Drug Eluting Stents:Drug Eluting Stents:

Looking ForwardLooking Forward

Janine LaneJanine LaneDirector Clinical Communication and EducationDirector Clinical Communication and EducationMedtronic VascularMedtronic Vascular

Components of the Endeavor StentComponents of the Endeavor Stent

Cobalt AlloyModular stentStrut thickness 0.0036’’

BiocompatiblePC Technology (phosphorylcholinepolymer)

Delivery basedon discrete,secure Technology

Zotarolimus(Sirolimus analogue)10 g/mm stent dosage

Lessons LearnedLessons 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 QuestionsUnanswered Questions

•Impact of current drug eluting stents on long-term safety?

Stent ThrombosisMyocardial InfarctionDeath

•Ideal length of dual anti-platelet therapy?

Stent ThrombosisStent Thrombosis

•The The polymer polymer – InflammatoryInflammatory – ThrombogenicThrombogenic

The drug The drug – Delayed EndothelizationDelayed Endothelization– Late incomplete appositionLate incomplete apposition

The patient The patient – (more complex lesions =(more complex lesions =more thrombogenic milieu)more thrombogenic milieu)

= increased necessity for prolonged dual antiplatelet regimens

Factors to ConsiderFactors to Consider

29.0%

8.7%5.5%

3.5% 3.2% 2.6%1.3%

*Antiplatelet*AntiplateletTherapyTherapy

DiscontinuationDiscontinuation

DiabetesDiabetesPriorPriorBrachyBrachy

RenalRenalFailureFailure

BifurcationsBifurcations ULMULM UAUA

*Premature discontinuationFrom Milan/Sieburg Experience ACC 05.

Stent thrombosis RatesStent thrombosis RatesAccording to Select Patient CharacteristicsAccording to Select Patient Characteristics

Day4002001000 500300

CYPHER

TAXUS

335 343 375 442

McFadden EP et al. Lancet 2004; 364:1519–21

Usually associated with minor

surgical procedures

Late Stent thrombosis Late Stent thrombosis After Anti-platelet DiscontinuationAfter Anti-platelet Discontinuation

0

10

20

30

40

50

60

70

80

90

Dual antiplatelet therapy

Other agents (i.e. PLAVIX)

AspirinAlone

≥1 antiplatelet agent

11%

27%

78%

62%

Pe

rce

nt

of

Po

pu

lati

on

At-Risk Patient NoncomplianceAt-Risk Patient Noncompliance

In at-risk patients from Western Europe over 24 months:

Adherence to Antiplatelet MedicationAdherence to Antiplatelet Medication

Bhatt DL et al. JAMA 2006; 295(2):180-188

Unanswered QuestionsUnanswered Questions

•Long term benefits (health care economics)•Stent design itself:

Elution characteristicsIdeal drug or drugsIdeal delivery mechanism

•Patient responses:healing times of complex disease stateswhy current drug eluting stents

sometimes fail•Can we improve safety while maintaining aggressive neointimal suppression

Clinically unmet

needs in the DES era

Clinically unmet

needs in the DES era

Diffuse DiseaseDiffuse Disease

Long LesionsLong Lesions

Smaller DiameterVessels

Smaller DiameterVessels

BifurcationLesions

BifurcationLesions

Left MainLeft Main AMIAMI

DiabeticsDiabeticsMulti-Vessel

DiseaseMulti-Vessel

Disease

Unmet Clinical NeedsUnmet Clinical Needs

Drug In TissueDrug In Tissue

Elution DurationElution Duration

Unmet Clinical NeedsUnmet Clinical NeedsExtended Drug Exposure Extended Drug Exposure

(%

(% R

espo

nse)

Res

pons

e) Extracellular Matrix

Production

Smooth Muscle Cell

Migration/Proliferation

Inflammation

Extracellular Matrix

Reabsorption

9090

Thrombosis

33 1414 440440 10001000

Inflammation

Potential SolutionsPotential 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

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

Next Generation DES PipelineNext Generation DES Pipeline

Medtronic RESOLUTE Clinical TrialMedtronic RESOLUTE Clinical Trial

Single De Novo Native Coronary Artery LesionsStent 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 areaPre-dilatation required

100 Patients (includes 30 PK Sub-Study Patients)12 Sites (New Zealand and Australia)

Endeavor CR Stent

Clinical/MACE

Angio/IVUS (all patients)30d 6mo 4 yr3yr2yr9mo9mo 12mo 5 yr

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)

ConclusionConclusion

• Many more questions than answersMany more questions than answers• Durability and safetyDurability and safety• Medtronic is assessing the theory of Medtronic is assessing the theory of

delayed healing with the Endeavor CR delayed healing with the Endeavor CR programprogram