title: Recent pharmacological advances for treating venous thromboembolism: are we witnessing the demise of warfarin?
abstract: Vitamin K antagonists, such as warfarin, have been the mainstay in treatment and prophylaxis of venous thromboembolism. However, warfarin has many disadvantages including a narrow therapeutic window, numerous potential drug interactions, modulation of effect by alcohol and foods containing vitamin K and genetic variation in metabolism of warfarin, all of which contribute to the unpredictability of therapy. This has provided the impetus for developing new oral anticoagulants with a rapid onset of action, wide therapeutic window, predictable and reversible action, with few drug or dietary interactions, no requirement for routine coagulation monitoring or dose adjustment and acceptable cost. No single agent incorporates all these characteristics, but new factor Xa and direct thrombin inhibitors are being introduced into clinical practice that fulfil some of these aims. Here, we briefly discuss the current practice with its limitations and pitfalls, and then review important trials that have launched new oral anticoagulants into clinical practice.
authors.affiliation: Medical School, St. George's, University of London, London, SW17 0RE, UK.
authors.forename: Shankar
authors.initials: S
authors.lastname: Kumar
authors.forename: John
authors.initials: J
authors.lastname: Howell
authors.forename: Christopher
authors.initials: C
authors.lastname: Mattock
mesh_terms: D000925:Anticoagulants / Q000627:therapeutic use*; D000991:Antithrombins / Q000627:therapeutic use*; D015951:Factor Xa / Q000627:therapeutic use*; D006801:Humans; D010818:Practice Patterns, Physicians'; D013917:Thrombin / Q000037:antagonists & inhibitors; D054556:Venous Thromboembolism / Q000188:drug therapy* / Q000517:prevention & control; D014812:Vitamin K / Q000037:antagonists & inhibitors; D014859:Warfarin / Q000627:therapeutic use*
chemical_list: D000925:Anticoagulants; D000991:Antithrombins; D014812:Vitamin K; D014859:Warfarin; D013917:Thrombin; D015951:Factor Xa
keywords: dabigatran; idrabiotaparinux; reversal of anticoagulation; rivaroxaban; venous thromboembolism; warfarin
references.citation: Circulation. 2010 Apr 6;121(13):1523-32
references.pmid: 20368532
references.citation: Arterioscler Thromb Vasc Biol. 2012 Mar;32(3):563-8
references.pmid: 22345594
references.citation: Thromb Res. 2011 Jan;127 Suppl 2:S5-S12
references.pmid: 21193114
references.citation: N Engl J Med. 2010 Dec 23;363(26):2499-510
references.pmid: 21128814
references.citation: Circulation. 2011 Oct 4;124(14):1573-9
references.pmid: 21900088
references.citation: Thromb Haemost. 2011 Sep;106(3):429-38
references.pmid: 21800002
references.citation: Thromb Haemost. 2009 Jan;101(1):77-85
references.pmid: 19132192
references.citation: Haematologica. 2007 Feb;92(2):199-205
references.pmid: 17296569
references.citation: N Engl J Med. 2010 Nov 4;363(19):1791-800
references.pmid: 21047223
references.citation: J Thromb Haemost. 2008 Oct;6(10):1697-706
references.pmid: 18647228
references.citation: Lancet. 2008 Feb 2;371(9610):387-94
references.pmid: 18242412
references.citation: Chest. 2008 Jun;133(6 Suppl):381S-453S
references.pmid: 18574271
references.citation: Br J Haematol. 2012 Nov;159(4):427-9
references.pmid: 22970737
references.citation: N Engl J Med. 2009 Dec 10;361(24):2342-52
references.pmid: 19966341
references.citation: J Thromb Haemost. 2003 Jul;1(7):1504-14
references.pmid: 12871286
references.citation: J Thromb Thrombolysis. 2013 Aug;36(2):195-202
references.pmid: 23657589
references.citation: Chest. 2010 Jun;137(6):1382-90
references.pmid: 20081101
references.citation: Eur Heart J. 2006 Aug;27(16):1979-2030
references.pmid: 16885201
references.citation: Pharmacol Ther. 2011 Apr;130(1):46-58
references.pmid: 21185864
references.citation: N Engl J Med. 2012 Apr 5;366(14):1287-97
references.pmid: 22449293
references.citation: Lancet. 2012 Jan 14;379(9811):123-9
references.pmid: 22130488
references.citation: Thromb Haemost. 2007 Oct;98(4):756-64
references.pmid: 17938798
references.citation: Chest. 2008 Jun;133(6 Suppl):160S-198S
references.pmid: 18574265