1. Eric J Dippel, MD FACC Davenport, Iowa, USA February 19, 2017
What is the Ideal Treatment Strategy for Fem-Pop In-Stent Restenosis: Laser, DCB, DES, or Covered Stent?
Eric J Dippel, MD FACC
Davenport, Iowa, USA
February 19, 2017

2. Conflict of Interest Consultant Shareholder Abbott Vascular Bard
Boston Scientific
Covidien
Medtronic
Spectranetics
WL Gore
Shareholder

3. Global PAD/ISR Scope of Problem
>200M People Living with PAD Globally
<2% Treated Surgically or Endovascularly
>400,000 FemPop Stents Implanted WW Every Year
250,000 ISR Cases
U.S. ISR Incidence
>200,000 Stents / Year implanted
Stent volume growing 6-7% annually
30-40% 1st time ISR Incidence within 2 years of implant ,000 US ISR Cases

4. Histology Neointimal hyperplasia 15% cellular 85% extracellular matrix
Very high water content

5. EXCITE ISR Trial Overview
DESIGN:
Prospective, randomized, multi-center clinical evaluation of excimer laser atherectomy (ELA) for ISR
Primary Safety Endpoint:
Major Adverse Events (MAE) during hospitalization through 37-day follow-up to include all death, unplanned major amputation, or target lesion revascularization
Primary Effectiveness Endpoint:
Freedom from clinically driven TLR through 6 month follow-up (212 days)
252 patients enrolled between June 2011 and March 2014 in 40 clinical sites in US
7 lesions uncrossable
252 lesions crossable by guidewire
170 ELA + PTA
82 PTA
Primary Safety endpoint at 37 days (n=158)
Primary Safety endpoint at 37 days (n=77)
Primary Efficacy endpoint at 212 days (n=157)
Primary Efficacy endpoint at 212 days (n=73)
Dippel et al. JACC CI. 2015;8:92-101

6. Baseline Lesion Characteristics
Angiographic Core Lab Assessment
ELA + PTA
(N=169)
PTA Alone
(N=81)
P-value
Mean Lesion Length (cm)
19.6
19.3
0.85
Diameter Stenosis (%)
81.7%
83.5%
0.42
Popliteal Lesion
21.3% 
23.4% 
0.93
Total Occlusion
30.5%
36.8%
0.37
Calcium (Mod/Sev)
27.1%
9.1%
0.005
Stent Fracture
0.16
85.8%
95.8% 1
5.0%
0.0% 2
6.4%
4.2% 3
2.1% 4 5
0.7%
20% of lesions were > 30 cm in length
Dippel et al. JACC CI. 2015;8:92-101

7. Product-Limit Survival Estimates
Freedom from TLR
Survival Probability
Product-Limit Survival Estimates
With number of subjects at risk
Days from Index Procedure
p < 0.003
365
Dippel et al. JACC CI. 2015;8:92-101

8. Product-Limit Survival Estimates
Freedom from MAE
Survival Probability
Product-Limit Survival Estimates
With number of subjects at risk
Days from Index Procedure
p < 0.001
365
Dippel et al. JACC CI. 2015;8:92-101

9. Variable (Lesion Length)
Lesion Length and TLR
Favors ELA & PTA
Favors PTA
Variable (Lesion Length)
Estimate
Lower CL
Upper CL
5 cm
0.96
0.43
2.14
15 cm
0.66
0.39
1.12
25 cm
0.46
0.29
0.70
35 cm
0.31
0.17
0.58
Risk Estimate
Dippel et al. JACC CI. 2015;8:92-101

10. DEB Experience in SFA ISR
3 Prospective Registries
IN.PACT SFA ISR
DEBATE-ISR
PLAISIR
4 Prospective Randomized Control Trials
PACUBA
FAIR
COPA CABANNA
ISAR-PEBIS—on going

11. PACUBA study Prospective Randomized 1:1 Single center N = 60 (planned)
EuroCor balloon
No core lab
Lammer J, et al. Veith. 2011

12. FAIR study Prospective Multi-center Primary end pt binary restenosis
IN.PACT balloon
Ave length 82 mm
Core lab
Krankberg H, et al. LINC 2015

13. COPA COBANNA study Prospective Multi-center
Primary end point LLL by DSA
N = 88
Cotavance balloon
Ave length 119 mm
Core lab
Krankberg H, et al. LINC 2015

14. Zilver PTX Global Registry

15. Zilver PTX Global Registry

16. 100 patients enrolled in 7 clinical sites in Europe
RELINE Trial Overview
DESIGN:
Prospective, randomized, multi-center clinical evaluation of Viabahn for ISR
Primary Safety Endpoint:
Major Adverse Events (MAE) during hospitalization through 30 day follow-up to include all death, unplanned major amputation, or target lesion revascularization
Primary Effectiveness Endpoint:
Primary patency at 12mth, PSVR>2.5
100 patients enrolled in 7 clinical sites in Europe
47 Viabahn
53 PTA
8 Excluded
9 Excluded
39 pts analyzed
44 pts analyzed
Deloose K. LINC 2014

17. RELINE Demographics and Lesion Characteristics
Deloose K. LINC 2014

18. RELINE Efficacy
Safety non-inferior
Deloose K. LINC 2014

19. General & Angiographic Screening Lesion gradient <15mmHg
SALVAGE Study Design
Femoropopliteal artery in-stent restenosis (ISR)
Prospective registry
9 US sites
Anticipated enrollment 100 pts
Actual enrollment 27 pts
Enrolled
Viabahn
Yes
General & Angiographic Screening
ELA + PTA
Lesion gradient <15mmHg
No Viabahn
Screen failure No
Primary endpoint 12mth patency
Laird et al. Cath Card Interv. 2012;80:

20. 2 mm Turbo Elite laser pilot channel
8 Fr Turbo Booster sheath
6x100 PTA
3mmHg gradient
6x150, 6x50 Viabahn

21. Photo PAC study Prospective Single-center
Primary end pt binary restenosis
N = 14
Laser atherectomy
IN.PACT balloon
Ave length 133 mm
Mean f/u 19 mths
Duplex PSVR>2.4
No core lab
One pt had restensois and TLR at 36 mths
Van den Berg J et al. J Invas Card. 2014;26(7):

22. Conclusions A new paradigm is emerging for the treatment of FemPop ISR
PTA alone has failed against 3 different treatment strategies
DCB is effective for lesions less than 10cm
More data is needed for Tosaka 3, cost effectiveness
DES is effective for moderate length lesions
Not FDA approved
Both laser atherectomy and Viabahn are effective for long lesions
Both are FDA approved for ISR
Combination therapy needs further investigation