abciximab before direct angioplasty and stenting in
TRANSCRIPT
Abciximab before Direct Angioplasty and Stenting in Myocardial Infarction Regarding Acute and Long term
follow up
ADMIRAL
1
ADMIRAL: Objective
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To determine the effects of abciximab in the treatment of patients with STEMI being managed with primary PCI with stenting.
Montalescot G, et al. N Engl J Med 2001;344:1895-903.
Initiated in the: -Ambulance (MICU) - Emergency Dept - Cath Lab
ADMIRAL: Study Design
3
STEMI < 12 hoursRandomization
N=300
Abciximab+
Heparin, ASA, Ticlopidine
Placebo+
Heparin, ASA, Ticlopidine
First Coronary AngiographyPTCA + Stent
First Coronary AngiographyPTCA + Stent
Coronary Angiographyat 24 h and 6 Months
Coronary Angiographyat 24 h and 6 Months
Clinical evaluation(24 h, 30 Days and 6 Months)
Montalescot G, et al. N Engl J Med 2001;344:1895-903.
ADMIRAL: Inclusion Criteria
• Clinical diagnosis of STEMI ( ischemic pain > 30 min. )• Onset of symptoms < 12 h• ST elevation > 1 mm in at least 2 contiguous leads• Referred for urgent primary PCI
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Montalescot G, et al. N Engl J Med 2001;344:1895-903.
ADMIRAL: Endpoints• Primary:
– Composite of death, reinfarction, or urgent revascularization of the target vessel at 30 days after randomization
• Secondary:– Composite of death, reinfarction, or any revascularization (percutaneous
coronary revascularization or CABG on an urgent or elective basis) at 30 days and at 6 months.
– Death or reinfarction at 30 days and at 6 months
– Death, reinfarction, or urgent revascularization of the target vessel at 6 months
– TIMI flow grade before, immediately after, 24 hours after, and 6 months after the revascularization procedure
– Left ventricular ejection fraction within 24 hours and at 6 months after the revascularization procedure.
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Montalescot G, et al. N Engl J Med 2001;344:1895-903.
ADMIRAL: Drug Regimens
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Regimen Study Drug Dose Heparin Dose ASA Dose Ticlopidine
Abciximab Bolus: 0.25 mg/kg bolus Infusion: 0.125 μg/kg/min (max. 10μg/min) for 12 hours
Prior to intervention : 70 U/kg as a bolus (<7000 U)Maintain ACT > 200 s pre- and post-PTCA until the second angiogram
Infusion rate of 7 U/kg/hour
100-325 mg once daily during 6 months
No loading dose
250 mg twice daily during 30 days if stent is used
Placebo N/A Prior to intervention : 70 U/kg as a bolus (<7000 U)Maintain ACT > 200 s pre- and post-PTCA until the second angiogram
Infusion rate of 7 U/kg/hour
100-325 mg once daily during 6 months
No loading dose
250 mg twice daily during 30 days if stent is used
Montalescot G, et al. N Engl J Med 2001;344:1895-903.
ADMIRAL: Patient Characteristics
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* p < 0.05
Montalescot G, et al. N Engl J Med 2001;344:1895-903.
Abciximab(n=150)
Placebo(n=150)
Male (%) 85.2 78.7
Age (years) 59.6 + 13.0 62.1 + 12.8
Weight (kg) 75.9 + 12.5 76.5 + 15.1
Prior MI (%) 14.1 7.3*
Prior UA (%) 8.7 7.3
Prior Stable Angina (%) 4.7 4.7
Prior PTCA (%) 6.7 2.7*
Prior Stent (%) 0.1 0.1
Prior CABG (%) 2.0 2.7
CAD Family History (%) 28.9 28.7
ADMIRAL: Patient Characteristics
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Montalescot G, et al. N Engl J Med 2001;344:1895-903.
Abciximab(n=150)
Placebo(n=150)
Smoker (%) 45.0 39.3
Hypertension (%) 39.3 41.3
Diabetes (%) 15.4 20.0
Hyperlipidemia (%) 39.6 37.3
Killip I (%) 89.9 89.3
ADMIRAL: Medications
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Montalescot G, et al. N Engl J Med 2001;344:1895-903
Abciximab(n=150)
Placebo(n=150)
Aspirin (%) 96.6 96.0
Ticlopidine (%) 83.2 84.7
Received Study Drug Agent (%)
– Bolus 100.0 99.3
– Bolus + Infusion 99.0 96.7
Prehospital administration (MICU) 10.7 11.3
Emergency Room administration 14.1 15.3
CCU or Cath Lab administration 75.2 73.4
ADMIRAL: Time to Treatment
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Montalescot G, et al. N Engl J Med 2001;344:1895-903.
Time from onset of chest pain: Abciximab(n=150)
Placebo(n=150)
- to treatment (hrs) 3.2 + 2.5 3.5 + 2.4
- to bolus (hrs) 3.7 + 2.1 4.1 + 2.5
- to coronary angiogram (hrs) 3.9 + 2.1 4.4 + 2.6
- to PTCA (hrs) 4.1 + 2.1 4.6 + 2.6
ADMIRAL: Primary Endpoint (30 days)
6.0
14.6
0
5
10
15
20
% o
f P
atie
nts
P= .01
Death, Recurrent MI, Urgent TVR
Placebo(n = 150)
Abciximab(n = 150)
Montalescot G, et al. N Engl J Med 2001;344:1895-903.11
ADMIRAL: Primary Endpoint Components (30 days)
Montalescot G, et al. N Engl J Med 2001;344:1895-903.
12
ADMIRAL: Primary Endpoint (6 Months)
7.4
15.9
0
5
10
15
20
% o
f P
atie
nts
P= .02
Death, Recurrent MI, Urgent TVR
Placebo(n = 150)
Abciximab(n = 150)
Montalescot G, et al. N Engl J Med 2001;344:1895-903.13
ADMIRAL: Primary Endpoint Components (6 Months)
Montalescot G, et al. N Engl J Med 2001;344:1895-903.
14
ADMIRAL: Secondary Endpoint (30 days)
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Death, Recurrent MI, Any Revascularization
12.1
20.5
0
10
20
30
% o
f P
atie
nts
P = 0.047
Placebon = 150
Abciximabn = 150
Montalescot G, et al. N Engl J Med 2001;344:1895-903.
ADMIRAL: Angiographic Results: TIMI 3 Flow Rates
16.8
92.695.1
86.7 82.8
5.4
95.9 94.3
0
20
40
60
80
100
Pre-Procedure Post-Procedure 24 Hours
% o
f P
atie
nts
Placebo (n=150) Abciximab (n=150)P =.04
P =.01
Montalescot G, et al. N Engl J Med 2001;344:1895-903. 16
6 Months
P =.04P =.33
ADMIRAL: Left Ventricular Function (24 hr)
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Abciximabn = 150
Placebon = 150
53.957.0
0
25
50
75
24-h
ou
r L
VE
F (
%)
P < .05
Montalescot G, et al. N Engl J Med 2001;344:1895-903
ADMIRAL: Safety
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Montalescot G, et al. N Engl J Med 2001;344:1895-903.
BleedingPlacebo (n=150) Abciximab (n=150)
ADMIRAL: Safety
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P=.08
% P
atie
nts
% P
atie
nts
Thrombocytopenia
Montalescot G, et al. N Engl J Med 2001;344:1895-903.