The Medicines Company (NASDAQ: MDCO) today announced results from the EUROMAX Trial, a 2,218 patient Phase IIIb randomized study of the Company's Angiox® (bivalirudin), which is marketed as Angiomax® (bivalirudin) in the US. The trial met its pre-specified primary and secondary endpoints, including statistically significant reductions in the primary composite endpoint of death and major bleeding among patients randomized to Angiox. Results were presented as a Late-Breaking Clinical Trial at the 25th annual Transcatheter Cardiovascular Therapeutics (TCT) Scientific Symposium and were published simultaneously in The New England Journal of Medicine.
The EUROMAX trial compared administration of Angiox to heparin or low-molecular weight heparin (heparins) with optional glycoprotein inhibitors (GPI) started during emergency transport in patients with STEMI, the most severe form of heart attack, undergoing primary percutaneous coronary intervention (PCI).
Patients treated with Angiox vs. heparins showed a:
- 40% relative risk reduction (5.1% vs. 8.5%, p=0.001) in the primary composite endpoint of death and non-CABG related bleeding 30 days after their PCI
- 28% relative risk reduction in the principal secondary composite outcomes of death, re-infarction or major bleeding (6.6% vs. 9.2%, p=0.02)
- 57% relative risk reduction of major bleeding (2.6% vs. 6.0%, p < 0.001).
Principal Investigator, lead author and presenter, Professor P. Gabriel Steg, MD, of Hôpital Bichat in Paris, said, "EUROMAX was a large, international, randomized trial in AMI management with early triage and initiation of therapy, in a contemporary treatment setting in which half the patients underwent PCI via the radial access approach and received either prasugrel or ticagrelor, one of the new P2Y12 inhibitors. These results pave the way for routine use of bivalirudin as an anticoagulant during the pre-hospital phase of acute myocardial infarction management, during transport of patients for emergency primary angioplasty."
Efthymios N. Deliargyris, MD, Vice President and Global Medical Director of The Medicines Company, said, ''EUROMAX provides further evidence of the clinical utility of Angiox in contemporary PCI for acute myocardial infarction, with results highly consistent with the observations from the HORIZONS-AMI trial."
The risk of acute stent thrombosis was higher in patients treated with bivalirudin vs. heparins (1.1% vs. 0.2%; relative risk, 6.11, p = 0.007). The investigators noted in The New England Journal of Medicine paper, ''Given the delayed onset of the anti-platelet effect of the oral P2Y12 inhibitors in STEMI, avoiding the occurrence of stent thrombosis may require more potent and rapidly effective anti-thrombotic agents, such as intravenous anti-platelet drugs."
Simona Skerjanec, Senior Vice President of Cardiovascular Medicines at The Medicines Company, added, ''EUROMAX demonstrates our ongoing efforts to perform rigorous clinical trials and demonstrates our commitment to advancing acute cardiovascular care globally to save lives, alleviate suffering and contribute to the economics of healthcare."
About EUROMAX
EUROMAX (EUROpean aMbulance Acs angioX trial) is a 2,218 randomized, controlled, open label, international, multicenter study that compared early administration of Angiox to unfractionated or low-molecular-weight heparin with optional glycoprotein inhibitors (GPI). Patients with ST-segment elevation myocardial infarction (STEMI) who were being transported for primary percutaneous coronary intervention (PCI) received either bivalirudin or unfractionated or low-molecular-weight heparin with optional GPI (control group). At 30 days, the primary outcome was a composite of death or major bleeding not associated with coronary-artery bypass grafting (CABG), and the principal secondary outcome was a composite of death, reinfarction, or non-CABG major bleeding. Patients who were assigned to the bivalirudin group received a bolus of 0.75 mg per kilogram, followed by an infusion of 1.75 mg per kilogram per hour, which should be continued for at least 4 hours after PCI. The protocol also specified that the dose during the post-PCI interval should be 0.25 mg per kilogram per hour; however, continuation of the higher dose used during PCI was also permitted. Bailout use of a GPI was allowed in the event of giant thrombus or no-reflow.
About Angiox/Angiomax
In Europe, Angiox currently is indicated as an anticoagulant for adult patients undergoing PCI, including patients with STEMI undergoing primary PCI. Angiox is also indicated for the treatment of adult patients with unstable angina/non-STEMI planned for urgent or early intervention. Please see full prescribing information available at http://www.angiox.com.
In the United States, bivalirudin is marketed under the trade name Angiomax and is indicated in patients undergoing PCI with provisional use of GPI and in patients with, or at risk of, heparin-induced thrombocytopenia and thrombosis syndrome (HIT/HITTS) undergoing PCI. In addition, Angiomax is also indicated for use as an anticoagulant in patients with UA undergoing percutaneous transluminal coronary angioplasty (PTCA). Angiomax is intended for use with aspirin. Angiomax is not approved for use in patients with acute coronary syndromes (ACS) not undergoing PCI or PTCA.
In clinical trials comparing Angiomax and heparin, the most common adverse reaction for Angiomax was bleeding (28%). Other common adverse reactions were headache, thrombocytopenia and fever. An unexplained fall in blood pressure or hematocrit, or any unexplained symptom, should lead to serious consideration of a hemorrhagic event and cessation of Angiomax administration. Angiomax should be used with caution in patients with disease states associated with an increased risk of bleeding.
In gamma brachytherapy, an increased risk of thrombus formation, including fatal outcomes, has been associated with the use of Angiomax. Angiomax is contraindicated in patients with active major bleeding or hypersensitivity to Angiomax or its components.