Beyond 12 Hours Reperfusion Alternative Evaluation Trial - BRAVE-2


The goal of the trial was to evaluate treatment with percutaneous coronary intervention (PCI) among patients with ST elevation myocardial infarction (MI) presenting longer than 12 hours after symptom onset without persistent chest pain.

Study Design

Study Design:

Patients Screened: 2453
Patients Enrolled: 365
Mean Follow Up: 30 days
Mean Patient Age: Median age 66 years
Female: 26
Mean Ejection Fraction: 50% in the invasive group

Patient Populations:

Presenting with acute MI from 12-48 hours after pain onset and age 18-80 years


Persistent chest pain, cardiogenic shock, electrical instability, severe congestive heart failure and/or pulmonary edema, prior thrombolysis for index infarction, PCI within prior 30 days, stroke within prior three months, active bleeding or bleeding diatheses, recent trauma or major surgery in the prior month, relevant hematologic deviations, or malignancies

Primary Endpoints:

Infarct size at 5-10 days assessed by SPECT

Secondary Endpoints:

Composite of mortality, reinfarction, or stroke at 30 days

Drug/Procedures Used:

Patients were randomized to an invasive group (n=182) or conservative group (n=183). The invasive group underwent coronary angiography with or without PCI. Patients who underwent PCI were treated with abciximab. In the conservative group, patients were treated with conventional medical therapy, including unfractionated heparin infusion or subcutaneous low-molecular weight heparin. Following the randomized treatment, all patients were treated with clopidogrel 75 mg/day or ticlopidine 500 mg/day for at least four weeks, and aspirin 200-325 mg/day indefinitely.

Concomitant Medications:

Clopidogrel 300-600 mg or ticlopidine 500 mg; aspirin 500 mg; heparin 70 U/kg

Principal Findings:

Baseline characteristics were well balanced between the treatment groups, with 24% diabetics and 37% having an anterior infarction. The median time from chest pain onset to randomization was 23 hours. Among patients in the invasive group, 43% were patent (TIMI flow grade 2 or 3) on diagnostic angiography. Post-PCI TIMI grade 3 flow was present in 87% of patients in the invasive group.

The median time from randomization to angiography was 1.5 hours. Stents were used in 87% of the invasive group, percutaneous transluminal coronary angioplasty (PTCA) in 7%, and coronary artery bypass grafting (CABG) in 4%.

SPECT was performed in 95% of patients. The primary endpoint of infarct size by SPECT was smaller in the invasive group compared with the conservative management group (8% vs. 13%, p=0.0002). There was no difference in the composite endpoint of death, MI, or stroke at 30 days (4.4% in invasive group vs 6.6% in conservative group, p=0.37). There was also no difference in mortality at 30 days (1.6% for invasive group vs 3.8% for conservative group, p=0.21) or death or MI (4.4% vs. 6.0%, p=0.49). Unplanned PCI was performed in 33% of patients in the conservative group.


Among patients with ST elevation MI presenting longer than 12 hours after symptom onset and without persistent chest pain, treatment with an invasive strategy was associated with a reduction in infarct size at day 5-10 compared with a conservative management strategy.

Patients in the invasive group underwent angiography approximately 24 hours after symptom onset and the majority were treated with PCI. While there was a reduction in infarct size, there was no difference in the clinical composite endpoint at 30 days, although a larger study would likely be needed to detect a difference.

Current treatment guidelines for ST elevation MI do not recommend reperfusion in patients presenting longer than 12 hours from symptom onset without persistent symptoms.


Schömig A, et al. Mechanical Reperfusion in Patients With Acute Myocardial Infarction Presenting More Than 12 Hours From Symptom Onset. JAMA. 2005;293:2865-2872.

Presented by Dr. Adnan Kastrati at the March 2005 ACC Annual Scientific Session, Orlando, FL.

Clinical Topics: Anticoagulation Management, Cardiac Surgery, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Atherosclerotic Disease (CAD/PAD), Aortic Surgery, Interventions and Coronary Artery Disease, Interventions and Imaging, Angiography, Computed Tomography, Nuclear Imaging

Keywords: Coronary Artery Disease, Myocardial Infarction, Stroke, Tomography, Emission-Computed, Single-Photon, Heparin, Low-Molecular-Weight, Heparin, Ticlopidine, Immunoglobulin Fab Fragments, Angioplasty, Balloon, Coronary, Stents, Coronary Angiography, Chest Pain, Coronary Artery Bypass, Diabetes Mellitus

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