0. STENT Feature & Benefit

1. Learning Objectives Drawbacks of traditional POBA
Advantages of Stents in treatment of CAD
Manufacturing of Stents
Terminology: Deliverability and Deployment
Terminology: Implant Performance

2. Plain Old Balloon Angioplasty (POBA)
Goal: Get the artery open (first procedure in 1977)
BEFORE
DURING
When Balloon expands:
Plaque is compressed against vessel wall
Blood flow is restored
Vessel wall is stretched
How does this process work?
Balloon travels to target vessel on catheter:
Balloon is rapidly inflated at site of blockage
PLAQUE IN TARGET VESSEL: RESTRICTED BLOOD FLOW

3. Implications of POBA: Side Effectsx
Lumen
Lumen
Disease State
Plaque x
Post POBA
Elastic Recoil
Neointimal Formation
Observations Post POBA:
Pronounced Elastic Recoil and Neointimal Hyperplasia
Restenosis likely (40-60%)
Procedure results in minimal increase in lumen diameter

4. How Can Elastic Recoil be Reduced?
Stents: Hollow Metal Tubes
Implanted in target vessel to provide permanent support
Delivered to target vessel using catheter system – balloon expanded
Reduces recoil to ensure a larger lumen than with POBA

7. How Stents Work - Introduction
Stent positioned on balloon catheter
BEFORE DEPLOYMENT
AFTER DEPLOYMENT
Small Vessel
mm diameter
MAX: 3.0 mm diameter
BEFORE DEPLOYMENT
AFTER DEPLOYMENT
Large Vessel
mm diameter
MAX: 5.75 mm diameter

8. Bare Metal Stents: Reduced Recoil
EVIDENCE OF RESTENOSIS:
Lumen
Lumen
Lumen
Plaque
Disease State
Post
BMS
Minimal
Pronounced
Elastic Recoil
Neointimal Formation
Observations Post-BMS Deployment:
Reduced Elastic Recoil and Neointimal Hyperplasia
Restenosis pronounced (immune response leads to proliferation of ussmooth muscle cells)
Procedure results in minimal increase in lumen diameter

9. DES: Reduced Recoil and Restenosis
RESTENOSIS LIMITED
Lumen
Lumen
Lumen
Plaque
Disease State
Post
DES
Minimal
Pronounced
Elastic Recoil
Neointimal Formation
Observations Post-DES Deployment:
Reduced Elastic Recoil and Neointimal Hyperplasia
Restenosis reduced considerably
Procedure results in marked increase in lumen diameter

10. Deliverability and Deployment Characteristics of Implant
What Makes a Good Stent?
Deliverability and Deployment
Characteristics of Implant

11. Demonstration: What are You Holding?
You have an entire stent delivery system
Guide Wire
balloon expanded stent
balloon
catheter

12. Deliverability and Deployment
What Makes a Good Stent?
Deliverability and Deployment
1.) The ability to get the stent to the target vessel
2.) To safely and accurately deploy the stent
3.) Remove the delivery system from the patient
Implant Performance
1.) Physical characteristics of the device (construction)
2.) The ability of the device to “match” the target vessel.
3.) Measurement of long term safety and effectiveness (data)

13. Deliverability and Deployment – 1 of 3
CROSSABILITY: The degree to which a stent can be maneuvered past various lesions
Balloon and Stent
SYSTEM PROFILE
TIP PROFILE
PUSHABILITY: A measure of how accurately movement of the system outside the body translates to movement of the stent.
FLEXIBILITY: How readily a stent can be manipulated on while being delivered to a lesion. Structural stiffness can be a factor.
TRACKABILITY: How easily the catheter travels along the guide wire to the site of the lesion. Less friction is more desirable.

14. Deliverability and Deployment – 2 of 3
DELIVERABILITY: The general term physicians use to indicate the overall ease with which a stent system can be “delivered” to the lesion site.
Trackability: How easily the catheter travels along the guide wire to the site of the lesion. Less friction is more desirable.
Crossability: The degree to which a stent can be maneuvered past various lesions (profile of stent is critical.)
Determined by:
Flexibility: How readily a stent can be manipulated on while being delivered to a lesion. Structural stiffness can be a factor.
Pushability: A measure of how accurately movement of the system outside the body translates to movement of the stent.

15. Deliverability and Deployment – 3 of 3
MINIMAL BALLOON OVERHANG limits damage to tissue beyond target lesion.
RADIOPACITY: Stent should be visible under fluoroscopy
Markers will improve PLACEMENT ACCURACY on target lesion (critical)
Length before deployment
Difference is due to FORESHORTENING
Length after deployment

16. Implant Performance – 1 of 3
STENT DESIGN offers unique properties to suit varied target vessels.
METAL TYPE can impact strength, flexibility, radiopacity.
CONFORMABILITY is the ability of a stent to take the shape of the target vessel.
STRUT THICKNESS determines strength of stent, may also limit flexibility.

17. Implant Performance: 2 of 3
If the struts touch the vessel walls, the implant is said to have good STRUT APPOSITION
SCAFFOLDING offers uniform support of vessel wall:
Considerable Risks associated with Poor Strut Apposition, called MALAPPOSITION
closely related
METAL TO ARTERY RATIO determines coverage of target vessel: Can limit likelihood of PLAQUE PROLAPSE
RADIAL STRENGTH keeps the target vessel open, also called COMPRESSION RESISTANCE.

18. Implant Performance – 3 of 3
LONG TERM CLINICAL DATA is also an important measure of implant safety and efficacy. This is another important consideration during stent selection.
RESTENOSIS RATE
TLR (TARGET LESION REVASCULARIZATION)
MACE (MAJOR ADVERSE CARDIAC EVENT)
SUBACUTE STENT THROMBOSIS (SAT)
LATE LOSS (see next slide)

19. In-Stent Late Loss Limitations of Measurement
In-Segment
All of these vessels have the same in-stent late loss
In-stent Late Loss = .6 mm
Late loss is not sensitive to patterns of restenosis
In-stent Late Loss = .6 mm
One of the major limitations in assessing late lumen loss, is measurement itself. In this slide, while all vessels have a late loss of .6mm, patterns of restenosis are not identified.
Areas outside of the stent including the edges are not taken into consideration.
The edges are excluded from analysis
In-stent Late Loss = .6 mm

20. In-Segment Late Loss
In-segment late loss may allow a more complete evaluation of the treated segment because it looks at the margins
In-segment Late Loss provides a more detailed understanding of the entire lesion by including the analysis segment
In-segment
In-stent
5mm

21. In-stent Late loss levels below .6mm may not predict TLR
Late Loss Below a Certain Level May Not Be A Strong Predictor of TLR
In-stent Late loss levels below .6mm may not predict TLR
Source: Dr. Jeffrey Popma, MD Director of Interventional Cardiology, Brigham and Womens Hospital
Cypher is a trademark of Cordis Corporation

22. DES VS BMS

23. One Company’s Experience The Stent
Drug Eluting Stents – The New Paradigm
The
Carrier Matrix
The
Stent
Mechanical
integrity
Mechanical
Scaffolding
Carrier
Dose
Kinetic Release Rate (KDR)
Vascular Compatibility
The
Drug
(Chemical Entity)
The
Tissue
Tissue
Pharmacokinetics

24. One Company’s Experience The Stent
Mechanical scaffolding, mechanical integrity, vascular compatibility were considered when selecting the best stent design and material.
Current Technology
2nd & 3rd Generation
Early Technology
• Good scaffolding/
vessel support
• Increased flexibility
• Increased deliverability
• Good scaffolding/
vessel support
• Good flexibility
• Good deliverability
• Minimal scaffolding/
vessel support
• Minimally flexible
• Minimally deliverable
Result: Stainless Steel Stent = Vascular Compatibility &
good mechanical scaffolding/integrity

25. One Company’s Experience The Carrier Matrix - Polymer
Polymer: poly (styrene-b-isobutylene-b-styrene) (SIBS)
Why Polymer?
Dose Control
- uniform drug distribution
- ability to modify release rate
- consistent release
Protect the Drug
- no loss in handling or delivery
- consistent dose
Versatile
- one polymer can be used for a portfolio of drugs
- can be applied to various device geometries
- manufacturing processes are compatible w/ pharmaceuticals

26. One Company’s Experience The Carrier Matrix - Dose
Pre-clinical Dosing studies: The Approach
Evaluate Maximum Possible Dose
- Loading capacity of polymer/stent system
Identify the Maximum Tolerable Dose
- Understand “The Window” (safety margin)
Identify Minimum Effective Dose
FDA requirement: to demonstrate safety
of 3x overdose

27. One Company’s Experience The Carrier Matrix - Dose
Dosing Range – Preclinical Study
4 ug/mm2
2 ug/mm2
1ug/mm2
0.5 ug/mm2
345 ug
175 ug
85 ug
50 ug
Medial Thinning
Drug Effect
Thrombus
No Medial Thinning
Drug Effect
No Thrombus
Result: Determined the Safe & Potentially Therapeutic Range for the Artery

28. One Company’s Experience BSC - Brief History
BSC has cumulated more than a decade of experience in developing Drug-eluting stent technologies
Known proven chemical entity
Determined Dose & mechanism of action
Developed aggressive Vigilance program & complete product validation
Selected Drug platform
1995
1997
1999
2001
2003
2005
Conducted product
Clinical Trials
Searched & validated the Polymer Carrier
Determined & Validated
Dose Release Test Method (KDR)
Conducted
Post-Market Trials (28,000 +)

29. DES Efficacy
Roiron C. et al, Heart 2006;92:641–649

30. TAXUS® Stent 4-Year Meta-Analysis reinforces the positive benefit / risk profile
TAXUS I, II-SR, IV, V (N=2,797)
Risk
Benefit
p=0.17
p=0.24
p=0.78
p=0.87
p=0.83
p=0.86
p<0.0001
20.2
n=266
10.5
n=133
8.3
n=89
7.9
n=86
4-Yr Cumulative Events (%)
7.4
n=79
7.1
n=75
6.4
n=80
6.9
n=82
1.1
n=13
1.8
n=21
0.8
n=10
1.3
n=16
1.1
n=12
1.0
n=13
Primary ARC ST Def/Prob
Protocol ST
All Death
All MI
Q Wave MI
Death or Q Wave MI
TLR
Bare Metal Stent (N=1,397)
TAXUS® Stent (N=1,400)
*TAXUS Stent 4-year meta-analysis includes TAXUS I (5 yr), II-SR cohort I (4 yr), IV (4 yr), V (2 yr) (N=2,797).
Kaplan Meier estimate and p values from log rank

31. Clear Benefit of the TAXUS™ Stent Subset Data: Stent TLR Rates
TAXUS I, II-SR, IV, V Studies (N=2,797)
p<0.0001
p<0.0001
p<0.0001
p<0.0001
p<0.0001
31.3%
35.9%
27.7%
24.9%
TLR Rate (%)
20.2%
14.5%
13.4%
13.1%
12.8%
10.5%
N=2,797
n=715
n=965
n=341 ™
n=497
Adapted from Don Baim M.D. - FDA Panel Presentation December TAXUS™ Stent is not approved for use in patients with coronary artery reference vessel diameters < 2.25mm or in patients with lesions longer than 32mm. TAXUS Stent 4-year meta-analysis: See Glossary. Kaplan Meier estimate and p values from log rank

32. Q & A

33. Thank You

34. Hands on