Transcript Drug Eluting Stents

Drug Eluting Stents:
Looking Forward
Janine Lane
Director Clinical Communication and Education
Medtronic Vascular
Components of the Endeavor Stent
Cobalt Alloy
Modular stent
Strut thickness 0.0036’’
Delivery based
on discrete,
secure Technology
Zotarolimus
(Sirolimus analogue)
10 g/mm stent dosage
Biocompatible
PC Technology
(phosphorylcholinepolymer)
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
Unanswered Questions
•Impact of current drug eluting stents on longterm safety?
Stent Thrombosis
Myocardial Infarction
Death
•Ideal length of dual anti-platelet therapy?
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
Stent thrombosis Rates
According to Select Patient Characteristics
29.0%
8.7%
5.5%
*Antiplatelet
Therapy
Discontinuation
Prior
Brachy
Renal
Failure
*Premature discontinuation
From Milan/Sieburg Experience ACC 05.
3.5%
Bifurcations
3.2%
2.6%
ULM
Diabetes
1.3%
UA
Late Stent thrombosis
After Anti-platelet Discontinuation
CYPHER
335 343 375
442
TAXUS
Usually associated
with minor
surgical procedures
0
100
200
McFadden EP et al. Lancet 2004; 364:1519–21
Day
300
400
500
At-Risk Patient Noncompliance
Adherence to Antiplatelet Medication
In at-risk patients from Western Europe over 24
months:
Percent of Population
90
80
70
78%
60
62%
50
40
30
27%
20
10
11%
0
≥1 antiplatelet
agent
Bhatt DL et al. JAMA 2006; 295(2):180-188
Aspirin
Alone
Other agents
(i.e. PLAVIX)
Dual antiplatelet
therapy
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
Unmet Clinical Needs
Diabetics
Smaller Diameter
Vessels
Long Lesions
Left Main
Multi-Vessel
Disease
Clinically
unmet
needs in the
DES era
Diffuse Disease
Bifurcation
Lesions
AMI
Unmet Clinical Needs
(% Response)
Extended Drug Exposure
Smooth Muscle Cell
Migration/Proliferation
Thrombosis
3
Extracellular Matrix
Production
Extracellular Matrix
Reabsorption
Inflammation
Inflammation
14
Elution Duration
Drug In Tissue
90
440
1000
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
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
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
Endeavor CR Stent
100 Patients (includes 30 PK Sub-Study Patients)
12 Sites (New Zealand and Australia)
Clinical/MACE
30d
6mo
9mo
12mo
2yr
3yr
4 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)
5 yr
Conclusion
• Many more questions than answers
• Durability and safety
• Medtronic is assessing the theory of
delayed healing with the Endeavor CR
program