Expanding horizons of anticoagulant therapy: Dabigatran etexilate a novel oral anticoagulant
Keywords:
Dabigatran etexilate, Direct thrombin inhibitor, Novel anticoagulant, Stroke prevention, Atrial fibrillation, Venous thromboembolism, Orthopaedic surgeryAbstract
Thrombo-embolic disease is a major challenging clinical problem associated with significant mortality and morbidity. Anticoagulation with the existing heparin products and vitamin K antagonist (VKA) anticoagulants are still the mainstay of management. However, due to the risk of bleeding and well-documented drawbacks, the quest for a novel oral anticoagulant has led to the clinical development of dabigatran etexilate. Dabigatran etexilate is a direct thrombin (IIa) inhibitor which has recently been approved in India for prevention of venous thromboembolic events (VTE) in patients who have undergone major orthopaedic (total knee or hip replacement) surgery and for prevention of stroke, systemic embolism and reduction of vascular mortality in adult patients with atrial fibrillation. Thus dabigatran etexilate is a promising alternative to the current heparin products and VKAs in patients who require long-term oral anticoagulation.
References
Hawkins D. Limitations of traditional anticoagulants. Pharmacotherapy 2004;24:62S-65S.
Kaiser B. Oral antithrombin drugs. In: Kipshidze NN, Moses JW, Fareed J, Serruys PW, eds. Textbook of Interventional Cardiovascular Pharmacology. 1st ed. U.K: Informa Healthcare; 2007: 109-18.
Weitz JI. Bloood Coagulation and Anticoagulant, Fibrinolytic and Antiplatelet drugs. In: Brunton LL, Chabner BA, Knollmamn BC, eds. Goodman and Gillman's The Pharmacological Basis of Therapeutics. 12th ed. New York: McGraw Hill; 2011: 849-76.
Hauel NH, Nar H, Priepke H, Ries U, Stassen J-M, Wienen W. Structure-based design of novel potent nonpeptide thrombin inhibitors. J Med Chem 2002;45(9):1757-66.
Eisert WG, Hauel N, Stangier J, Wienen W, Clemens A, van Ryn J. Dabigatran: an oral novel potent reversible nonpeptide inhibitor of thrombin. Arterioscler Thromb Vasc Biol 2010;10:1885-9.
VanRyn J, Stangier J, Haertter S, Liesenfeld KH, Wienen W, Feuring M, et al. Dabigatran etexilate--a novel, reversible, oral direct thrombin inhibitor: interpretation of coagulation assays and reversal of anticoagulant activity. Thromb Haemost 2010;103(6):1116-27.
Hankey GJ, Eikelboom JW. Dabigatran etexilate: a new oral thrombin inhibitor. Circulation 2011;123(13):1436-50.
Blech S, Ebner T, Ludwig-Schwellinger E, Stangier J, Roth W. The metabolism and disposition of the oral direct thrombin inhibitor, dabigatran, in humans. Drug Metab Dispos 2008;36:386-99.
Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009;361(12):1139-51.
Connolly SJ, Ezekowitz MD, Yusuf S, Reilly PA, Wallentin L. Newly identified events in the RE-LY trial. N Engl J Med 2010;363:1875-6.
Patel P, Sangole N. New oral anticoagulants for stroke prevention in atrial fibrillation: Evidence from phase III clinical trials. Journal of Indian College of Cardiology 2012; 2(3):112-6.
Hori M, Connolly SJ, Zhu J, Liu LS, Lau CP, Pais P, Xavier D, et al. Dabigatran Versus Warfarin: Effects on Ischemic and Hemorrhagic Strokes and Bleeding in Asians and Non-Asians With Atrial Fibrillation. Stroke 2013;44(7):1891-1896.
Oldgren J, Budaj A, Granger CB, Khder Y, Roberts J, Siegbahn A, et al. Dabigatran vs. placebo in patients with acute coronary syndromes on dual antiplatelet therapy: a randomized, double-blind, phase II trial. Eur Heart J 2011;32(22):2781-9.
Eriksson BI, Dahl OE, Rosencher N, Kurth AA, van Dijk CN, Frostick SP, et al. Dabigatran etexilate versus enoxaparin for prevention of venous thromboembolism after total hip replacement: a randomised, double-blind, non-inferiority trial. Lancet 2007;370(9591):949-56.
Eriksson BI, Dahl OE, Rosencher N, Kurth AA, van Dijk CN, Frostick SP, et al. Oral dabigatranetexilate vs. subcutaneous enoxaparin for the prevention of venous thromboembolism after total knee replacement: the RE-MODEL randomized trial. J Thromb Haemost 2007;5(11):2178-85.
Ginsberg JS, Davidson BL, Comp PC, Francis CW, Friedman RJ, Huo MH, et al. Oral thrombin inhibitor dabigatran etexilate vs North American enoxaparin regimen for prevention of venous thromboembolism after knee arthroplasty surgery. J Arthroplasty 2009;24(1):1-9.
Eriksson BI, Dahl OE, Huo MH, Kurth AA, Hantel S, Hermansson K, et al. Oral dabigatran versus enoxaparin for thromboprophylaxis after primary total hip arthroplasty (RE-NOVATE II*). A randomised, double-blind, non-inferiority trial. Thromb Haemost 2011;105(4):721-9.
Tun NM, Oo TH. Prevention and Treatment of Venous Thromboembolism with New Oral Anticoagulants: A Practical Update for Clinicians. Thrombosis 2013;2013:183616.
Schulman S, Kearon C, Kakkar AK, Mismetti P, Schellong, S, Eriksson H, et al. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med 2009;361(24):2342-52.
Schulman S, Kakkar AK, Schellong SM, Goldhaber SZ, Eriksson H, Mismetti P, et al. A randomized trial of dabigatran versus warfarin in the treatment of acute venous thromboembolism (RE-COVER II) ASH Annual Meeting Abstracts. Blood 2011;118:205.
Schulman S. Treatment of venous thromboembolism with dabigatran. Curr Opin Pulm Med 2012;18(5):410-5.
Schulman S, Kearon C, Kakkar AK, Schellong S, Eriksson H, Baanstra D, et al. Extended use of dabigatran, warfarin, or placebo in venous thromboembolism. N Engl J Med 2013;368(8):709-18.
Schulman S. Treatment of venous thromboembolism with dabigatran. Curr Opin Pulm Med 2012;18(5):410-5.
U.S. Food and Drug Administration. FDA News release: FDA approves Pradaxa to prevent stroke in people with atrial fibrillation Available at: www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm230241.htm. Accessed 10 March 2013.
European Medicines Agency. Summary of the European Public Assessment Report (EPAR) for Pradaxa. Available at: http://www.emea.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/000829/human_med_000981.jsp. Accessed 10 March 2013.
The Central Drugs Standard Control Organization. New Delhi: Directorate General of Health Services, Ministry of Health and Family Welfare, Government of India. Available at: http://cdsco.nic.in/listofdrugapprovedmain.html. Accessed 10 March 2013.
Pradaxa (Dabigatran Etexilate) Indian prescribing information. Mumbai: Boehringer Ingelheim India; February 2013.
Global.pradaxa.com. Boehringer Ingelheim: Pradaxa® Summary of Product Characteristics, 2012. Available at: http://vte.pradaxa.com/content/dam/internet/pm/vte/com_EN/documents/SmPC Jan 2013 after Variation 44 2.doc.pdf. Accessed 4 June 2013.
Medsafe. New Zealand Medicines and Medical Devices Safety Authority: Pradaxa (Dabigatran etexilate) New Zealand Datasheet. Available at: http://www.medsafe.govt.nz/profs/datasheet/p/Pradaxacap.pdf. Accessed 1 August 2013.
Pharmac.govt.nz. New Zealand Datasheet: Pradaxa (Dabigatran etexilate). Available at: http://www.pharmac.govt.nz/2011/07/04/New%2520Zealand%2520Datasheet.pdf/text.
RELY-ABLE. Boehringer-Ingelheim and the PHRI, RELY-ABLE Trial Emergency Information: Background data on dabigatran. Available at: https://www.rely-able-trial.com/Rely2Web/resources/jsp/emergency/dabigatran_bg.jsp. Accessed 1 August 2013.