European Ambulance Acute Coronary Syndrome Angiography - EUROMAX

May 27, 2014
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Author/Summarized by Author:
Anthony A. Bavry, MD, MPH, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
The Medicines Company
Date Presented:
01/01/2013
Date Updated:
05/27/2014
Original Posted Date:
05/27/2014
References

Description:

The goal of the trial was to evaluate early treatment with bivalirudin compared with heparin (unfractionated or low-molecular weight) with optional glycoprotein IIb/IIIa inhibitor (GPI) among patients being transported for primary percutaneous coronary intervention (PCI).

Hypothesis:

Bivalirudin will reduce the frequency of major bleeding.

Study Design

  • Randomized
  • Parallel

Patient Populations:

Patients ≥18 years with STEMI being transported for primary PCI

Number of enrollees: 2,218
Duration of follow-up: 30 days
Mean patient age: 61 years
Percentage female: 25%

Exclusions:

  • Use of intravenous or oral anticoagulation prior to randomization
  • Recent surgery
  • History of major bleeding

Primary Endpoints:

  • Death or non-CABG major bleeding

Secondary Endpoints:

  • Death, reinfarction, or non-CABG major bleeding

Drug/Procedures Used:

Patients with ST-segment elevation myocardial infarction (STEMI) being transported for primary PCI were randomized in the ambulance to bivalirudin (n = 1,089) versus heparin (unfractionated or low-molecular weight) with optional GPI (n = 1,109).

Patients randomized to bivalirudin received a bolus of 0.75 mg/kg, then infusion of 1.75 mg/kg. Post-PCI, the infusion was to continue for 4 hours at 0.25 mg/kg. Bailout use of GPI was allowed.

Patients randomized to heparin could receive unfractionated heparin 100 U/kg without a GPI, unfractionated heparin 60 U/kg with a GPI, or enoxaparin 0.5 mg/kg with discretionary use of GPI.

Concomitant Medications:

P2Y12 inhibitor use was clopidogrel in 50%, prasugrel in 31%, and ticagrelor in 19%, which was given prior to angiography in 90%.

Principal Findings:

Overall, 2,218 patients were randomized. The median age was 61 years, 25% were women, and 12% had diabetes. Among the bivalirudin group, 3.9% received upstream GPI, while 7.6% received bailout GPI. Among the heparin group, 58.5% received upstream GPI, while 10.6% received bailout GPI. Radial artery access was used in 47.7% of the bivalirudin group versus 46.3% of the heparin group (p < 0.05). Thrombectomy was used in 32.2% of the bivalirudin group versus 31.5% of the heparin group (p = NS).

The primary outcome of death or major bleeding occurred in 5.1% of the bivalirudin group versus 8.5% of the heparin/GPI group (p = 0.001). More specifically, death or major bleeding occurred in 7.6% of the heparin with upstream GPI group and 9.8% of the heparin with bailout GPI group.

- Death, MI, or major bleeding: 6.6% vs. 9.2% (p = 0.03); respectively, for bivalirudin vs. heparin/GPI

- Major bleeding: 2.6% vs. 6.0% (p < 0.001), respectively

- Acute stent thrombosis: 1.1% vs. 0.2% (p = 0.007), respectively

- Death: 2.9% vs. 3.1% (p = NS), respectively

- Reinfarction: 1.7% vs. 0.9% (p = NS), respectively

Interpretation:

Among STEMI patients being transported for primary PCI, the early use of bivalirudin compared with heparin/GPI reduced the frequency of death or non–coronary artery bypass grafting (CABG) major bleeding. This was due to a reduction in major bleeding. Bivalirudin was associated with an increase in acute stent thrombosis.

This trial was similar to the design of HORIZONS-AMI, which also showed benefit with this strategy. However, this trial is in contrast to the HEAT-PPCI trial, which compared bivalirudin and bailout GPI with heparin, and bailout GPI with preprocedure ADP antagonist (ticagrelor > prasugrel > clopidogrel). HEAT-PPCI was a single-center trial, which documented an increase in adverse ischemic events, including stent thrombosis among the bivalirudin group, with no difference in major bleeding.

References:

Zeymer U, van't Hof A, Adgey J, et al. Bivalirudin is Superior to Heparins Alone With Bailout GP IIb/IIIa Inhibitors in Patients With ST-Segment Elevation Myocardial Infarction Transported Emergently for Primary Percutaneous Coronary Intervention: A Pre-Specified Analysis From the EUROMAX Trial. Eur Heart J 2014;May 21:[Epub ahead of print].

Gutierrez A, Bhatt DL. Balancing the Risks of Stent Thrombosis and Major Bleeding During Primary Percutaneous Coronary Intervention. Eur Heart J 2014;May 26:[Epub ahead of print].

Steg PG, van’t Hof A, Hamm CW, et al., on behalf of the EUROMAX Investigators. Bivalirudin Started During Emergency Transport for Primary PCI. N Engl J Med 2013;369:2207-17.

Presented by Dr. Philippe Gabriel Steg at the Transcatheter Cardiovascular Therapeutics meeting (TCT 2013), San Francisco, CA, October 30, 2013.

Keywords: Myocardial Infarction, Follow-Up Studies, Radial Artery, Heparin, Ticlopidine, Piperazines, Hirudins, Purinergic P2Y Receptor Antagonists, Stents, Percutaneous Coronary Intervention, Thrombectomy, Thrombosis, Enoxaparin, Recombinant Proteins, Peptide Fragments, Coronary Artery Bypass, Diabetes Mellitus, Hot Temperature, Platelet Glycoprotein GPIIb-IIIa Complex


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