1. Fem-Pop Stenting: Is ZILVER PTX DES The “De Facto” Stent to Deploy?
IMPLANT
Krishna Rocha-Singh, MD
Chief Scientific Officer Prairie Heart Institute Saint John’s Hospital Springfield, IL

2. Krishna Rocha-Singh, MD
Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below.
Affiliation/Financial Relationship
Company
Grant/Research Support
Consulting Fees/Honoraria
Major Stock Shareholder/Equity
Royalty Income
Ownership/Founder
Intellectual Property Rights
Other Financial Benefit
None
Medtronic, Alucent, Zimmer-BioMet, ROX Medical,
PQ Bypass
Convergence Consulting, LLC
Yes
VIVA Board Member

3. Is Zilver PTX DES the De Facto IMPLANT to Deploy?
Lecture Goals:
Acknowledge the importance of well-designed RCTs/adjudicated registries in specific angiographic cohorts (i.e., long lesions, severely calcified).
Consider the importance of long-term clinical data to assess clinical utility of technologies.
Review recently released data from the REAL PTX RCT of Zilver PTX DES vs. DCB

4. VIVA SFA Nitinol Stent Meta-Analysis: Limitations/Caveats
Exploratory analyses of published data
full pre-specification not possible since trials well-known and published
Variation in definitions
Adds variability but may enhance generalizability of lesion length and ABI findings
However, large sample size helps to offset variability concern
Sample size constrained by available data (n=999)
Rocha-Singh et al, Cath Cardiovasc Interv, In Press

5. Lesion Length Association with Patency and CD-TLR at 12-mos
Patency and TLR Results by Lesion Tertile
Good slide relating patency, lesion length and TLR…was this CD-TLR?
UPDATED DATA
Rocha-Singh et al, Cath Cardiovasc Interv, In Press

6. Rocha-Singh et al, Cath Cardiovasc Interv, In Press

7. DUR II Baseline Lesion Characteristics: Impact of Time on Durability
Lesion length (mm) (Normal-to-Normal method)*
109.6 ± 45.0
Lesion length (mm) (20-to-20 method)§
89.1 ± 44.8
Pre-procedure diameter stenosis (%)
85.8 ± 16.2
Total Occlusion (%)
Mean occlusion lesion length (mm)§
48.1
102.7
Calcification (%)
None/Mild
30.0
Moderate
26.8
Severe
43.2
Rocha-Singh et al, Cath Cardiovasc Interv, 2015

8. Freedom from Loss of Primary Patency (PSVR < 2.0) at 3 Years
66.1%
77.9%
60.0%
287 Subjects
Freedom from loss of primary patency at 3 years was 60.0%
Rocha-Singh et al, Cath Cardiovasc Interv, 2015

9. Zilver PTX Drug-Eluting Peripheral Stent
Mechanical scaffold: Zilver Flex® Stent Platform
Drug therapy: Paclitaxel only
3 µg/mm2 dose density
No polymer or binder
PTX Coated
Uncoated

10. Drug-Eluting Technologies: How Do We Target Their Appropriate Use?
3-Yr adjudicated follow-up data in TASC II A-B lesions (mean lesion length 9.5cm, calcium-free) note a 83.5% freedom from CD-TLR rate
However, in longer (≥15 cm), calcified lesions (72%) provisional BMS use is required 40% to maintain a 1-yr freedom from CD-TLR of 94%
Adjunct use of ‘vessel prep’ devices to reduce provisional stent rates and improve DCB results have be hypothesized.

11. IN.PACT Global Long Lesion Imaging Cohort: Lesion/Procedural Characteristics
Lesions (N)
164
Lesion Type:
de novo
restenotic (no ISR)
ISR
83.2% (134/161)
16.8% (27/161)
0.0% (0/161)
Lesion Length
26.40 ± 8.61 cm
Total Occlusions
60.4% (99/164)
Calcification
Severe
71.8% (117/163)
19.6% (32/163)
RVD (mm)
4.594 ± 0.819
Diameter Stenosis (pre-treatment)
90.9% ± 14.2
Dissections: 0
37.9% (61/161)
A-C
47.2% (76/161)
D-F
14.9% (24/161)
Device Success [1]
99.5% (442/444)
Procedure Success [2]
99.4% (155/156)
Clinical Success [3]
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)
Given the provisional BMS use in complex SFA lesion morphologies, should primary DES deployment be considered the primary ‘de facto’ strategy?
Device success: successful delivery, inflation, deflation and retrieval of the intact study balloon device without burst below the RBP
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)
Clinical success: procedural success without procedural complications (death, major target limb amputation, thrombosis of the target lesion, or TVR) prior to discharge
M. Jaff VIVA 2016

12. REAL PTX Study Design A Pilot Study
Prospective, multicenter (5 EU sites), randomized, controlled trial
Zilver PTX DES vs DCB (~90% In.PACT Admiral) (1:1) in native FP disease
N= 150 patients, 75 in each group
Stratification for lesion length for both groups (1:1:1)
short: ≤ 10 cm
middle: > 10 and ≤ 20 cm
long: > 20 and ≤ 30 cm
Mean lesion length: 15.3 ± 8.8 cm
Independent angio and DUS core lab adjudication
D. Scheinert, LINC 2017

13. Study Design
Follow-up: 3-Years Endpoints: - Primary: Primary 12 Month (Duplex) - Secondary: Procedural sucess Major Adverse Event (Major Amputation; Death or TLR within 30 days) Primary 24, 36 Month Clinically-driven target lesion revascularization (TLR) ABI, Improvement in Rutherford Categories, Walking capacity (WIQ)
D. Scheinert, LINC 2017

14. Randomized and stratified (n=150)
Patient Flow Chart
Randomized and stratified (n=150)
DCB (n=75)
DES (n=75)
Short (n=25)
Mid (n=26)
Long (n=24)
Mid (n=24)
Long (n=26)
death = 5, withdrawal = 2, missed visit = 1
6 MFU (n=132)
12 MFU (n=122)
24 MFU(n=113)
withdrawal =2, lost = 1, missed visit= 3
withdrawal =3
death = 3, withdrawal = 4, lost = 2
death = 2, withdrawal = 6, lost = 1, missed visit = 1   
withdrawal = 5, lost = 1 
Was any pt randomised to DEB excluded, due to bad PTA???
D. Scheinert, LINC 2017

15. Lesion Characteristics
DCB (n=75)
ZilverPTX (n=75)
*p-value
Claudication (RC 2-3), n (%)
67 (89.3)
63 (84.0)
Critical limb ischemia (RC 4-5), n (%)
8 (10.7)
12 (16.0)
0.472
Target lesion length (mm) ± SD*
144.8 ± 92.1
159.6 ± 97.3
0.341
Lesion location, n (%)***
SFA
60 (80.0)
Popliteal affected
15 (20.0)
0.524
Occlusion, n (%)***
40 (53.3)
39 (52.0)
0.870
MLD in lesion, mm ± SD
0.57 ± 0.77
0.66 ± 0.77
0.571**
Percent diameter stenosis, %
87.4 ± 16.8
86.9 ± 15.2
0.745**
Lesion calcification, n (%)
0.561
None
19 (25.3)
16 (21.3)
Mild
22 (29.3)
Moderate
2 (2.7)
4 (5.3)
Moderately severe
17 (22.7)
Severe
26 (34.6)
No mention on the 50% severe calcification on other slides – consider adding to slide 17
*Fisher‘s exact test is performed in general, ** non-parametric test (Mann-Whitney-Wilcoxon-U using t approximation)
*** Satterthwaite approximation should be generally used (no deviations in all other variables)
D. Scheinert, LINC 2017

16. Acute Outcome D. Scheinert, LINC 2017 DCB (n=75) ZilverPTX *p-value
Provisional stenting Core Lab, n (%)
19(25.3) NA
Residual Stenosis:
Visual estimate ≥ 30%, n (%)
2 (2.7)
1 (1,3)
Core Lab > 30%, n (%)
14 (18.7)
30 (40.0)
< 0.001*
MLD post-procedure, mean ± SD
3.5 ± 0.7
4.1 ± 0.7
< 0.001
Dissection, n (%)
54 (72.0)
29 (38.7)
Type A/B, n (%)
19 (25.3)
11 (14.7)
Type C-F, n (%)
35 (46.7)
18 (24.0)
Complication
Embolic event, n (%)
4 (5.3)
1 (1.3)
AV-Fistel (local), n (%)
6 (8.0)
Target Vessel Perforation, n (%)
* For comparison Fisher‘s exact test is performed in general
D. Scheinert, LINC 2017

17. 1° Patency @ 12 and 24 months Primary Patency D. Scheinert, LINC 2017
risk
(n)
DCB (75) 64 48 29
DES (75) 63 33
1° Patency
(%)
DCB
87.6
1.00
76.2
0.96
49.4
0.78
DES
58.2
D. Scheinert, LINC 2017

18. Significant Loss of 1° Patency in Lesions >20 cm
Drug Coated Ballon (ITT)
Zilver PTX
Primary Patency
Consider adding arrows on both- see next slide.
Stratified
1° 24 Month (%) 1
<= 10cm
76.1 2
> 10cm and <= 20cm
40.0 3
> 20 cm and <= 30cm
33.1
Stratified
1° 24 Month (%) 1
<= 10cm
78.4 2
> 10cm and <= 20cm
56.7 3
> 20 cm and <= 30cm
43.2
* p was calculated using log rank test
D. Scheinert, LINC 2017

19. Residual Stenosis ≥ 30%
Acute Outcome
DCB
(n=75)
ZilverPTX
*p-value
Residual Stenosis
Visual estimate ≥ 30%, n (%)
2 (2.7)
1 (1.3)
Core Lab > 30%, n (%)
14 (18.7)
30 (40.0)
< 0.001*
Optimize acute outcome with consistent vessel preparation  may potentially lead to better long-term patency
Consider adding; emerging evidence suggests this will influence longer term patency
Vessel prep is a big thing for LINC
D. Scheinert, LINC 2017

20. Fem-Pop Stenting: Is ZILVER PTX DES The “De Facto” Stent to Deploy?
REAL PTX randomized controlled pilot trial results illustrates several points: --- All RCTs are not created equal --- “Vessel prep” and uniform deployments techniques both DCBs and Zilver PTX are essential --- Additional analysis of the ‘mode of failure’ should provide additional insights --- Cost considerations in technology choice must be assessed in future trials