a d m i r a l

ADMIRAL

Abciximab beforeDirect Angioplasty and Stenting inMyocardialInfarctionRegardingAcute andLong term follow-up

ADMIRAL StudyADMIRAL StudyADMIRALADMIRAL

ADMIRALADMIRAL

1999, Oral Presentation

Aim of the StudyAim of the Study

To demonstrate the superiority of abciximab over placebo in primary PTCA with stenting in acute myocardial infarction

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Design-Inclusion CriteriaDesign-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

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Design-Exclusion CriteriaDesign-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

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Criteria for Stent ImplantationCriteria for Stent Implantation

• Coronary artery diameter > 2.5 mm

• Accessible by a stent

• No massive calcification

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Study DrugsStudy Drugs• Abciximab or Placebo

0.25 mg/kg bolus plus 0.125 g/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 usedESC

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DesignDesignAMI < 12 hoursrandomization

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

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Male (%) 85.2 78.7Age (years) 59.6 + 13.0 62.1 + 12.8Weight (kg) 75.9 + 12.5 76.5 + 15.1

Prior MI (%) 14.1 7.3*Prior UA (%) 8.7 7.3Prior Stable Angina (%) 4.7 4.7Prior PTCA (%) 6.7 2.7*Prior Stent (%) 0.1 0.1Prior CABG (%) 2.0 2.7CAD Family History (%) 28.9 28.7

Abciximabn = 150

DemographicsDemographicsPlacebon = 150

* p < 0.05ESC

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DemographicsDemographics

Smoker (%) 45.0 39.3Hypertension (%) 39.3 41.3Diabetes (%) 15.4 20.0Hyperlipidemia (%) 39.6 37.3Killip I (%) 89.9 89.3

Abciximabn = 150

Placebon = 150

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ProceduresProcedures

Initial coronary angiogram (%) 98.7 99.3Balloon angioplasty (%) 90.6 94.0Stent placed (%) 83.9 86.024-hour Coronary Angiogram (%) 84.6 87.3

Abciximabn = 150

Placebon = 150

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ProceduresProcedures

Stent placed (%) 83.9 86.0Saint-Come stent placed (%) 65.1 64.6

Number of stent(s) / patient (%)1 70.4 65.92 21.6 24.83 or more 8.0 9.3

Primary Success Rate (%) 94.4 94.6

Abciximabn = 150

Placebon = 150

ˆ

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MedicationsMedications

Aspirin (%) 96.6 96.0Ticlopidine (%) 83.2 84.7

Received Study Drug Agent (%)– Bolus 100.0 99.3– Bolus + Infusion 99.0 96.7

Prehospital administration (MICU) 10.7 11.3Emergency Room administration 14.1 15.3CCU or Cath Lab administration 75.2 73.4

Abciximabn = 150

Placebon = 150

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Time to TreatmentsTime 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

Abciximabn = 150

Placebon = 150

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AMI CharacteristicsAMI Characteristics

Anterior AMI (%) 35.8 40.7Inferior AMI (%) 50.7 46.7Other AMI (%) 14.5 12.6

Right Coronary Artery (%) 38.0 35.3Left Anterior Desc. Artery (%) 33.3 34.0Circumflex Coronary Artery (%) 9.3 10.0Other Coronary Arteries (%) 18.7 19.4Vein Graft (%) 0.7 1.3

Abciximabn = 150

Placebon = 150

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Primary EndpointPrimary 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

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Angiographic Results: TIMI 3 flow ratesAngiographic Results: TIMI 3 flow rates

10.3

83.7 84.489.9

82.5

21.0

90.4 92.0

0

20

40

60

80

100

Initial After Balloon After stent 24-hours

% o

f Pat

ient

s

Placebo Abciximab

p < 0.02

p < 0.01

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Left Ventricular FunctionLeft Ventricular Function

Abciximabn = 150

Placebon = 150

p < 0.05

51.4 54.6

0

25

50

75

24-h

our L

VEF

(%)

ESC

p < 0.05

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Primary Endpoint (30 days)Primary Endpoint (30 days)

7.3

15.3

0

5

10

15

20

% o

f Pat

ient

s

p = 0.02

- 52.3 %

Death, Recurrent MI, Urgent TVRDeath, Recurrent MI, Urgent TVR

Placebon = 150

Abciximabn = 150ESC

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Primary Endpoint Components (30 days)Primary Endpoint Components (30 days)

7.3

3.3

2.0

6.7

1.31.3

0

5

10

Death Recurrent MI Urgent TVR

% o

f Pat

ient

s

Placebo Abciximab

p = 0.33

- 54.8%

p = 0.65

- 35.0%

p = 0.02

- 80.0%

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

13.3

22.0

0

10

20

30

% o

f Pat

ient

s

p = 0.03

- 39.5 %

Placebon = 150

Abciximabn = 150ESC

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Bleeding EventsBleeding Events

1.3

6.7

2.6

4.0

0

2

4

6

8

10

Major Minor

% o

f Pat

ient

s

Placebo Abciximab

p = 0.50p = 0.02

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Major Bleeding EventsMajor Bleeding Events

2.6

0.91.7 2.02.0

4.0

0

2

4

6

8

10

Total CABG related Non-CABG related

% o

f Pat

ient

s

Placebo Abciximab

- Preliminary Results- Preliminary Results

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Major Bleeding EventsMajor Bleeding Events- Preliminary Results- Preliminary Results

0.61.3

0.70.6

1.42.0

0

2

4

6

Cerebral Blood Transfusions Other Major

% o

f Pat

ient

s

Placebo Abciximab

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ConclusionsConclusions

• 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 the24-hour arterial sheath

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a d m i r a l

Documents

oral presentationcriteria

oral presentationdesignami

oral presentationaim

prior stent

prior ptca

prior cabg

prior ua

prior mi