Fondaparinux and acute coronary syndromes: update on the OASIS 5–6 studies

摘要

Anticoagulant therapy is a major component in the management of acute coronary syndromes (ACS). Four anticoagulant agents are currently commercially available for ACS, namely unfractionated heparin (UFH), enoxaparin, bivalirudin and fondaparinux. We describe the advantages of fondaparinux and the reasons that have hampered its uptake into routine management of ACS. Fondaparinux was shown to be efficacious in the prevention of deep vein thrombosis vs low-molecular-weight heparins, while in the setting of venous thrombo-embolic disease, it was shown to be noninferior to enoxaparin and UFH. Two pivotal studies have demonstrated the efficacy of fondaparinux as an anticoagulant in the setting of ACS, namely OASIS-5 in non-ST elevation ACS, and OASIS-6 in ST elevation myocardial infarction (MI). In OASIS-5, fondaparinux was shown to be noninferior to enoxaparin in terms of death, MI or refractory ischemia at 9 days. Furthermore, a 50% reduction in bleeding complications was obtained with fondaparinux vs enoxaparin, leading to a risk reduction for death. In OASIS-6, fondaparinux was shown to be superior to the comparator (UFH or placebo). European and North American guidelines give fondaparinux a Grade 1A and 1B recommendation respectively, but uptake of fondaparinux in routine practice has been slow. We explore reasons for this, such as prevailing doubts about the efficacy of fondaparinux in the setting of angioplasty, the problem of catheter thrombosis, and the lack of antidote in case of bleeding complications. With the exception of primary angioplasty, fondaparinux is as effective as enoxaparin or UFH, but is also associated with a considerable reduction in bleeding complications, and thus, an undeniable net clinical benefit.