Coordinated Use of ReoPro and Drug Eluting Stents · 6.9 1 NEJM1994; 330:956 -61 2 1997; 336:1689 96 3Lancet 1998; 352:87 92 0 16 12 8 4 0 0 30 Bolus Bolus + Infusion Placebo p =

Richard Melsheimer

Director, Medical Affairs Europe

Centocor

Eli 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 Stents

Timing of Complications Associated with Percutaneous Coronary Interventions

Coordinated 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 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


Abciximab vs Stents

What are stents meant to do?

VS

• Secure a dissection

• Reduce restenosis by reducing elastic

recoil


Abciximab vs Stents

What are stents meant to do?

VS

• Secure a dissection

• Reduce restenosis by reducing elastic

recoil

• Reduce restenosis by reducing SMC

proliferation


ReoPro DES Stents

MI X

Death X

TVR X

Complementary Benefit


In-Hospital Events Associated with DES

Cypher Stent vs Bare Stent

2.5

1.5

2.5 2.4

0

1

2

3

4

5

6

7

8

RAVEL SIRIUS

Bare Stent

CYPHER

% o

f P

ati

en

ts

p = NS p = 0.379

n = 1055n = 238


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

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


Primary Endpoint-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


Clinical Outcomes -Target Lesion Revascularization

12.7 12.0

14.616.6

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

ati

en

ts

100% 75% 79% 62%


Clinical Outcomes - Death

1.70.8

0.00.6

0.0 0.00.9

0.0

0

5

10

1512 months 6 month 6 month 9 month

RAVEL SIRIUSTAXUS SR TAXUS MR

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

% o

f P

ati

en

ts

1.7


032599.1 Achenbach 15

3.1

2.0

JACC 2000; 35:922-28

p = 0.010

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

EPIC, EPILOG, and EPISTENT - Meta-Analysis

Placebo

Abciximab

0 50 100 150 200 250 300 350

0

1

2

3

4

Days of Randomization

Death

(%

)

n = 2,424

n = 4,110

Death through 3 years by Tertile of Risk

1.4

5.8

11.6

1.4

4.3

9.3

0

2

4

6

8

10

12

14

Placebo

Abciximab

Risk Tertile

%

Pati

en

ts

EPIC, EPILOG and EPISTENT Combined

D 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?


• 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?


No.

Complementary financially?


Enhanced Survival Benefit of Abciximab in Diabetics

1 Year Mortality in Diabetics Following PCI with and without Abciximab

EPIC, EPILOG, and EPISTENT - Meta-Analysis

0 30 120 150 210 270 300 360

0

1

2

3

4

Days of Randomization

Death

(%

)

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 Multivessel Intervention

% o

f P

ati

en

ts

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


• ACE

– carbo-stent vs carbo-stent+ReoPro in primary PCI

• CARDIA

• CLEAREST

Trials


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 PCI

Multivessel 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 disease

eligible for CABG or PCI

vs

1:1 Randomization

CABGDE Stent +

Abciximab +Clopidogrel

ReoPro DES Stents

MI X

Death X

TVR X

Complementary Benefit


Conclusions


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.

Documents

Coordinated Use of ReoPro and Drug Eluting Stents · 6.9 1 NEJM1994; 330:956 -61 2 1997; 336:1689 96 3Lancet 1998; 352:87 92 0 16 12 8 4 0 0 30 Bolus Bolus + Infusion Placebo p =