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Abciximab before
Direct Angioplasty and Stenting in
Myocardial
Infarction
Regarding
Acute and
Long term follow-up
ADMIRAL Study
ADMIRAL
Aim of the Study
To demonstrate the superiority of abciximab over placebo in primary PTCA with stenting in acute myocardial infarction
ESC
Design-Inclusion Criteria
Multicenter
Randomized
Double-Blind
Placebo Controlled
2 x 150 patients included-July 1997-Dec.1998
> 18 years old
Clinical Diagnosis of AMI ( ischemic pain > 30 min. )
Onset of symptoms < 12 hours
ST elevation > 1 mm in at least 2 contiguous leads
Referred for Urgent Primary PTCA
Written informed consent before randomization
ESC
Design-Exclusion Criteria
Major Exclusion Criteria
Hemorrhagic risk factors
Current episode previously treated by thrombolytics
Cardiogenic shock
Life expectancy < 1 year
Contraindications to PTCA
Stenosis < 50% and TIMI 3 Flow in the IRA
Occluded vessel of minor angiographic importance
Culprit lesion not visualized
ESC
Criteria for Stent Implantation
Coronary artery diameter > 2.5 mm
Accessible by a stent
No massive calcification
ESC
Study Drugs
Abciximab or Placebo 0.25 mg/kg bolus plus 0.125 mg/kg/min 12-hour infusion, as soon as AMI is diagnosed and before any sheath insertion, administered either in
the ambulance (MICU)
the emergency room
the catherization laboratory
Unfractionated heparin
Prior to intervention : 70 U/kg as a bolus (<7000 U)
Maintain ACT > 200 seconds pre and post PTCA until the second angiogram
Infusion rate of 7 U/kg/hour
Aspirin : 100-325 mg once daily during 6 months
Ticlopidine : 250 mg twice daily during 30 days if stent is used
ESC
Design
AMI < 12 hours
randomization
Abciximab
+
Heparin, ASA, Ticlopidine
Placebo
+
Heparin, ASA, Ticlopidine
First Coronary Angiography
PTCA + Stent
First Coronary Angiography
PTCA + Stent
Coronary Angiography
at 24 h and 6 Months
Coronary Angiography
at 24 h and 6 Months
Clinical evaluation
(24 h, 30 Days and 6 Months
ESC
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
Abciximab
n = 150
Demographics
Placebo
n = 150
* p < 0.05
ESC
Demographics
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
Abciximab
n = 150
Placebo
n = 150
ESC
Procedures
Initial coronary angiogram (%) 98.7 99.3
Balloon angioplasty (%) 90.6 94.0
Stent placed (%) 83.9 86.0
24-hour Coronary Angiogram (%) 84.6 87.3
Abciximab
n = 150
Placebo
n = 150
ESC
Procedures
Stent placed (%) 83.9 86.0
Saint-Come stent placed (%) 65.1 64.6
Number of stent(s) / patient (%)
1 70.4 65.9
2 21.6 24.8
3 or more 8.0 9.3
Primary Success Rate (%) 94.4 94.6
Abciximab
n = 150
Placebo
n = 150
?
ESC
Medications
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
Abciximab
n = 150
Placebo
n = 150
ESC
Time to Treatments
Time from onset of chest pain:
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
Abciximab
n = 150
Placebo
n = 150
ESC
AMI Characteristics
Anterior AMI (%) 35.8 40.7
Inferior AMI (%) 50.7 46.7
Other AMI (%) 14.5 12.6
Right Coronary Artery (%) 38.0 35.3
Left Anterior Desc. Artery (%) 33.3 34.0
Circumflex Coronary Artery (%) 9.3 10.0
Other Coronary Arteries (%) 18.7 19.4
Vein Graft (%) 0.7 1.3
Abciximab
n = 150
Placebo
n = 150
ESC
Primary Endpoint
Percentage of ischemic events within the first 30 days:
Death
Recurrent MI
Urgent target vessel revascularization (PTCA or CABG)
Urgent TVR: performed within 24 hours from the onset of a new acute ischemic episode
Recurrent MI
within 24 hours of study entry: CK or CK-MB definitions
between 24 h and 7 days: ECG or CK-MB definitions
> 7 days: ECG or CK-MB definitions
ESC
Angiographic Results: TIMI 3 flow rates
Left Ventricular Function
Primary Endpoint (30 days)
Primary Endpoint Components (30 days)
Secondary Endpoint (30 days)
Bleeding Events
Major Bleeding Events
2.6
0.9
1.7
2.0
2.0
4.0
0
2
4
6
8
10
Total
CABG related
Non-CABG related
% of Patients
Placebo
Abciximab
- Preliminary Results
ACC
Major Bleeding Events
- Preliminary Results
Conclusions
In patients with acute myocardial infarction, abciximab in conjunction with primary stenting positively improved:
early TIMI 3 flow rate
left ventricular function
30-day clinical results
The excess in minor bleeding may be due to the 24-hour arterial sheath
ESC