1. The (Potential) Role of Drug Eluting Balloons in BTK Interventions
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, 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
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, Medtronic, Spectranetics, Terumo, TriReme, Volcano

3. DEB are not yet indicated in clinical routine
Further Research needed!
Why?

4. Conflicting Evidence DEBATE BTK vs. IN.PACT Deep
Journal of the American College of Cardiology ;15:
Drug-Eluting Balloon Versus
Standard Balloon Angioplasty for
Infrapopliteal Arterial Revascularization in Critical Limb Ischemia
12 Month Results From the IN.PACT DEEP Randomized Trial
Thomas Zeller, Iris Baumgartner, Dierk Scheinert, Marianne Brodmann, Marc Bosiers, Antonio Micari, Patrick Peeters, Frank Vermassen, Mario Landini, David B. Snead, K. Craig Kent, Krishna J. Rocha-Singh, IN.PACT DEEP Trial Investigators
Circulation
Drug-Eluting Balloon in peripherAl inTErvention for Below The Knee Angioplasty Evaluation (DEBATE-BTK): A Randomized Trial in Diabetic Patients with Critical Limb Ischemia
Single-Center Randomized Trial
132 Patients
CLI: 100%, Diabetes: 100%
Average lesion length: 13 cm
CTO: 80%
IN.PACT™ Amphirion™ vs. PTA ™
Liistro F et al. Drug-eluting balloon in peripheral intervention for below the knee angioplasty evaluation (DEBATE-BTK): a randomized trial in diabetic patients with critical limb ischemia. Circulation Aug 6;128(6):615-21
T. Zeller LINC 2014 & Zeller et al. JACC 2014

5. Binary Restenosis (BR) and Clinically Driven TLR (CD-TLR)
IN.PACT Deep
12-month Freedom from Major Amputation, Binary Restenosis Rate, TLR Rate & LLL
12-month
Binary Restenosis (BR) and
Clinically Driven TLR (CD-TLR)
12-month
Late Lumen Loss
0.605
± 0.775
0.616
± 0.781
Zeller T. et al. JACC 2014

6. IN.PACT DEEP vs. CLI literature
Lowest Restenosis, TLR and Major Amputation in both arms
IN.PACT DEEP
[1] Rocha-Singh KJ et al. Catheter Cardiovasc Interv Nov 15;80(6): ; [2] Bosiers M LINC 2011; [3] Zeller T. LINC 2011; [4] Scheinert LINC 2011
«amputations»
[1] Lejay A et al. Acta Chir Belg. 2009; [2] Romiti M et al. J Vasc Surg. 2008; [3] Adam DJ et al. Lancet. 2005; [4] Rocha-Singh KJ et al. Catheter Cardiovasc Interv. 2012; [5] Scheinert D et al. JACC 2012; [6] Iida et al. EJVEVS 2012

7. 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)

8. DEB-BTK - Negative Evidence: BIOLUX P II
72-patients (CLI + IC) RCT of Passeo-18 Lux vs. PTA
12-month CD-TLR Rates:
30.1% (DCB) vs. 30.6% (PTA)
(p=0.805)
12-month Loss of Primary Patency
49.2% (DCB) vs. 45.6% (PTA)
(p=0.908)
Event Rate: TLR Lesions
0.0%
20%
40%
60%
80%
100%
Time to Event (days)
365
uncoated
DRB
Event Rate: Patency loss
0.0%
20%
40%
60%
80%
100%
Time to Event (days)
365
uncoated
DCB
Amputation target extremity
Major
8/ 23.7 [12.6,42.0]
1/ 3.3[0.5,21.4]
9/ 25.8 [ 14.3, 43.9]
2/ 5.6 [1.4,20.7]
0.975
0.631
Zeller T et al., JACC CCI 2015

9. Why do we need deb in btk interventions?

10. In CLI most BTK lesions are longer than 10cm
Bare metal stents did fail to show a benefit over PTA

11. Ferraresi R, LINC 2016

12. In CLI most BTK lesions are longer than 10cm
Bare metal stents did fail to show a benefit over PTA
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

13. Why do we need deb in btk interventions?
Because Patency matters!

14. Ferraresi R, LINC 2016

15. Liistro F et al. Drug-eluting balloon in peripheral intervention for below the knee angioplasty evaluation (DEBATE-BTK): a randomized trial in diabetic patients with critical limb ischemia. Circulation Aug 6;128(6):615-21

16. Ulcer Healing & Ambulation and Vessel Patency

17. Vermassen F, LINC 2016

18. Vermassen F, LINC 2016

21. 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.

22. Wound Healing & Preserved Pedal Arch

23. NO DCB Class Effect?! results awaited
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

24. 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 1315 cm
Inpact Deep is the 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 DEB vs. PTA at 12-month FU
underpowered study
No difference in amputation rates
No major differences in hard clinical outcomes across all studies between any DCB and control

25. DEB in BTK Interventions Summary II
Further research on the efficacy of DEB in tibial arteries is mandatory
1. step: Due to potential safety concerns regarding the cytotoxic drug paclitaxel efficacy studies should include claudicants only, no wounds
Angiographic primary endpoint, e.g. LLL, binary restenosis
2. step: clinical endpoint driven CLI study after confirmation of biological efficacy of paclitaxel eluting DEB in tibial arteries
Alternative exipients resulting in higher drug uptake of paclitaxel
Reduction of overall drug dose (paclitaxel)
Alternative antiproliferative, non-toxic drugs in CLI patients
“Limus” drugs

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