BRAVE: Bavarian Reperfusion Alternatives Evaluation -- Reteplase Plus Abciximab or Abciximab Alone Prior to PCI in AMI Patients

Luis Gruberg, MD, FACC


December 30, 2003

Editorial Collaboration

Medscape &

Presenter: Adnan Kastrati, MD; Deutsches Herzzentrum, Munich, Germany

Percutaneous coronary intervention (PCI) is superior to thrombolysis in patients with acute myocardial infarction (AMI). However, there is an unavoidable delay between the diagnosis of the AMI and the time when the percutaneous intervention is performed, particularly when a patient presents at a hospital that doesn't have an on-site cath lab.

Intended to combine the wide availability and speed of pharmacologic agents with the known benefits of mechanical reperfusion, the concept of facilitated PCI is defined as a chemical reperfusion strategy using a half dose of thrombolytic therapy, with or without a glycoprotein (GP) IIb/IIIa inhibitor, prior to PCI.


The Bavarian Reperfusion Alternatives Evaluation (BRAVE) was conducted to assess whether reteplase (Retavase, Centocor, Inc; Malvern, Pennsylvania) plus abciximab (ReoPro, Eli Lilly; Indianapolis, Indiana) ("combo therapy") is more effective than abciximab alone when given as pretreatment to AMI patients referred for primary PCI.


This open-label study randomized patients to 1 of 2 arms: (1) a half dose of reteplase (2 boluses of 5 U half an hour apart) in combination with abciximab as a bolus (0.25 mg/kg) followed by a 12-hour infusion (0.125 mg/kg/min).; or (2) abciximab only.

Inclusion Criteria
  • Patients with ST-segment elevation AMI admitted within 12 hours of onset of symptoms

  • Chest pain lasting ≥ 20 min

Exclusion Criteria
  • Malignancies

  • Prolonged resuscitation

  • Previous stroke within the last 3 months

  • Bleeding diathesis

  • PCI in the 30 days preceding the AMI

  • Oral anticoagulation with coumadin

  • Severe uncontrolled hypertension

Primary Endpoint
  • Final infarct size (as percentage of left ventricle) by scintigraphic study performed 5-10 days after randomization. (The study was designed to have 80% power for detecting a 30% reduction in infarct size in patients treated with the combination approach.)

Secondary Endpoints
  • Death, recurrent , hemorrhagic stroke

  • Major bleeding


A total of 253 patients underwent randomization to either reteplase plus abciximab (n = 128) or abciximab alone (n = 125). All patients were transferred to the cath lab for angiography. The majority of these patients (74%) were recruited at community hospitals without cath lab facilities and were transferred to a PCI center (average distance 39 km). Baseline characteristics were well balanced between the 2 groups (Table).

Table. BRAVE: Baseline Clinical Characteristics
Characteristic Reteplase + Abciximab
(n = 128)
Abciximab Alone
(n = 125)
Age (yrs) 63 62
Male gender (%) 78 74
Diabetes (%) 19 23
Current smoker (%) 42 41
Hypertension (%) 56 52
Hyperlipidemia (%) 63 66
Anterior MI (%) 45 39
Killip class I-II (%) 98 98
Time to randomization (hrs) 3.0 (2.0-5.9) 2.8 (1.8-6.8)
Infarct location (%)    
Anterior 45 39
Inferior 42 52
Lateral 13 9

TIMI flow rates at baseline angiography were significantly better in patients randomized to the combination therapy; 40% of these patients had a TIMI flow 3 compared with only 18% in patients treated with abciximab alone (Figure 1). Final TIMI 3 flow rates were achieved in 87% of both groups at the end of the procedure (Figure 2). More than 90% of the patients were treated with stents in both groups.

Figure 1. BRAVE: TIMI flow rates at initial angiography.
Figure 2. BRAVE: final TIMI flow rates.

SPECT scan was performed in > 90% of patients in both groups at an average of 6 days after the infarction. There was no difference in infarct size (primary endpoint) between the 2 groups (Figure 3). Furthermore, at 30 days, there was also no significant difference in the secondary endpoints of death, MI, stroke, or major bleeding complications between the 2 groups (Figure 4). Analysis of different subsets of patients showed that there was no difference in the primary endpoint in transferred patients or in patients treated within 2 hours.

Figure 3. BRAVE: infarct size by SPECT.
Figure 4. BRAVE: clinical events at 30 days.

Investigators concluded from the findings of the BRAVE study that pretreatment with reteplase plus abciximab is not superior to abciximab alone in patients with AMI referred for primary PCI.

Commentary: Frans Van De Werf, Gasthuisberg University Hospital, Leuven, Belgium

Previous studies have shown that primary PCI in AMI patients is superior to thrombolytic therapy, even if patients had to be transferred to a tertiary care hospital where PCI can be performed. As shown in these studies, the time to balloon first inflation is critical. Unfortunately, although in the majority of trials the time to balloon is rather short, in the real world the time to balloon is delayed. Therefore, a strategy of pharmacologic reperfusion while the patient is waiting for intervention or is being transported to another facility makes sense.

In the present study, although patients treated with combination therapy had better TIMI 3 flow rates, it did not translate into a significant reduction in infarct size. This may be explained by the rather low rate of TIMI 3 flow obtained in the present study (40%). In other studies, TIMI 3 flow rates have been observed in > 55% of patients treated with this combination. Current ongoing trials will provide further data on the value of facilitated PCI. At present we do not have clear evidence that facilitated PCI provides any advantage in AMI patients.

Editorial Commentary

This was an excellent study that failed to provide evidence that facilitated PCI with a combination of thrombolytic therapy and GP IIb/IIIa inhibitors has an immediate effect on infarct size. Conversely, as stated by Prof. Van De Werf, patients treated with this combination had a significantly better initial TIMI 3 flow rate, which has been shown in the past to be an excellent predictor of outcome, but comes at the price of higher bleeding complications. It would be interesting to see whether there is any impact of this treatment on long-term outcomes; however, it was not stipulated in the endpoints of the study.