1. Bare Metal Stent Self Expandable Stent Balloon Expandable Stent

2. Balloon-Expandable Stents – Overview
Formula
Formula 414 RX Vascular
Formula 418 Vascular
Formula 535 Vascular

3. Balloon-Expandable Stents – Overview

4. Zilver Stent with history and development
2009:
Launch of
Zilver PTX 7 Fr
2004:
Launch of Zilver 635
2009:
Launch of Zilver Flex
2011:
Launch of
Zilver PTX 6 Fr
2003:
Launch of Zilver 518
2008:
Launch of Zilver 518RX
2015:
Launch of New delivery system Zilver PTX
2011:
Launch of
Zilver Vena
2001:
Launch of Zilver 735
Zilver 735 obsoleted
Zilver PTX Thumbleweel 2015
2000
2015

5. Nitinol Nickel Titanium Naval Ordinance Laboratory Superelastic alloy
Memory shape material
Has lowest fatigue-crack growth resistance of metallic alloys used for implant
Ni Ti N O L
Nitinol is an alloy between Nickel and Titanium

6. BES vs. SES

7. Open Cell vs. Closed Cell
Open Cell: - More flexible
- Conforms to vessel wall better
- Less metal in smaller vessels
Closed Cell: - More radial force
- Greater plaque coverage
All Cooks zilver stents platform is with Open Cell design.
Tanaka N, Martin JB, Tokunaga K, et al. Conformity of carotid stents with vascular anatomy: evaluation in carotid models. AJNR Am J Neuroradiol. 2004; 25(4):
Silva M. Debate: open cell stents are superior! Presented at: ICCA V 5th International Course on Carotid Angioplasty and Other Cerebrovascular Interventions; October 28, 2005; Frankfurt, Germany.

8. Zilver® Flex™35 - Box

9. Zilver Flex 35
Linear connectors result in more uniform load distribution and more stable deployment characteristics (no twisting or elongation)
Even though we designed more tie bars we did not compromissed with the flexibility

10. Zilver Flex 35
Tie-bar connectors alternate direction resulting in enhanced axial fatigue
And still provids better result for enhancing the axial (compression) fatigue/fracture rate.

11. Physician Preferences Self-Expandable Stent
When to use what?
Physician Preferences
Self-Expandable Stent
Balloon-Expandable Stent
SES and BES are perfect substitutes
Explain that from a sales perceptive – it is always the physicians preferences this the most important.
We do not mind if he use a SX or BX stent.

12. When to use what?
BES: “The high radial strength of the balloon expandable stents and the lack of foreshortening make them suitable, in particular, for ostial or severely calcified lesions."
Source: Manual of peripheral vascular intervention, Casserly, I. P. et al., 2005 by Lippincott Williams & Wilkins, USA
Common iliac

13. When to use what?
SFA
Se ”Papir”

14. Zilver PTX

15. The Only Drug Eluting Peripheral Stent for the SFA
Backgound
Launched in Europe in 2009
More than 250,000 patients treated
Sold on 6 continents
5 year clinical data follow-up
Late 1980s: Cook starts working on DES in the with coronary stents
Mid 1990s: Cook begins working on paclitaxel-coated coronary DES
Demonstrated effectiveness in two clinical studies (ASPECT and ELUTES) using a similar polymer-free paclitaxel coating as that on the Zilver PTX
ASPECT: Randomized Clinical Study with approximately 60 patients each with bare metal and paclitaxel-coated Supra G stents. Effectiveness clearly demonstrated with 6-month restenosis rates of 27% and 4%, respectively
ELUTES: Randomized Clinical Study with approximately 40 patients each with bare metal and paclitaxel-coated V-Flex Plus stents. Effectiveness clearly demonstrated with 6-month restenosis rates of 21% and 3%, respectively
Obtained CE Mark and commercialized the V-Flex Plus PTX coronary stent in Europe
2000 Devt work ZPTX, Randomized 2005
2012: Japan(1)/USA(2)
Proven Drug Effect

16. Mechanical Therapy: Established Technology
Stent Platform
Zilver® PTX® is based on the next-generation Zilver Flex stent platform
The stent is known for its balance of flexibility, fracture resistance, and radial force
The combination of drug-elution and a strong yet flexible scaffold is the standard of care for SFA lesions

17. Drug Therapy: Paclitaxel coating (PTX)
Zilver PTX Drug-Eluting Peripheral Stent
New generation SFA Stent
Available in over 50 countries
Approved in EU, Japan, and US
Scaffold plus drug
Mechanical scaffold: Zilver Flex® Stent Platform
Drug therapy: Paclitaxel only
No polymer or binder
3 µg/mm2 dose density
Uncoated
PTX Coated

18. Why Are Drugs Used? To reduce restenosis
To inhibit smooth muscle cell proliferation
Reduce inflammation

19. X Paclitaxel Natural substance from the bark of (Taxus Brevifolia)
Western Yew tree
Originally developed and used as a cancer drug to stop cell proliferation X

20. Mechanism of Action Normal cell cycle PTX effect on cell cycle
A normal cell cycle is when a cell replicates into two new cells.
PTX effect on cell cycle
Paclitaxel stops the cell cycle in phase M (mitosis) and therefore prevents the cell from replicating into two new cells

21. Why we need drug-eluting devices?
Paclitaxel (PTX) permanently prevents cell division
Reduces restenosis
Inhibits smooth muscle cell proliferation
Reduces inflammation

22. Intended use
The Zilver PTX Drug Eluting Peripheral Stent is intended for use in the treatment of…
symptomatic vascular disease of the above-the-knee femoropopliteal arteries
having reference…
vessel diameter from 4 mm to 7 mm.
To avoid involvement of the common femoral artery, the proximal end of the stent should be placed…
at least 1 cm below the origin of the superficial femoral artery.
To avoid involvement of the below-the-knee popliteal artery, the distal end of the stent should be placed…
above the plane of the femoral epicondyles.
The intended use for Zilver PTX is for the treatment of de novo or restenostic symptomatic lesions in the above the knee fempop arteries.
The preliminary sizes available will be for lesions 4-6 mm in diameter and lengths up to 140 mm per limb and 280 mm per patient.
(Vessel size 4-6 mm of SFA)

23. Stent sizing
Sizing recommendations are similar to standard bare metal stents.
Measure the diameter of the reference vessel (proximal and distal to the lesion) and use the largest reference diameter as your basis for choosing the appropriate stent size.
The stent size should be selected so that the unconstrained stent diameter is at least 1 mm larger than the reference vessel diameter and no more than 2 mm larger than the reference vessel diameter.
Stent sizing can be determined exactly as you would for BMS by measuring the RVD and upsizing the stent at least 1 mm larger and no more than 2 mm larger than it.

24. Available product configurations
Stent diameters
5, 6, 7 and 8 mm
Stent length
40, 60, 80, 100 and 120 mm
Delivery system
6 Fr
Delivery system length
80 cm and 125 cm
Cook wants to make Zilver PTX available to as many patients as possible. Therefore, initially, only two sizes will be available to work with supplying the demand. That will be the 6 x 80 and the 7 x 80 on a 6 Fr, 125 cm delivery system. We will continue to expand the sizes as we move forward. (40, 60 mm lengths, 8 mm diameter, longer lengths)

25. Zilver PTX - Superior Results

26. Zilver PTX – two key trials
RCT: 2005
SAT: 2006

27. 5-year Freedom from TLR Zilver PTX vs. Standard Care
83.1%
Zilver PTX
p < 0.01
log-rank
Optimal PTA + BMS
67.6%
At 5 years, Zilver PTX demonstrates a 48% reduction in reintervention compared to standard care

28. 5-year Primary Patency (PSVR < 2.0) Zilver PTX vs. Standard Care
66.4%
Zilver PTX
p < 0.01
log-rank
Optimal PTA + BMS
43.4%
At 5 years, Zilver PTX demonstrates a 41% reduction
in restenosis compared to standard care

29. 5-year Primary Patency (PSVR < 2.0) Zilver PTX vs. Standard Care
66.4%
Zilver PTX
Optimal PTA + BMS
43.4%
From 1-5 years, the relative
separation increases by 35%

30. 5-year Freedom from TLR Provisional Zilver PTX vs. BMS
84.9%
Provisional Zilver PTX
p = 0.06
log-rank
71.6%
Provisional BMS
At 5 years, Zilver PTX demonstrates a 47% reduction in reintervention compared to BMS

31. 5-year Primary Patency (PSVR < 2.0) Provisional Zilver PTX vs. BMS
72.4%
p = 0.03
log-rank
53.0%
Provisional BMS
At 5 years, Zilver PTX demonstrates a 41% reduction
in restenosis compared to BMS

32. Do it right the first time!
Zilver PTX has a proven drug effect in the SFA.
Cook Medical would like offer training to hospital staff to help get them onboard with drug elution in the periphery.