Value of Abciximab in Patients With AMI Undergoing PCI After High Loading Dose of Clopidogrel Pretreatment - BRAVE-3


The goal of this trial was to assess if there was an incremental benefit from the use of abciximab, a glycoprotein (GP) IIb/IIIa inhibitor, in patients with ST-elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI), after pretreatment with 600 mg of clopidogrel.


Abciximab would be associated with a significant reduction in left ventricular (LV) infarct size in patients with STEMI undergoing PCI compared with placebo, after pretreatment with 600 mg of clopidogrel.

Study Design

Study Design:

Patients Enrolled: 800
Mean Follow Up: 5-7 days
Mean Patient Age: 62.1 years
Female: 26
Mean Ejection Fraction: 47.9%

Patient Populations:

  • Patients with STEMI presenting within 24 hours of symptom onset, and who were undergoing PCI
  • Received 600 mg of clopidogrel prior to the procedure


  • Age <18 or >80 years
  • Malignancy with life expectancy <1 year
  • Cardiogenic shock or prolonged cardiopulmonary resuscitation
  • Increased risk of bleeding, including recent stroke, active bleeding, or bleeding diathesis; recent trauma or surgery; suspected aortic dissection; recent use of GP IIb/IIIa inhibitors, oral anticoagulation with warfarin, or uncontrolled systolic hypertension >180 mm Hg
  • Anemia (hemoglobin <10 g/dl) or thrombocytopenia
  • PCI within 30 days
  • Known allergy to study medication
  • Pregnancy
  • Thrombolytics for the index MI

Primary Endpoints:

  • LV infarct size, calculated as the final perfusion defect on a SPECT study performed 5-7 days after enrollment

Secondary Endpoints:

  • Death
  • MI
  • Urgent revascularization
  • Stroke
  • Major and minor bleeding

Drug/Procedures Used:

Patients undergoing PCI, after pretreatment with 500 mg of aspirin, 600 mg of clopidogrel, and 60 U/kg (maximum dose: 5000 U) of unfractionated heparin (UFH), were randomly assigned to either abciximab (bolus of 0.25 mg/kg followed by an infusion of 0.125 µg/kg/min for 12 hours) or placebo (additional UFH of 70 U/kg, followed by placebo infusion for 12 hours).

Concomitant Medications:

All patients received a daily dose of 200 mg of aspirin indefinitely. Clopidogrel was given as 150 mg daily for 3 days, followed by 75 mg daily for at least 1 month.

Principal Findings:

A total of 800 patients were randomized, 401 to the abciximab arm and 399 to the placebo arm. About 17.5% of patients had diabetes, and 63% had evidence of multivessel disease on angiography. About 43% of the infarcts were anterior in location, and the majority (76.5%) were Killip class I. The median times from symptom onset to admission were 210 minutes and 216 minutes in the abciximab and control arms, respectively, whereas the median door-to-balloon times were 78 minutes and 80 minutes, respectively (p>0.05 for both).

Thrombolysis In Myocardial Infarction (TIMI) 3 flow was established in 92% of patients in both arms. Drug-eluting stents were deployed in about 44% of the patients in both arms, whereas bare-metal stents were deployed in about 49% of the patients. The mean final infarct size was 15.7% vs. 16.6% in the abciximab and control groups, respectively (p = 0.47).

Mortality at 30 days was 3.2% versus 2.5%, respectively (p = 0.53). Similarly, the incidence of definite stent thrombosis was similar between the two arms (0.3% vs. 0.8%, p = 0.31). The composite endpoint of death, MI, stroke, or urgent revascularization was 5.0% versus 3.8%, respectively (p = 0.40). The incidence of minor bleeding was nonsignificantly elevated in the abciximab arm compared with the control arm (3.7% vs. 1.8%, p = 0.09), whereas the incidence of thrombocytopenia was significantly higher (1.5% vs. 0%, p = 0.03). Major bleeding complications were similar between the two arms (1.8% vs. 1.8%).


Earlier GP IIb/IIIa inhibitor studies such as the Intracoronary Stenting and Antithrombotic Regimen-2 (ISAR-2) and Abciximab-Carbostent Evaluation (ACE) trials had demonstrated a reduction in composite outcomes at 30 days in patients with acute MI undergoing PCI with stenting who were treated with GP IIb/IIIa inhibitors compared with placebo. However, these studies were done without routine pretreatment with clopidogrel.

The BRAVE-3 trial, therefore, sought to identify the ideal antiplatelet strategy in patients with STEMI. The results of this large randomized clinical trial indicate that in patients with STEMI undergoing PCI following pretreatment with 600 mg of clopidogrel, the additional use of abciximab is not associated with a further reduction in infarct size or mortality, but is associated with a significantly increased risk of thrombocytopenia and a trend toward increased TIMI minor bleeding.

One potential limitation of this trial is that patients were enrolled up to 24 hours after symptom onset, which may have limited their ability to significantly salvage myocardium at risk. It is also possible that the low rate of periprocedural MIs in this trial precluded the demonstration of a small benefit with abciximab, as was noted by these investigators in the ISAR-REACT 2 trial, which enrolled patients with non-ST elevation acute coronary syndromes.


Mehilli J, Kastrati A, Schulz S, et al., on behalf of the Bavarian Reperfusion Alternatives Evaluation-3 (BRAVE-3) Study Investigators. Abciximab in Patients With Acute ST-Segment-Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention After Clopidogrel Loading. A Randomized Double-Blind Trial. Circulation 2009;Mar 30:[Epub ahead of print].

Pretreatment With a High Loading Dose of Clopidogrel and Value of Abciximab During Primary Coronary Intervention in Patients With Acute Myocardial Infarction: Results of the Randomized BRAVE-3 Trial. Presented by Dr. Julinda Mehilli at the SCAI-ACC i2 Summit/American College of Cardiology Annual Scientific Session, Chicago, IL, March/April 2008.

Clinical Topics: Acute Coronary Syndromes, Anticoagulation Management, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, ACS and Cardiac Biomarkers, Anticoagulation Management and ACS, Heart Failure and Cardiac Biomarkers, Interventions and ACS

Keywords: Myocardial Infarction, Acute Coronary Syndrome, Stroke, Platelet Aggregation Inhibitors, Drug-Eluting Stents, Heparin, Coronary Disease, Ticlopidine, Immunoglobulin Fab Fragments, Platelet Membrane Glycoprotein IIb, Percutaneous Coronary Intervention, Thrombosis, Diabetes Mellitus, Thrombocytopenia, Platelet Glycoprotein GPIIb-IIIa Complex

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