types of conduits for the SFA Vein PTA/stents ~75% Femoral-popliteal 55-75% eptfe Graft 40-50% Surgical reconstruction Nitinol Stent Femoral-popliteal 60% (3-5year) 65-80% Femoral-tibial 60-75% Stent Graft 74% (1yr); 25% (3yr) VMI (Supera) >80% (1yr&3yr TLR) DES ~65-75% (5yr) DCB >70% (5yr) Atherectomy ~80% (1yr) AbuRahma et al, 1999; Green et al, 2000; Johnson and Lee, 2000; Klinkert et al, 2003; Saxon, JVIR 2013; McKinsey, JACC CI 2013; Ansel, TCT 2014; Zeller, TCT 2012 12
1/20/2015 Followup ABI 0.8 no symptoms ASA 81mg daily Plavix 75mg daily for 3 months (?) LLE asymptomatic Surveillance Duplex at 30d, 6mo, and 12 months and then annually Patent now out to 3 years Case 2: Bilateral Claudicant 66 yo salesman with Rutherford 3 claudication bilaterally R SFA heavily calcified subtotal occlusion requiring orbital atherectomy/pta/stent (overlapping 6x100 SE stents) L SFA CTO Occlusion treated next 13
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1/20/2015 Followup That patient has done well with stable and nearly normal ABI over 24 months We serial duplex surveillance demonstrates widely patent stents He is maintained on ASA Summary PTA and Conventional Nitinol Stents have relatively poor long term primary patency that worsens with lesion length Vascular Mimetic Implants are designed to resist the rigors of implantation within the SFA and have demonstrably improved primary patency and clinically driven TLR. Vascular Mimetic Implants are likely best suited to treat the majority of SFA lesions, particularly when calcification is present. Other emerging techniques including DES, DCB, and Atherectomy may have important roles in SFA Intervention VuMedi Webinar - Current Advances in SFA Interventions Cases and Applications of Bare Metal Stents and Vascular Mimetic Implants January 20, 2015 Sahil A. Parikh, M.D. Assistant Professor of Medicine Director, Research and Innovation Center Director, Experimental Interventional Cardiology Laboratory Director, Interventional Cardiology Fellowship Program Harrington Heart & Vascular Institute University Hospitals Case Medical Center Case Western Reserve University School of Medicine Cleveland, Ohio 19
Atherectomy for lower limb revascularization Lawrence A. Garcia, MD Chief, Section Interventional Cardiology and Vascular Interventions Director, Vascular Medicine St. Elizabeth s Medical Center Tufts University School of Medicine Boston, MA Case JC 2015 67 year old male with history HTN, HLP, CAD s/p PCI in the past and PVD with claudication Non-invasive work-up included ABI/duplex with ABI on the RLE 0.62 and duplex with serial lesions in the CFA/SFA and popliteal. Outflow appears preserved Angiography planned and images taken 1
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How would you treat this lesion? 3
Stenting? To date the current default technology is stenting To date the meaningful studies have evaluated 5-6 cm lesions and only 2 studies have tested long lesions closer to 20 cms that we consider real world cases The gorilla in the room is restenosis In-stent restenosis vs de-novo restenosis Focal vs diffuse Recurrent vs recurrent Alternative therapies have been shown to be just as durable and safe as DES/BMS and combination therapy appears very appealing B A Calcium C D Current endovascular data Patients (n) Device Lesion length (cm) 1 year primary patency (%) (PSVR) MIMIC 81 PTA NA NA ABSOLUTE 104 Stent 10.2 63 (2.5) RESILIENT 137 Stent 6.3 81 (2.4) VIBRANT 76 Stent graft 19.6 53 (2.5) VIPER 119 Stent graft 19.0 73(2.5) ZilverPTX 240 DES-SES 5.4 83 (2.0) THUNDER 54 DCB 7.4 74 (2.4) LEVANT 50 DCB 8.1 78 (2.5) IN-PACT 301/220 DCB 8.9 90 (2.4) 4
IN-PACT 2:1 randomized single blinded study DCB vs PTA alone 1 year results presented of 5 year study Lesions under 18 cm Occlusions under 10 cm RB 2-4 enrolled 331 randomized (all subjects) ITT 301 patients Provisional stenting listed in all subjects Baseline characteristics Lesion Type De-novo Restenotic Run off vessels 0 1 2 3 Prox popliteal involvement (%) IN-PACT PTA P n=220 subjects (221 lesions) 95.0% (209/220) 5.0% (11/220) 3.3% (7/212) 13.7% (29/212) 41.5% (88/212) 41.5% (88/212) n=111 subjects (113 lesions) 94.6% (105/11) 5.4% (6/111) 4.5% (5/112) 26.8% (30/112) 33.0% )37/112) 35.7% (40/112) 0.875 0.76 <0.05 0.15 0.34 6.8% (15/221) 7.1% (8/113) 1.00 Lesion length (cm) 8.94±4.89 8.81±5.12 0.81 Total occlusions (%) 25.8% (57/221) 19.5% (22/113) 0.22 Severe calcification (%) 8.1% (18/221) 6.2% (7/113) 0.66 RVD (mm) 4.65±0.84 4.68±0.83 0.73 MLD pre (mm) 0.90±0.78 0.93±0.77 0.71 Diameter stenosis pre (%) 81.1±15.5 81.3±13.7 0.95 All ITT, 12 month patency 5
Directional atherectomy SilverHawk Key Study Design Elements Study Design and Oversight: Prospective, non-randomized, global study 800 subjects enrolled at 47 centers CEC and Steering Committee oversight and CEC adjudicaiton Angiographic and Duplex core laboratory analyses Inclusion Criteria RCC 1-6 50% stenosis Lesion lengths up to 20cm Reference Vessel 1.5 mm and 7.0 mm Exclusion Criteria Severe calcification In-stent restenosis Aneurysmal target vessel Primary Patency in Subgroups Subgroup Claudicants (n=743) Patency (PSVR < 2.4) Lesion Length (cm) All (n=1022) 78% 7.5 By Lesion Length < 4 cm (n=318) 81% 2.2 4-9.9 cm (n=418) 83% 6.5 10 cm (n=283) 67% 14.4 SFA Only By Lesion Length < 4 cm (n=184) 78% 2.3 4-9.9 cm (n=253) 83% 6.5 10 cm (n=232) 65% 14.6 6
Effective treatment for all lesion lengths 12 Month Primary Patency Rates from DEFINITIVE LE 100% 90% 80% 70% 60% 81% 83% 67% 50% 40% PSVR < 2.4 30% 20% 10% 0% < 4 cm 4-9.9 cm 10 cm Mean length : 2.2 cm 6.5 cm 14.4 cm Number of lesions: 220 307 214 DEFINITIVE AR Study Design Purpose: assess and estimate the effect of treating a vessel with directional atherectomy + DCB (DAART) compared to treatment with DCB alone Registry arm for severely calcified lesions created to limit bail-out stenting (and therefore variables) in randomized arm. DAART* General and Angiographic Criteria Assessment Lesion severely calcified? No Yes Guidewire passage, enrollment & Randomization Guidewire Passage & Enrollment * Directional Atherectomy + Anti-Restenotic Therapy (N = 48) DCB (N = 54) DAART* (N=19) Baseline Lesion Characteristics Per Core Lab Baseline Characteristics DAART (N= 48) DCB (N = 54) p-value* DAART Severe Ca++ Arm (N=19) Lesion Length (cm) 11.2 9.7 0.05 11.9 Diameter Stenosis 82% 85% 0.35 88% Reference vessel diameter (mm) 4.9 4.9 0.48 5.1 Minimum lumen diameter (mm) 1.0 0.8 0.34 0.7 Calcification 70.8% 74.1% 0.82 94.7% Severe calcification 25.0% 18.5% 0.48 89.5% * p-value for DAART and DCB groups 7
Primary Patency Key Study Outcome at 12 Months Angiographic Patency shows similar pattern 100 90 80 70 60 50 40 30 20 10 0 90.9 82.4 71.8 68.8 58.3 42.9 All Patients Lesions > 10 cm All Severe Ca++ N = 34 N = 39 N = 22 N = 16 N = 24 N = 7 DAART DCB Results for all patients who returned for angiographic follow-up 12-Month Patency: DAART RCT Patients Is it Important to Achieve 30% Residual Stenosis with Directional Atherectomy Post-Procedure? 4.5 4 3.5 3 2.5 2 1.5 1 0.5 0 MLD = 4.27 0.92 2.16 0.23 1.61 1.39 0.96 0.78 DAART Arm ~15.1 mm 2 lumen p = 0.045 MLD = 3.78 DCB Arm ~11.8 mm 2 lumen area DCB DA Pre-Dilatation Baseline DAART resulted in a significantly larger area minimum lumen diameter (MLD) following the protocol-defined treatment in DEFINITIVE AR 100.0 90.0 80.0 70.0 60.0 50.0 40.0 30.0 20.0 10.0 0.0 90.0 77.8 DUS Patency 94.1 68.8 Angiographic Patency N = 20 N = 18 N = 17 N = 16 30% Residual Stenosis Post-DA >30% Residual Stenosis Post-DA Comparing non-stent technologies at 12 months 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Durability II IMPACT Fem-Pac Resilient Durability Levant 1 Supera Viper ZilverPTX Absolute Durability II Thunder Vibrant 78% 83% 68% DEFINITIVE LE Durability II 3 8 13 18 23 Lesion Length (cm) 8
Long lesion atherectomy Drug coated balloon technology is safe and effective IN-Pact has shown benefit at 1 year higher than any other trial to date in a level 1 randomized protocol at near 9 cm LL. DEFINITIVE LE proved atherectomy safe & effective at 12 months Effective for short, medium and long lesions in claudicants & CLI patients DEFINTIVE AR pilot study demonstrated a signal of benefit for combined therapy Initial signal suggests an potential role for DCB with atherectomy that may obviate the need for stenting as an upfront need for our patients with complex peripheral vascular disease Opportunity for re-therapy remains open to the operator and patient if no endoprosthesis is left behind at the index procedure. Overall cost benefit needs assessment but remember repeat revascularization for ISRS may not benign and only once 9