coordinated use of reopro and drug eluting stents · 6.9 1 nejm1994; 330:956 -61 2 1997; 336:1689...
TRANSCRIPT
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
Coordinated Use of ReoPro and Drug Eluting Stents
Abciximab 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 Stents
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
Coordinated Use of ReoPro and Drug Eluting Stents
ReoPro DES Stents
MI X
Death X
TVR X
Complementary Benefit
Coordinated Use of ReoPro and Drug Eluting Stents
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
Coordinated Use of ReoPro and Drug Eluting Stents
• 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 Stents
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
Coordinated Use of ReoPro and Drug Eluting Stents
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%
Coordinated 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
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
Coordinated 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 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?
Coordinated 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 Stents
No.
Complementary financially?
Coordinated Use of ReoPro and Drug Eluting Stents
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
Coordinated 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 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 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
Coordinated Use of ReoPro and Drug Eluting Stents
Conclusions
Coordinated 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.