Richard MelsheimerDirector, Medical Affairs Europe

CentocorEli Lilly and Company

Coordinated Use of ReoPro and Drug Eluting Stents:Rationale and Evidence

• Mechanism and timing of action

• Clinical effect/benefit

• Indicated patients

• NICE guidelines

• Finances

• On-going trials

Coordinated - How?Coordinated Use of ReoPro and Drug Eluting StentsCoordinated Use of ReoPro and Drug Eluting Stents

Timing of Complications Associated with Percutaneous Coronary Interventions

Coordinated Use of ReoPro and Drug Eluting StentsCoordinated Use of ReoPro and Drug Eluting Stents

Restenosis Leading to TVRLate Myocardial Infarction

Abrupt ClosureSide Branch OcclusionsMyocardial InfarctionEarly MortalitySubacute Thrombosis

Late Mortality

0 – 7 days 30 days to 1 year and beyond

Abciximab vs StentsAbciximab vs StentsAbciximab vs StentsAbciximab vs Stents

What is ReoPro meant to do?

• Prevent thrombus formation

• Dissolve platelet-rich thrombus

• Improve procedural success

• Reduce peri-procedural MIs

• Cut the rate of ischemic events by 50%

• Reduce late mortality after PCI

VS

Coordinated Use of ReoPro and Drug Eluting StentsCoordinated Use of ReoPro and Drug Eluting Stents

Abciximab vs StentsAbciximab vs StentsAbciximab vs StentsAbciximab vs Stents

What are stents meant to do?

VS

• Secure a dissection

• Reduce restenosis by reducing elastic recoil

Coordinated Use of ReoPro and Drug Eluting StentsCoordinated Use of ReoPro and Drug Eluting Stents

Abciximab vs StentsAbciximab vs StentsAbciximab vs StentsAbciximab vs Stents

What are stents meant to do?

VS

• Secure a dissection

• Reduce restenosis by reducing elastic recoil

• Reduce restenosis by reducing SMC proliferation

Coordinated Use of ReoPro and Drug Eluting StentsCoordinated Use of ReoPro and Drug Eluting Stents

ReoPro DES Stents

MI X

Death X

TVR X

Complementary BenefitCoordinated Use of ReoPro and Drug Eluting StentsCoordinated Use of ReoPro and Drug Eluting Stents

In-Hospital Events Associated with DESIn-Hospital Events Associated with DESIn-Hospital Events Associated with DESIn-Hospital Events Associated with DES

Cypher Stent vs Bare StentCypher Stent vs Bare Stent

2.5

1.5

2.5 2.4

0

1

2

3

4

5

6

7

8

RAVEL SIRIUS

Bare StentCYPHER

% o

f P

atie

nts

p = NS p = 0.379

n = 1055n = 238

Coordinated Use of ReoPro and Drug Eluting StentsCoordinated Use of ReoPro and Drug Eluting Stents

http://www.tctmd.com/expert-presentations/table-2.html?product_id=3622&ppt_slide_id=54775&sort_key=13&large_image_p=1

• Physiological responses to trauma have not changed

– Inflammation – Distal embolization– LV function– Side branch occlusions– Microvascular flow– Thrombus formation

Other Complications and Considerations Coordinated Use of ReoPro and Drug Eluting StentsCoordinated Use of ReoPro and Drug Eluting Stents

Primary Endpoint-Primary Endpoint-Death, MI, Urgent Intervention (30 Days)Death, MI, Urgent Intervention (30 Days)

30

10.8

6.9

1NEJM 1994; 330:956-61 2NEJM 1997; 336:1689-96 3Lancet 1998; 352:87-92

0

16

12

8

4

00 30

Bolus

Bolus + Infusion

Placebo

p = 0.008

12.8

8.3

16

12

8

4

00

p < 0.001

Placebo + Stent

Abciximab + PTCA

5.3Abciximab + Stent

EPIC1 EPILOG2 EPISTENT3

16

12

8

4

030

p < 0.001

Placebo 11.7

5.2Abciximab*

Days

* low-dose heparin group

% of Patients with Events

Coordinated Use of ReoPro and Drug Eluting StentsCoordinated Use of ReoPro and Drug Eluting Stents

Clinical Outcomes - Target Lesion Revascularization

12.7 12.014.6

16.6

4.63.1 4.1

0.00

5

10

15

20

25

307 month* 6 month 6 month 9 month

RAVEL SIRIUSTAXUS SR TAXUS MR

p = ?? p =0.043 p = 0.006 p < 0.001

0% TLR in CYPHER arm through RAVEL 1 YEAR F/U

% o

f P

atie

nts 100% 75% 79% 62%

Coordinated Use of ReoPro and Drug Eluting StentsCoordinated Use of ReoPro and Drug Eluting Stents

Clinical Outcomes - Death

1.70.8

0.00.6

0.0 0.00.9

0.0

0

5

10

15 12 months 6 month 6 month 9 month

RAVEL SIRIUSTAXUS SR TAXUS MR

p = NS p =NS p = NS p = NS

% o

f P

atie

nts

1.7

Coordinated Use of ReoPro and Drug Eluting StentsCoordinated Use of ReoPro and Drug Eluting Stents

032599.1 Achenbach 15

3.1

2.0

JACC 2000; 35:922-28

p = 0.010

1 Year Survival in all Patients Following PCI 1 Year Survival in all Patients Following PCI With and Without AbciximabWith and Without Abciximab

EPIC, EPILOG, and EPISTENT - Meta-AnalysisEPIC, EPILOG, and EPISTENT - Meta-Analysis

Placebo

Abciximab

0 50 100 150 200 250 300 3500

1

2

3

4

Days of Randomization

Dea

th (

%)

n = 2,424

n = 4,110

 Death through 3 years by Tertile of Risk

Risk Tertile

% P

atie

nts

EPIC, EPILOG and EPISTENT CombinedEPIC, EPILOG and EPISTENT Combined

0% 1.5% 2.3%

Low Moderate High

• ReoPro– all patients undergoing PCI

• CYPHER Stent– patients with symptomatic ischemic disease, de novo

lesion < 30 mm with reference diameter between 2.25 mm and 5.00 mm

Indicated Patients?Coordinated Use of ReoPro and Drug Eluting StentsCoordinated Use of ReoPro and Drug Eluting Stents

• ReoPro - usage reflects new NICE guidelines– 50% of PCI - mainly high risk

• Cypher Stent– Predominantly high risk of restenosis– Diabetics– Long lesions– Diffuse disease– Restenotic lesions– Bifurcations– Left main

Actual Use in Patients?Coordinated Use of ReoPro and Drug Eluting StentsCoordinated Use of ReoPro and Drug Eluting Stents

No.

Complementary financially?Coordinated Use of ReoPro and Drug Eluting StentsCoordinated Use of ReoPro and Drug Eluting Stents

Enhanced Survival Benefit of Abciximab in DiabeticsEnhanced Survival Benefit of Abciximab in Diabetics

1 Year Mortality in Diabetics Following PCI 1 Year Mortality in Diabetics Following PCI with and without Abciximabwith and without AbciximabEPIC, EPILOG, and EPISTENT - Meta-AnalysisEPIC, EPILOG, and EPISTENT - Meta-Analysis

0 30 120 150 210 270 300 3600

1

2

3

4

Days of Randomization

Dea

th (

%)

5

6

60 90 180 240 330

2.0%p = 0.031

4.5

2.5

JACC 2000; 35:922-28

Placebo

Abciximab

n = 574

n = 888

1-year Mortality in Diabetics Who Underwent 1-year Mortality in Diabetics Who Underwent Multivessel InterventionMultivessel Intervention

% o

f P

atie

nts

Death 1-year

0

2

4

6

8

10

Placebo

Abciximab

Bhatt et al. JACC 2000;35:922-8

7.7

0.9

n = 65 n = 108

p = 0.018

88 %reduction

Ongoing or Upcoming Trials

Coordinated Use of ReoPro and Drug Eluting StentsCoordinated Use of ReoPro and Drug Eluting Stents

• ACE – carbo-stent vs carbo-stent+ReoPro in primary

PCI

• CARDIA

• CLEAREST

Trials

Coordinated Use of ReoPro and Drug Eluting StentsCoordinated Use of ReoPro and Drug Eluting Stents

CARDiaCARDia Study Design (n=600) Study Design (n=600)Abciximab Abciximab in Diabeticsin Diabetics

D, MI and Stroke

30 days, 6 month, 1, 2 and 5 year follow-up

Primary Endpoint: 1 Year

Diabetics eligible for CABG or PCIMultivessel disease

OR Complex Single Vessel w/Proximal LAD Stenosis or Complex Bifurc

vs

1:1 Randomization

CABGStent +

Abciximab +Clopidogrel

CLEARESTCLEAREST

Abciximab Abciximab in Diabeticsin Diabetics

Left main diseaseeligible for CABG or PCI

vs

1:1 Randomization

CABGDE Stent +

Abciximab +Clopidogrel

ReoPro DES Stents

MI X

Death X

TVR X

Complementary BenefitCoordinated Use of ReoPro and Drug Eluting StentsCoordinated Use of ReoPro and Drug Eluting Stents

ConclusionsCoordinated Use of ReoPro and Drug Eluting StentsCoordinated Use of ReoPro and Drug Eluting Stents

1. Reasons for using ReoPro in PCI have not changed.

2. Reasons for using (DE) stents have not changed.

3. These reasons are different.

4. Everything suggests these two therapies are complementary.

5. (As expected), drug-eluting stents have demonstrated dramatic reductions in TVR.

6. (As expected), ReoPro reduces early ischemic events and late mortality.