Otamixaban may be a useful alternative treatment for patients with acute coronary syndromes (sepia-acs1 timi 42 study)

Otamixaban may be a useful alternative treatment for patients with acute coronary syndromes (sepia-acs1 timi 42 study)

An article published Online First and in a future edition of The Lancet reports that otamixaban is a potential new agent for patients with acute coronary syndromes, such as heart attacks or sudden worsening of angina. The article is the work of Dr Marc S Sabatine, TIMI Study Group, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA, and colleagues. It is being presented at the European Society of Cardiology meeting, Barcelona.

'Non-ST-elevation acute coronary syndromes' occur when fatty plaques in coronary arteries break. This leads to a thrombus which is the formation of a small blood clot within the artery. This results in a blocking of the blood flow to the heart muscle. A molecule called Factor Xa is a crucial component in the pathway leading to thrombus formation. Otamixaban is a drug which inhibits factor Xa. The current conventional treatment for these patients is unfractionated heparin. This treatment option has a number of disadvantages, including thinning the blood to an unpredictable degree and for that reason it requires frequent monitoring. The authors in this study compared a range of otamixaban doses with unfractionated heparin and eptifibatide, an intravenous glycoprotein IIb/IIIa platelet inhibitor, the combination of which represents current standard of care for acute coronary syndromes.

A total of 3,241 patients from 196 sites in 36 countries were included in this randomized, double-blind, phase 2 trial. They all had non-ST-elevation acute coronary syndromes. Patients were assigned to one of five doses of otamixaban (0•08 mg/kg bolus followed by infusions of 0•035 [n=125], 0•070 [676], 0•105 [662], 0•140 [658], or 0•175 [671] mg/kg/h) or to a control of unfractionated heparin (60 IU/kg intravenous bolus followed by an infusion of 12 IU/kg/h) plus eptifibatide (180 μg/kg intravenous bolus followed by an infusion of 1•0-2•0 μg/kg/min [n=449]. Enrolment into the lowest dose group was stopped early at the recommendation of the Data Monitoring Committee. This was due to elevated numbers of patients going on to have full heart attacks and or dying. The primary efficacy endpoint was a combination of death, heart attack, urgent treatment to increase blood flow in the artery, or bailout glycoprotein IIb/IIIa inhibitor use up to seven days. The primary safety endpoint was major or minor bleeding not associated to coronary-artery bypass grafting.

Findings indicated that in all of the otamixaban dosage groups, the rate of death, second heart attack, or additional coronary complications tended to be inferior with otamixaban than with heparin plus eptifibatide. This was not the case in the lowest otamixaban dosage group. In particular, patients receiving an intermediate dose of otamixaban (0.105 or 0.140 mg/kg/hr) had a 40 percent lower rate of death, second heart attack, or additional coronary complications than those treated with the existing standard of care - heparin plus eptifibatide. In addition, these patients had a 46 percent reduction in death or a second heart attack. These benefits persisted during 180 days. There was a considerable increase in bleeding across the five otamixaban dosage groups. However, the rate in intermediate doses of otamixaban (0.105 or 0.140 mg/kg/hr) was comparable to the rate in patients treated with heparin plus eptifibatide.

The authors write in conclusion: "Treatment with otamixaban at doses of 0•105 or 0•140 mg/kg/h was associated with a 40% reduction in death or ischaemic complications compared with unfractionated heparin plus eptifibatide... Our study offers additional preliminary evidence for the efficacy and safety of direct factor Xa inhibition with otamixaban in patients with coronary disease."

They continue by saying: "These findings will need to be tested in a large phase III trial to establish the definitive role of otamixaban in the treatment of acute coronary syndromes."

In an associated note, Dr John W Eikelboom, McMaster University, Hamilton, ON, Canada, and Dr Jeffrey I Weitz, McMaster University and Henderson Research Centre, Hamilton, ON, Canada, point out that with other drugs available such as bivalirudin, the need for new intravenous agents such as otamixaban is minimal.

They comment: "These findings suggest that, like bivalirudin, otamixaban may be a useful alternative to heparin for patients with acute coronary syndromes who are undergoing PCI. However, do we need another parenteral agent for this indication? Without safety or convenience advantages, otamixaban would need to demonstrate efficacy that is superior not only to heparin, but also to bivalirudin, before it would be adopted for clinical use. To our knowledge, there are no ongoing phase 3 trials to explore these possibilities, nor is otamixaban under development for other clinical indications."

"Otamixaban for the treatment of patients with non-ST-elevation acute coronary syndromes (SEPIA-ACS1 TIMI 42): a randomised, double-blind, active-controlled, phase 2 trial"

Marc S Sabatine, Elliott M Antman, Petr Widimsky, Iftikhar O Ebrahim, Robert G Kiss, André Saaiman, Rostislav Polasek, Charles F Contant, Carolyn H McCabe, Eugene Braunwald

DOI: 10.1016/S0140-6736(09)61454-9

The Lancet

NUR2106 Group 8 - Acute Coronary Syndrome: Unstable Angina - Patient: Dominic (Video Medical And Professional 2020).

Section Issues On Medicine: Cardiology