Fondaparinux in the contemporary pharmacotherapy Review article
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Abstract
Fondaparinux is a synthetic pentasaccharide that inhibits thrombin formation and thrombus development via selective antithrombin mediated inhibition of factor Xa. The excellent bioavailability (100%) and a long circulating half-life of 17 hours make it ideal for once-daily subcutaneous dosing. Excretion of fondaparinux is mainly renal and no need for laboratory monitoring is anticipated. Fondaparinux has been investigated for the prevention and treatment of arterial and venous thrombotic disorders and approved for use at a dose of 2,5 mg once-daily in the prevention and initial therapy of venous thromboembolism (VTE) at first in major orthopaedic surgery. Fondaparinux does not cross-react ex vivo with the anti-platelet antibodies responsible for heparin-induced thrombocytopenia but it still lacks approval for treating patients with HIT.
Two large trials involving approximately 32 000 patients recently evaluated fondaparinux in the treatment of non-ST elevation acute coronary syndromes (ACS) and ST elevation acute myocardial infarction. Fondaparinux was compared with enoxaparin or usual care, depending on the setting. A single, once-daily 2,5 mg subcutaneous dose of fondaparinux was used in both studies. The OASIS-5 and OASIS-6 trials demonstrated that fondaparinux significantly reduced death and reinfarctions and was associated with a substantial reduction in major bleeding compared with guideline recommended usual care. However, in the subgroup of primary percutaneous coronary interventions (PCIs) no clinical benefit of fondaparinux was found, but there were more catheter thrombosis and acute thrombotic complications. Care paths for the use of fondaparinux in patients with ACS are presented in this article based on current European and US management guidelines and available clinical evidence.
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