Comparison Of Idraparinux With Vitamin K Antagonists For Prevention Of Thromboembolism In Patients With Atrial Fibrillation

Sanofi-aventis announced today that a weekly subcutaneous administration of idraparinux was as effective as warfarin, a Vitamin K Antagonist (VKA), in reducing stroke and non Central Nervous System (CNS) systemic embolic events in patients with atrial fibrillation (AF), a population at risk of thromboembolic events (TE). The results of the AMADEUS study were presented at the XXIst ISTH Congress (International Society on Thrombosis and Haemostasis) in Geneva. The AMADEUS trial, which enrolled a total of 4,576 patients with atrial fibrillation, met its primary endpoint. The event rate of the composite endpoint of any strokes (ischemic, hemorrhagic, and undefined) and non-CNS systemic embolism was 0.9% with idraparinux and 1.3% with warfarin (p= 0.007), meeting the criteria for non-inferiority. The incidence of clinically relevant bleeding, the primary safety outcome, was significantly higher in the idraparinux group than in the comparator group (19.7% vs. 11.3%, p<0.0001), although, overall no difference was observed in the all causes mortality between the two treatment groups. Bleeding appeared over time and was more pronounced in patients with impaired renal function and in the elderly. These observations indicate the need to consider a dose reduction of idraparinux depending on these characteristics in patients with AF. This will be addressed in the new BOREALIS-AF study that will compare the new neutralizable form of idraparinux (biotinylated idraparinux) to VKA in patients with atrial fibrillation and in which the dose will be adjusted depending on age and renal function after 7 weeks of treatment. Despite the early termination of the study due to the imbalance of bleeding events and low event rates, the trial succeeded in demonstrating the efficacy of idraparinux and met the criteria for non inferiority.
“With once a week idraparinux treatment we could have a convenient alternative to the cumbersome VKA treatment for patients suffering from atrial fibrillation recurrent complications.”' said Professor Harry Büller, from the University of Amsterdam’s Academic Medical Center Department of Vascular Medicine and principal investigator of the AMADEUS study. '“Nevertheless, the improvement of the safety profile while preserving efficacy should be addressed in the new BOREALIS-AF study with the once a week treatment with reversible biotinylated idraparinux, (a big step forward, well suited for a long acting agent) and dose adjustment according to patients characteristics.”' he added.