Kein Folientitel

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ClinicalTrials.gov Identifier NCT00133250
Abciximab in Patients with AMI Undergoing Primary
PCI After Clopidogrel Pretreatment
BRAVE-3 Trial Bavarian Reperfusion AlternatiVes
Evaluation-3 Trial
J. Mehilli, A. Kastrati, K. Huber, S. Schulz, J.
Pache, C.Markwardt, S. Kufner, F. Dotzer, K.
Schlotterbeck, J. Dirschinger, A. Schömig
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Financial Disclosure
No financial relationship to disclose
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Background

• Glycoprotein IIb/IIIa inhibitors (GPI) may
  improve the results of primary PCI in acute STEMI
  
• Pretreatment with a 300mg loading dose of
  clopidogrel improved the outcome of patients
  undergoing primary PCI in the setting of the
  CLARITY trial
• A higher, 600mg loading dose of clopidogrel
  further enhances and accelerates platelet
  inhibition

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Objective
..to assess whether abciximab further reduces the
infarct size in patients with acute ST-elevation
myocardial infarction undergoing primary PCI
after pre-treatment with 600 mg clopidogrel
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Inclusion Criteria

• Patients with acute ST-elevation myocardial
  infarction presenting within 24 hours from the
  onset of symptoms

• chest pain lasting more than 20 min
• 0.1 mV of ST-segment elevation in 2 limb leads
  or 0.2 mV in 2 contiguous precordial leads
  or new left bundle branch block on surface ECG

• Written, informed consent

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Exclusion Criteria

• Age gt 80 or lt 18 years
• Malignancies with a life expectancy lt1 year
• Cardiogenic shock or prolonged cardiopulmonary
  resuscitation
• Increased risk of bleeding
• Previous stroke within the last 3 months
• Active bleeding or bleeding diatheses
• Recent trauma or major surgery within the last
  30 days
• Suspected aortic dissection
• Recent use of GPI within 14 days
• Oral anticoagulation therapy with coumarin
  derivatives
• Severe uncontrolled hypertension (gt180mmHg,
  unresponsive to therapy)
• Relevant hematologic deviations
• (hemoglobin lt 100g/L or hct lt 34, platelet
  count lt 100 x 109/L)
• Coronary intervention within the last 30 days
• Known allergy to study medication, Pregnancy,
  Prior inclusion in the study

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Endpoints
Primary endpoint

• SPECT study (5-7 days after
• randomization)

• Final infarct size
• ( of the left ventricle)

Secondary endpoints

• Death
• Myocardial reinfarction
• Urgent revascularization
• Stroke
• Major and minor bleeding (TIMI criteria)
• Profound thrombocytopenia

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Sample Size Calculation

• Assumptions
• Infarct size of the LV in placebo group 16.9
  13.9
• Reduction of infarct size with abciximab by
  20
• ?-level 0.05 (two-sided) ?-error 0.10
• Sample size
• 353 patients per group with SPECT study
• to accommodate for possible missing SPECT
  studies
• 400 patients per group planned

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BRAVE-3 Study Sides Investigators

• Deutsches Herzzentrum, Munich, Germany
• PI M. Seyfarth
• Klinikum rechts der Isar, Munich, Germany
• PI J. Dirschinger
• Klinikum Traunstein, Traunstein, Germany
• PI K. Schlotterbeck
• Wilhelminenspital Vienna, Vienna, Austria
• PI K. Huber
• Klinikum Garmisch-Partenkirchen,
  Garmisch-Partenkirchen, Germany
• PI F. Dotzer

Study Chair A. Schömig Study Principal
Investigator A. Kastrati Data Co-ordinator
J. Mehilli
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Study Therapy (randomized, double-blind)
Clopidogrel 600 mg oral Aspirin 500 mg i.v. or
oral Unfractionated Heparin 5000 IU
Placebo n399 Additional UFH bolus of 70U/kg
Placebo infusion for 12h
Abciximab n401 Bolus 0.25 mg/kg Infusion 0.125
µg/kg/min/12h
Aspirin 200mg/day indefinitely Clopidogrel 2 x
75mg/day for 3 days Clopidogrel 75mg/day for at
least 4 weeks
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Baseline Characteristics
Age, yrs
Women,
Hypercholesterolemia,
Arterial hypertension,
Diabetes mellitus,
Current smoker,
Body mass index, kg/m2
Previous MI,
Previous CABG,
MeanSD
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Infarct Characteristics
Abciximab (n401)
Placebo (n399)
Infarct localization,
anterior
42
44
inferior
43
43
lateral
15
13
Killip Class,
I
76
77
II
18
18
III
4
3
IV
2
2
Arterial blood pressure, mmHg
systolic
13823
13922
diastolic
8014
7913
Heart rate, beats/min
7317
7316
MeanSD or
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Time Intervals
Symptom to admission
Admission to study drug
Clopidogrel loading to PCI
Admission to PCI
Median 25th, 75th percentiles in minutes
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Angiographic Characteristics
LV- ejection fraction,
Multivessel disease,
Infarct related coronary artery,
LAD
LCx
RCA
LMA
Bypass graft
MeanSD
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Infarct-Related Artery TIMI Flow Rates
After PCI
Prior to PCI
100
100


60
60
20
20
Abciximab
Placebo
Abciximab
Placebo
16
Collateral Distribution
IRA TIMI Flow rate lt2
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QCA Measurements
Vessel size, mm
MLD prior PCI, mm
DS prior PCI,
Balloon diameter, mm
Balloon-to-vessel ratio
Maximal balloon pressure, atm
MLD after PCI, mm
DS after PCI,
MeanSD
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Reperfusion Strategy
100
Drug-eluting stents

Bare metal stents
PTCA
60
Medical treatment
20
Abciximab
Placebo
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Primary Endpoint
Final infarct size Mean
Final infarct size Median 25th 75th percentile
40
P .76
P .47
LV
LV
30
20
10
10
9
0
Abciximab
Placebo
Abciximab
Placebo
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Primary Endpoint - Subgroup analysis -
Difference in Final Infarct Size ()
Age
Sex
Diabetes
Infarct localization
Interval pain onset to admission
Interval study drug to PCI
Interval clopidogrel to PCI
74.5 min
gt 74.5 min
-8
-6
-4
-2
0
2
4
6
8
Abciximab better
Placebo better
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30-Day Mortality
P .53
6

Abciximab
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Cumulative Incidence
Placebo
2
0
0
5
10
15
20
25
30
Days after randomization
22
Clinical Adverse Events- 30 days -
P .48
P .46
P .39

Abciximab
Placebo
23
Clinical Adverse Events- 30 days -
6
P .03
P .09
P .99

3.7
4
1.8
1.8
1.8
2
1.5
0
0
TIMI major
TIMI minor
lt20,000/µl
Thrombocytopenia
Bleeding
Abciximab
Placebo
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Conclusion
In patients with acute STEMI undergoing primary
PCI after pre-treatment with a 600mg loading dose
of clopidogrel, the additional use of abciximab
is not associated with further reduction in
infarct size