Making BTK Interventions more Durable: Are DES and DCB the answer? Thomas Zeller, MD

Transcription

1 Making BTK Interventions more Durable: Are DES and DCB the answer? Thomas Zeller, MD

2 Faculty Disclosure Thomas Zeller, MD For the 12 months preceding this presentation, I disclose the following types of financial relationships: Honoraria received from: Abbott Vascular, Angioslide, Bard Peripheral Vascular, Veryan, Biotronik, Boston Scientific Corp., Cook Medical, Cordis Corp., Covidien, Gore & Associates, Medtronic, Spectranetics, Straub Medical, TriReme, VIVA Physicians Consulted for: Abbott Vascular, Bard Peripheral Vascular, Boston Scientific Corp., Cook Medical, Gore & Associates, Medtronic, Spectranetics, ReCor Research, clinical trial, or drug study funds received from: 480 biomedical, Bard Peripheral Vascular, Veryan, Biotronik, Cook Medical, Cordis Corp., Covidien, Gore & Associates, Abbott Vascular -DEV Technologies, Inc., Medtronic, Spectranetics, Terumo, TriReme, Volcano

3 BTK Restenosis and TLR rates post-pta Insufficient Durability 101 Patients 12m Angio 60 Patients 10m Angio 33 Patients 6m Angio 11 Patients 12m Angio 67 Patients 12m Angio 58 Patients 3m Angio PTA arm PTA arm PTA arm 1. D.Scheinert, J Am Coll Cardiol 2012;60:2290 5) 2. H.K.Soder, J Vasc Interv Radiol 2000; 11: F. Baumann, J Vasc Interv Radiol 2011; 22: F.Fanelli, J Endovasc Ther. 2012;19: F.Liistro, TCT 2012 oral presentation 6. A.Schmidt, Catheter Cardiovasc Interv Dec 1;76(7):

4 Multicentre Study PTA vs. carbofilm coated Stents in infrapopliteal arteries 59 patients; 95 lesions: 53 PTA, 42 stents 6 months follow-up with CT-angiography: p<0.05 Survival distribution Function Restenosis > 70% PTA Stent Days Rand T et al., Cardiovasc Interv Radiol. 2006

5 YUKON/DESTINY/ACHILLES 12-month primary patency P < 0.05 For all trials Rastan et al. EHJ 2011 Bosiers et al. JVS 2011 Scheinert et al. JACC 20

6 YUKON-BTK Trial: Event-free Survival at 24 months Survival free from TVR, major and minor amputation, myocardial infarction and death was compared by Kaplan-Meier analysis with the use of the Mantel-Cox log-rank test Rastan A. et al. JACC 2012

7 MAE and Limb salvage at 2-year FU in patients with CLI DES vs. BMS (YUKON Trial, Rastan A. et al. JACC 2012) CLI cohort Sirolimus Stent (N=38) Bare Metal Stent (N=31) P Death 10 (26.3%) 10 (30.3%) 0.60 Major-/Minor Amputation 1/1 (5.3%) 4/3 (22.6%) 0.04 TVR 4 (10.5%) 4 (12.9%) 0.70 Myocardial infraction 0 (0%) 2 (6.4%) 0.20 Limb salvage 37 (97.4%) 27 (87.1%) 0.10 Rastan A. et al. JACC 2012

8 DES vs. PTA in BTK (RCT) ACHILLES [1-2] randomized Trial Cypher Select vs. PTA Lesion length 2.7 cm (DES) / 2.7 cm (PTA) 12-m TLR = 10.0% (DES) vs. 16.5% (PTA) (p=0.257) 12-m Wound Heal. Rate (WHR): 61.7% (DES) vs. 41.3% (PTA) (p=0.0628) 39% TLR p= % WHR p= D.Scheinert et al. A Prospective Randomized Multicenter Comparison of Balloon Angioplasty and Infrapopliteal Stenting With the Sirolimus-Eluting Stent in Patients With Ischemic Peripheral Arterial Disease. (J Am Coll Cardiol 2012;60: Konstantinos Katsanos CIRSE 2012 Oral Presentation

9 MAE and TVRat 2-year FU in patients with Claudication DES vs. BMS (YUKON Trial, Rastan A. et al. JACC 2012) Intermittent Sirolimus Stent (N=38) Bare Metal Stent (N=44) P claudication Death 7 (18.4%) 8 (18.2%) 1.0 Major-/Minor Amputation 0/0 (0%) 0/2 (4.7%) 0.19 TVR 3 (7.9%) 11 (25%) 0.04 Myocardial infraction 1 (2.6%) 2 (4.5%) 0.50 Limb salvage 31 (100%) 36 (100%) 1.0 Rutherford-Becker class Median change (IQR) -1 (-2 to -1) -1 (-1 to 0) 0.03

10 Limitation of Long BTK-Lesions Balloon-angioplasty Residual stenosis Focal stenting with DES Follow-up

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13 DES in BTK Lesion Trials Summary & Limitation In lesions up to 10cm DES are the treatment of choice in BTK lesions extending to the ankle They are superior to BMS and POBA Longest lesions enrolled in ACHILLES (up to 10cm) Uncertainty about the performance of DES in long lesions Improved patency after DES results in Reduced TLR rates Preserved clinical benefit Increased limb preservation Rastan et al. EHJ 2011; Scheinert et al. JACC 2012; Bosiers et al. JVS 2012

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15 DEB are not yet indicated in clinical routine Further Research needed!

16 DEB-BTK - Negative Evidence: IN.PACT DEEP Rigorous 358-patient RCT (IN.PACT Amphirion vs. PTA) T. Zeller LINC 2014 & Zeller et al. JACC 2014

17 DEB-BTK - Negative Evidence: IN.PACT DEEP Failure to meet Primary Efficacy Endpoint T. Zeller LINC 2014 & Zeller et al. JACC 2014

18 DEB-BTK - Negative Evidence: IN.PACT DEEP Trend towards higher Major Amp. Rate in DEB arm T. Zeller LINC 2014 & Zeller et al. JACC 2014

19 DCB-BTK Evidence: DCB vs. DES 50-patients (CLI + IC) RCT of IN.PACT Amphirion vs. DES Lesion length: 14.8 (DCB) vs (DES) (p=0.330) Key findings (DCB vs. DES) at 6- month: Binary restenosis: 58% vs. 28% (p=0.0457) LLL: 1.35±0.2 vs. 1.15±0.3 (p=0.62) >50% restenosis length (cm): 4.3±1.6 vs. 3.6±1.5 (p=0.16) TLR: 14.3% vs. 7.4 (p=0.21) (P.M. Kitrou, MD, PhD CIRSE 2013, LINC 2014)

20 WHY DO WE NEED DEB IN BTK INTERVENTIONS?

21 Why do we Need DEB in BTK Interventions? In CLI most BTK lesions are longer than 10cm No dedicated DES for BTK use are yet commercially available and clinically tested Appropriate length, at least 8cm for balloon expandable stents Drug eluting nitinol stents not yet tested below the knee Are stents the right choice for long distant BTK lesions extending to the foot? DEB are the optimal treatment tool for long BTK lesions an din particular foot arteries

22 Wound Healing & Preserved Pedal Arch

23 Background of Pedal Artery Interventions Due to the small vessel diameters and extensive external forces exposed to the distal tibial and pedal arteries stents in particular DES are no option for improving durability of the procedure. Thus, DEB is an interesting choice.

24 NO DCB Class Effect IN.PACT DEEP failure applies to IN.PACT Amphirion only. Each DCB stands on the merits of its own data 480-patient RCT of Lutonix DCB vs. PTA in BTK-CLI results awaited Marianne Brodmann LINC 2014

25 DEB in BTK Interventions Summary I Early DCB-BTK evidence showed high promise for IN.PACT Amphirion to reduce restenosis and reintervention rates at 3 and 12 months vs. PTA Significantly higher restenosis rates reported for IN.PACT Amphirion vs. DES vs. in BTK lesions with length cm Inpact Deep is the first and largest BTK-CLI Trial completed to date Failed to demonstrate superior treatment effect of IN.PACT Amphirion vs. PTA Met primary safety endpoint; safety signal detected with a trend toward higher major amputation rate in the DCB arm No significant difference primary patency with Passeo 18 Lux vs. PTA at 6-month FU underpowered study No difference in amputation rates No major differences in hard clinical outcomes across all studies between any DCB and control

26 DEB in BTK Interventions Summary III For foot arteries and distal tibial arteries DEB need a coronary balloon like profile DEB coating must be hydrophilic High friction of the drug coating in small & calcified arteries The combination of atherectomy and DEB should be considered in calcified BTK lesions To reduce friction To reduce recoil To potentially improve drug uptake / wall persistance

27 Making BTK Interventions more Durable: Are DES and DCB the answer? Thomas Zeller, MD