Fondaparinux anticoagulation less intense, more predictable than enoxaparin
MedWire News: The less intense and more predictable anticoagulant effect of fondaparinux may explain the drug’s lower rates of bleeding and improved efficacy compared with enoxaparin observed in the Organization to Assess Strategies In acute ischemic Syndromes (OASIS)-5 trial, researchers report.
“In the OASIS-5 trial, fondaparinux reduced major bleeding with similar short-term efficacy as enoxaparin but lowered death and stroke during long-term follow-up,” explain John Eikelboom (McMaster University, Hamilton, Ontario, Canada) and colleagues.
To investigate the mechanism of lower bleeding and improved efficacy with fondaparinux, Eikelboom and team compared the relative anticoagulant intensities in plasma samples collected 6, 24, and 72 hours after the first dose of the study drug in 48 patients with acute coronary syndrome (ACS) randomly assigned to receive fondaparinux 2.5 mg/day and 42 patients assigned to receive enoxaparin 1 mg/kg twice daily.
They measured anti-factor (F)Xa concentration to reflect drug levels, FXa clot time to reflect anticoagulant effect, and endogenous thrombin potential (ETP), which is a global test of hemostatic function.
Six hours after the drugs were administered, the researchers found that the mean anti-FXa level and FXa clot time were both approximately 50% lower among patients given fondaparinux compared with those assigned to receive enoxaparin, at 0.52 versus 1.2 IU/ml and 64.9 versus 111.8 seconds, respectively.
In addition, patients assigned to receive fondaparinux had a significantly higher ETP area under the curve (AUC) than those assigned to enoxaparin (386.7 vs 206.4 mA). These differences remained evident at 24 and 72 hours.
The researchers also observed significantly less variability in anti-Xa levels, Xa clot time, and ETP AUC for fondaparinux-treated patients compared with those given enoxaparin at 6 hours.
“These results most likely explain the reduced risk for bleeding seen with fondaparinux compared with enoxaparin in the OASIS-5 trial and suggest that a lower intensity of anticoagulation than used in the past may be sufficient to prevent recurrent ischemic events and death in patients with ACS who are concurrently treated with aspirin and clopidogrel,” conclude Eikelboom et al in the Journal of Thrombosis and Haemostasis.
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By Laura Dean