title: Fondaparinux and acute coronary syndromes: update on the OASIS 5-6 studies.
abstract: 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.
authors.affiliation: Department of Cardiology, University Hospital Jean-Minjoz, Besançon, France. francois.schiele@univ-fcomte.fr
authors.forename: François
authors.initials: F
authors.lastname: Schiele
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy*; D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use*; D002404:Catheterization / Q000009:adverse effects; D017984:Enoxaparin / Q000627:therapeutic use; D000077425:Fondaparinux; D006629:Hirudins; D006801:Humans; D010446:Peptide Fragments / Q000627:therapeutic use; D011134:Polysaccharides / Q000009:adverse effects / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use; D013927:Thrombosis / Q000209:etiology
chemical_list: D000925:Anticoagulants; D017984:Enoxaparin; D006629:Hirudins; D010446:Peptide Fragments; D011134:Polysaccharides; D011994:Recombinant Proteins; D000077425:Fondaparinux; C074619:bivalirudin
references.citation: Circulation. 1999 Oct 12;100(15):1593-601
references.pmid: 10517729
references.citation: J Am Coll Cardiol. 2006 Oct 3;48(7):1346-54
references.pmid: 17010793
references.citation: Eur Heart J. 2008 Dec;29(23):2909-45
references.pmid: 19004841
references.citation: N Engl J Med. 2001 Nov 1;345(18):1305-10
references.pmid: 11794149
references.citation: Lancet. 2008 May 10;371(9624):1559-61
references.pmid: 18468530
references.citation: Hematology. 2004 Oct-Dec;9(5-6):317-32
references.pmid: 15763970
references.citation: J Am Coll Cardiol. 2007 Oct 30;50(18):1742-51
references.pmid: 17964037
references.citation: Clin Appl Thromb Hemost. 2008 Jan;14(1):97-8
references.pmid: 18160576
references.citation: Eur Heart J. 2009 Jun;30(12):1457-66
references.pmid: 19351691
references.citation: N Engl J Med. 2006 Apr 6;354(14):1464-76
references.pmid: 16537663
references.citation: J Thromb Haemost. 2003 Jan;1(1):69-73
references.pmid: 12871541
references.citation: Chest. 2008 Jun;133(6 Suppl):670S-707S
references.pmid: 18574276
references.citation: Am Heart J. 2010 Feb;159(2):190-8
references.pmid: 20152216
references.citation: N Engl J Med. 2006 Apr 6;354(14):1477-88
references.pmid: 16537665
references.citation: Thromb Haemost. 1999 Feb;81(2):214-20
references.pmid: 10063994
references.citation: JAMA. 2004 Jul 7;292(1):45-54
references.pmid: 15238590
references.citation: Eur Heart J. 2007 Jul;28(13):1598-660
references.pmid: 17569677
references.citation: Chest. 2008 Jun;133(6 Suppl):708S-775S
references.pmid: 18574277
references.citation: N Engl J Med. 2008 May 22;358(21):2218-30
references.pmid: 18499566
references.citation: Circulation. 2008 Nov 11;118(20):2038-46
references.pmid: 18955665
references.citation: N Engl J Med. 2001 Nov 1;345(18):1298-304
references.pmid: 11794148
references.citation: N Engl J Med. 2008 Jun 5;358(23):2457-67
references.pmid: 18434646
references.citation: N Engl J Med. 2006 Nov 23;355(21):2203-16
references.pmid: 17124018
references.citation: Circulation. 2005 Mar 22;111(11):1390-7
references.pmid: 15781750
references.citation: Circulation. 2002 Nov 12;106(20):2550-4
references.pmid: 12427650
references.citation: J Am Coll Cardiol. 2007 Aug 14;50(7):e1-e157
references.pmid: 17692738
references.citation: Nature. 1999 Apr 1;398(6726):417-22
references.pmid: 10201371
references.citation: N Engl J Med. 1997 Aug 14;337(7):447-52
references.pmid: 9250846
references.citation: JAMA. 2006 Apr 5;295(13):1519-30
references.pmid: 16537725
references.citation: Eur Heart J. 2001 Sep;22(18):1716-24
references.pmid: 11511121
references.citation: Thromb Haemost. 2008 Oct;100(4):693-8
references.pmid: 18841294
references.citation: Lancet. 2008 Aug 16;372(9638):532-3; author reply 533-4
references.pmid: 18707977