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Otamixaban reduced major coronary complications in acute coronary syndrome
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Results from the phase-2 SEPIA-ACS1 TIMI 42 trial showed that intermediate doses of otamixaban, an IV direct Factor Xa inhibitor, produced the best results for patients with non-ST-elevation acute coronary syndromes.
Marc S. Sabatine, MD, MPH, a cardiologist at Brigham and Women’s Hospital, presented the results during the European Society of Cardiology Congress 2009 in Barcelona. Results were also published online in The Lancet.
According to Sabatine, lower doses of the drug, 0.035 mg/kg per hour and 0.70 mg/kg per hour, resulted in inadequate coagulation and higher rates of thrombotic complications during percutaneous coronary intervention. The highest dose, 0.175 mg/kg per hour, resulted in excessive bleeding.
“However, intermediate doses decreased the risk for death or ischemic events with a comparable risk of major or minor bleeding compared with unfractionated heparin and eptifibatide,” he said.
To explore the optimal dose of otamixaban, researchers in 36 countries enrolled 3,241 patients into the randomized, double blind, phase-2, parallel group clinical trial. Patients were assigned to one of five doses of otamixaban: 0.035 mg/kg per hour, 0.70mg/kg per hour, 0.105 mg/kg per hour, 0.140 mg/kg per hour or 0.175 mg/kg per hour. As a control group, 449 patients were assigned to unfractionated heparin and eptifibatide.
The primary endpoint was rate of death, second myocardial infarction or additional complications seven days after treatment.
Otamixaban superior
Sabatine said that the primary endpoint was superior in patients assigned otamixaban compared with those assigned heparin. The only exception was in the lowest dose arm (0.035 mg/kg per hour), which was stopped by the data monitoring committee.
“In particular, treatment with intermediate doses of otamixaban — 0.105 or 0.140 mg/kg per hour — resulted in a 40% decrease in the rate of the primary endpoint,” Sabatine said. “This benefit persisted over 180 days.”
Rates of death or MI were low for all patients assigned to otamixaban, except those in the lowest dose group. Rates ranged from 2.6% in the group assigned 0.035 mg/kg per hour group to 2.8% in the 0.175 mg/kg per hour and 0.70 mg/kg per hour groups. The rate was 2.7% in the 0.140 mg/kg per hour group.
The rate of death or MI was 4.9% in the control group. Sabatine said patients in the intermediate doses had 46% reduction in risk for death or MI.
“Otamixaban at 0.105 or 0.140 mg/kg per hour appears to be the best range for further study as a replacement for unfractionated heparin plus a glycoprotein IIb/IIIa inhibitor for in the setting of treatment for non-ST-elevation acute coronary syndrome,” Sabatine said in conclusion.
Sabatine MS. Lancet. 2009; doi:10.1016/S0140-6736(09)61454-9.