• Myocardial Infarction
• Cardiology Clinical Trials
• Interventional Techniques & Devices

• Myocardial Infarction
• Cardiology & Cardiovascular Medicine
• Cardiology Clinical Trials
• Interventional Techniques & Devices

The HORIZONS AMI trial showed that bivalirudin therapy in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous intervention (PCI) reduced mortality and bleeding for up to 3 years compared with heparin plus a glycoprotein IIb/IIIa inhibitor [Stone GW et al. N Engl J Med 2008]. According to Philippe Gabriel Steg, MD, Universite Paris-Diderot, Paris, France, who presented the results of the European Ambulance Acute Coronary Syndrome Angiography Trial [EUROMAX; Steg PG et al. N Engl J Med 2013], several issues remain, including the role of bivalirudin in the ambulance for patients triaged to primary PCI; the potential for reducing the risk of acute stent thrombosis with a prolonged bivalirudin infusion post-PCI; and the impact of contemporary practice (frequent use of radial arterial access and novel oral P2Y12 inhibitors) on the efficacy and safety of bivalirudin.

The objective of the EUROMAX trial was to examine whether bivalirudin, initiated in patients with STEMI while being transported in the ambulance for primary PCI, was superior to heparin and provisional use of glycoprotein IIb/IIIa inhibitors.

Patients with STEMI who presented within 12 hours after the onset of symptoms and were scheduled for primary PCI (n=2218) were randomized in the ambulance or at a non-PCI hospital to treatment with bivalirudin (0.75 mg/kg bolus followed by 1.75 mg/kg/hour infusion; n=1089) or to unfractionated heparin with or without a glycoprotein IIb/IIIa inhibitor (n=1109). To address prior concerns for increased acute stent thrombosis seen in patients treated with bivalirudin in the HORIZONS AMI trial, bivalirudin infusion in EUROMAX was continued post-PCI for at least 4 hours. Bailout use of a glycoprotein IIb/IIIa inhibitor was also allowed in the bivalirudin group if needed. During the course of the trial, the primary endpoint was changed. The original primary endpoint was the composite endpoint of death, reinfarction, or major bleeding. After a change in the study protocol, the primary and secondary endpoints were switched so that the primary endpoint was the composite of all-cause mortality or major bleeding at 30 days and the key secondary endpoint was mortality, reinfarction, or major bleeding at 30 days. The change in the primary endpoint was made in order to reduce the necessary sample size and occurred while the investigators were still unaware of study outcomes. Major bleeding was defined as intracranial, retroperitoneal, or intraocular bleeding; access-site hemorrhage requiring radiologic or surgical intervention; a reduction in the hemoglobin level of more than 4 g/dL (2.5 mmol/L) without an overt source of bleeding or a reduction in the hemoglobin level of more than 3 g/dL with an overt source of bleeding; reintervention for bleeding; or use of any blood-product transfusion that was not related to coronary artery bypass surgery.

Baseline characteristics were similar between the two groups, with the exception of diabetes (bivalirudin, 11.7% vs heparin, 15.3%; p<0.05) and prior MI (bivalirudin, 7.4% vs heparin, 10.2%; p<0.05). The primary endpoint occurred in 5.1% of patients treated with bivalirudin compared with 8.5% of those treated with heparin (RR, 0.60; 95% CI, 0.43 to 0.82; p=0.001).

The secondary endpoint occurred in 6.6% of the bivalirudin group versus 9.2% of the heparin group (RR, 0.72; 95% CI, 0.54 to 0.96; p=0.02). There was no significant difference between the bivalirudin and heparin groups in cardiac deaths (2.5% vs 3.0%; RR, 0.83; 95% CI, 0.50 to 1.38; p=0.48) and noncardiac deaths (0.5% vs 0.1%; RR, 5.09; 95% CI, 0.60 to 43.51; p=0.12). Major bleeding was reported in 2.6% of the bivalirudin groups versus 6.0% of the heparin group (RR, 0.43; 95% CI, 0.28 to 0.66; p<0.001). The composite endpoint of death, reinfarction, ischemia-driven reinfarction, stroke, and major bleeding was reported in 7.8% of the bivalirudin group compared with 10.6% of the heparin group (RR, 0.73; 95% CI, 0.56 to 0.96; p=0.02). The benefits of bivalirudin were consistent across the reported subgroups.

The rate of definite stent thrombosis within 24 hours was higher in the bivalirudin group (1.1%) compared with the heparin group (0.2%; RR, 6.11; 95% CI, 1.37 to 27.24; p=0.007).

The EUROMAX trial had several limitations, including its open-label design. Additionally, the trial was not powered to assess 30-day mortality.

This trial showed that in patients with STEMI who were being transported for primary PCI, the initiation of bivalirudin prior to hospital admission reduced the primary endpoint of death or bleeding and the secondary endpoint of death, bleeding, or reinfarction when compared with heparin. However, the rate of acute stent thrombosis was higher with bivalirudin compared with heparin-treated patients. The investigators attributed the benefits of bivalirudin to the substantial reduction in major bleeding. Prof. Steg concluded that these results support the use of bivalirudin for the prehospital management of STEMI prior to primary PCI.

• © 2013 MD Conference Express®