ADMIRAL

Abciximab before Direct Angioplasty and Stenting in

Myocardial Infarction Regarding Acute and Long term
follow up

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 ADMIRAL: Objective
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.

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 ADMIRAL: Study Design
STEMI < 12 hours
Randomization
N=300

Abciximab Placebo
Initiated in the:
+ +
-Ambulance (MICU)
Heparin, ASA, Ticlopidine - Emergency Dept Heparin, ASA, Ticlopidine
- Cath Lab

First Coronary Angiography First Coronary Angiography

PTCA + Stent PTCA + Stent

Coronary Angiography Coronary Angiography

at 24 h and 6 Months at 24 h and 6 Months

Clinical evaluation
(24 h, 30 Days and 6 Months)
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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

Montalescot G, et al. N Engl J Med 2001;344:1895-903.

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 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.

Montalescot G, et al. N Engl J Med 2001;344:1895-903.

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 ADMIRAL: Drug Regimens
Regimen Study Drug Dose Heparin Dose ASA Dose Ticlopidine

Abciximab Bolus: 0.25 mg/kg Prior to intervention : 70 U/kg as a 100-325 mg No loading

bolus bolus (<7000 U) once daily dose
Infusion: 0.125 Maintain ACT > 200 s pre- and during 6 months
μg/kg/min (max. post-PTCA until the second 250 mg twice
10μg/min) for 12 angiogram daily during 30
hours days if stent is
Infusion rate of 7 U/kg/hour used
Placebo N/A Prior to intervention : 70 U/kg as a 100-325 mg No loading
bolus (<7000 U) once daily dose
Maintain ACT > 200 s pre- and during 6 months
post-PTCA until the second 250 mg twice
angiogram daily during 30
days if stent is
Infusion rate of 7 U/kg/hour used

Montalescot G, et al. N Engl J Med 2001;344:1895-903.

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 ADMIRAL: Patient Characteristics
Abciximab Placebo
(n=150) (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
* pHistory
CAD Family < 0.05 (%) 28.9 28.7
Montalescot G, et al. N Engl J Med 2001;344:1895-903.

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 ADMIRAL: Patient Characteristics
Abciximab Placebo
(n=150) (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

Montalescot G, et al. N Engl J Med 2001;344:1895-903.

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 ADMIRAL: Medications
Abciximab Placebo
(n=150) (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

Montalescot G, et al. N Engl J Med 2001;344:1895-903

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 ADMIRAL: Time to Treatment

Time from onset of chest pain: Abciximab Placebo

(n=150) (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

Montalescot G, et al. N Engl J Med 2001;344:1895-903.

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 ADMIRAL: Primary Endpoint (30 days)
Death, Recurrent MI, Urgent TVR
20
P= .01

14.6
15
% of Patients

10
6.0

0
Placebo Abciximab
(n = 150) (n = 150)
Montalescot G, et al. N Engl J Med 2001;344:1895-903.
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ADMIRAL: Primary Endpoint Components (30 days)

Montalescot G, et al. N Engl J Med 2001;344:1895-903.

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 ADMIRAL: Primary Endpoint (6 Months)
Death, Recurrent MI, Urgent TVR
20
P= .02
15.9

15
% of Patients

10 7.4

0
Placebo Abciximab
(n = 150) (n = 150)
Montalescot G, et al. N Engl J Med 2001;344:1895-903.
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ADMIRAL: Primary Endpoint Components (6 Months)

Montalescot G, et al. N Engl J Med 2001;344:1895-903.

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 ADMIRAL: Secondary Endpoint (30 days)
30 Death, Recurrent MI, Any Revascularization

P = 0.047
20.5
% of Patients

20

12.1

10

0
Placebo Abciximab
n = 150 n = 150
Montalescot G, et al. N Engl J Med 2001;344:1895-903. 15
 ADMIRAL: Angiographic Results:
TIMI 3 Flow Rates
Placebo (n=150) Abciximab (n=150)
P =.04 P =.33 P =.04
100 95.1 95.9 94.3
92.6
86.7
82.8

80
% of Patients

60

40
P =.01

20 16.8

5.4

0
Pre-Procedure Post-Procedure 24 Hours 6 Months
Montalescot G, et al. N Engl J Med 2001;344:1895-903.
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 ADMIRAL: Left Ventricular Function (24 hr)
75

57.0
53.9 P < .05
24-hour LVEF (%)

50

25

0
Placebo Abciximab
n = 150 n = 150

Montalescot G, et al. N Engl J Med 2001;344:1895-903

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 ADMIRAL: Safety
Bleeding
Placebo (n=150) Abciximab (n=150)

Montalescot G, et al. N Engl J Med 2001;344:1895-903.

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 ADMIRAL: Safety
Thrombocytopenia

P=.08
% Patients

Montalescot G, et al. N Engl J Med 2001;344:1895-903.

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