1. Drug Eluting Stents: Looking Forward Janine Lane
Director Clinical Communication and Education
Medtronic Vascular

2. Components of the Endeavor Stent
Cobalt Alloy
Modular stent
Strut thickness ’’
Biocompatible PC Technology
(phosphorylcholinepolymer)
Delivery based on discrete,
secure Technology
Zotarolimus
(Sirolimus analogue)
10 g/mm stent dosage

3. Lessons Learned
Antiproliferative drugs consistently reduce need for repeat intervention
Current drug eluting stents are associated with varied angiographic results
Perception of the cost benefit of drug eluting stents is not uniform

4. Unanswered Questions
Impact of current drug eluting stents on long-term safety?
Stent Thrombosis
Myocardial Infarction
Death
Ideal length of dual anti-platelet therapy?

5. = increased necessity for prolonged dual antiplatelet regimens
Stent Thrombosis
Factors to Consider
The polymer
Inflammatory
Thrombogenic
The drug
Delayed Endothelization
Late incomplete apposition
The patient
(more complex lesions = more thrombogenic milieu)
= increased necessity for prolonged dual antiplatelet regimens
Late Stent Thrombosis (“LST”) is a well known, potentially life threatening complication of PCI/Stenting.
There are four widely suspected underlying causes of LST: discontinuation of anti-platelet therapy, late incomplete apposition, polymer hypersensitivity/inflammation and delayed endothelialization.
As you will see in the following slides, Endeavor effectively reduces the risk of each of these causes of LST
This is reflected in the excellent Endeavor clinical program results with 0% LST after 10 days in more than 1200 pts.

6. *Antiplatelet Therapy Discontinuation
Stent thrombosis Rates
According to Select Patient Characteristics
*Antiplatelet Therapy Discontinuation
Prior Brachy
Renal Failure
Bifurcations
ULM
Diabetes UA
The incidence of stent thrombosis according to selected patient characteristics was 29% in pts with premature antiplatelet therapy discontinuation, 8.7% in prior brachytherapy at the target vessel, 5.5% with renal failure, 3.5% in bifurcations, 3.2% in unprotected left main treated, 2.6% in diabetes, and 1.3% in unstable angina
*Premature discontinuation
From Milan/Sieburg Experience ACC 05.

7. Usually associated with minor
Late Stent thrombosis
After Anti-platelet Discontinuation
CYPHER
TAXUS
335
343
375
442
Usually associated with minor
surgical procedures
100
200
300
400
500
Day
McFadden EP et al. Lancet 2004; 364:1519–21

8. At-Risk Patient Noncompliance
Adherence to Antiplatelet Medication
In at-risk patients from Western Europe over 24 months:
Dual antiplatelet therapy
Other agents (i.e. PLAVIX)
Aspirin
Alone
≥1 antiplatelet agent
78%
62%
Percent of Population
27%
11%
Bhatt DL et al. JAMA 2006; 295(2):

9. Safety Profile: No Late Stent Thrombosis in Over 1,300 Patients EI EII
Days Post Procedure 1 2 3 12 13 14 30
100
150
270
200
365
720 EI
n=100
= 1%
EII
n=598
= 0.5%
EII CA
n=296
= 0.0%
EIII
n=323
= 0.0%
Defined as angiographic thrombus or subacute closure within the stented vessel at the time of the clinically driven angiographic restudy for documented ischemia (chest pain and ECG changes). Any death not attributed to a non-cardiac cause within the first 30 days is considered a surrogate for stent thrombosis in the absence of documented angiographic stent patency.
Overall Thrombosis = 0.3%

10. Unanswered Questions Long term benefits (health care economics)
Stent design itself:
Elution characteristics
Ideal drug or drugs
Ideal delivery mechanism
Patient responses:
healing times of complex disease states
why current drug eluting stents sometimes fail
Can we improve safety while maintaining aggressive neointimal suppression

11. Unmet Clinical Needs Clinically unmet needs in the DES era
Diffuse Disease
Long Lesions
Smaller Diameter
Vessels
Bifurcation
Lesions
Left Main
AMI
Diabetics
Multi-Vessel
Disease

12. Migration/Proliferation
Unmet Clinical Needs Extended Drug Exposure
(% Response)
Extracellular Matrix
Production
Smooth Muscle Cell
Migration/Proliferation
Inflammation
Reabsorption 90
Thrombosis 3 14
440
1000
Elution Duration
Drug In Tissue

13. Potential Solutions One new drug eluting stent:
Multiple/combination drugs
Different delivery mechanism
Choice of drug eluting stents from one supplier
Indication specific drug eluting stents
One drug eluting stent with different versions

14. Next Generation DES Pipeline
Endeavor Controlled Response (CR)
Novel, Medtronic designed polymer coating
Tunable elution kinetics to match the breadth of healing needs in complex lesions
Capability to deliver multiple drugs

15. Medtronic RESOLUTE Clinical Trial
Single De Novo Native Coronary Artery Lesions
Stent Diameters: 2.5, 3.0, 3.5mm
Stent Lengths: 18, 24, 30mm (8/9mm bailout)
Lesion Length: 14-27mm
Drug Dose: 1.6 g/mm2 stent surface area
Pre-dilatation required
100 Patients (includes 30 PK Sub-Study Patients)
12 Sites (New Zealand and Australia)
Endeavor CR Stent
Clinical/MACE
30d
6mo
9mo
12mo
2yr
3yr
4 yr
5 yr
Angio/IVUS (all patients)
Primary Endpoint: Late lumen loss (in-stent) at 9 mo
Secondary Endpoints:
1. MACE rate at 30 day and 6, 9, 12 mo
2. Acute success (device, lesion, procedure)
3. Angiographic parameters at 9 mo (%DS, LL, LL index, ABR, MLD)
4. TVF at 9 mo
5. Clinically driven TLR at 9 mo
6. Neointimal hyperplastic volume and percent volume obstruction (%VO) at 9 mo
7. PK Sub-Study Pharmacokinetic parameters (Cmax, Tmax, AUC, CL corresponding to AUC)

16. Conclusion Many more questions than answers Durability and safety
Medtronic is assessing the theory of delayed healing with the Endeavor CR program