Drug Eluting Stents:

1
Drug Eluting Stents

• Looking Forward
• Janine Lane
• Director Clinical Communication and Education
• Medtronic Vascular

2
Components of the Endeavor Stent
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
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
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Stent thrombosis Rates
According to Select Patient Characteristics
AntiplateletTherapyDiscontinuation
Diabetes
PriorBrachy
RenalFailure
Bifurcations
ULM
UA
Premature discontinuation From Milan/Sieburg
Experience ACC 05.
7
Late Stent thrombosis
After Anti-platelet Discontinuation
CYPHER TAXUS
335
343
375
442
Usually associated with minor surgical procedures
400
200
100
0
500
300
Day
McFadden EP et al. Lancet 2004 364151921
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At-Risk Patient Noncompliance
Adherence to Antiplatelet Medication
In at-risk patients from Western Europe over 24
months
78
62
Percent of Population
27
11
Bhatt DL et al. JAMA 2006 295(2)180-188
9
Safety Profile
No Late Stent Thrombosis in Over 1,300 Patients
Days Post Procedure
1
2
30
100
150
270
200
3
12
13
14
365
720
EI n100
1
EII n598
0.5
EII CA n296
0.0
EIII n323
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
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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

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Unmet Clinical Needs
12
Unmet Clinical NeedsExtended Drug Exposure


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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

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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

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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
9mo
30d
6mo
4 yr
3yr
2yr
12mo
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)
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Conclusion

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