Información del artículo
Resumen
Los antagonistas de la vitamina K (AVK) actualmente disponibles para la prevención del ictus en pacientes con fibrilación auricular tienen diversos inconvenientes, por su dificultad de manejo y riesgo de sangrado. Actualmente están en desarrollo diversos fármacos que serían posibles sustitutos de los AVK y que tienen grandes ventajas, siendo las principales la ausencia de necesidad de monitorización y las escasas interacciones farmacológicas y con los alimentos. Presentamos una revisión de los nuevos anticoagulantes orales que están en fases más avanzadas de investigación clínica, sus propiedades farmacológicas, ventajas y desventajas y los resultados en recientes ensayos clínicos.
Palabras clave:
Ictus
Fibrilación auricular
Anticoagulantes
Warfarina
Dabigatrán
Apixaban
Rivaroxaban
Abstract
The vitamin K antagonists (VKA) available for stroke prevention in patients with atrial fibrillation have many drawbacks due to their difficult clinical use and high risk of bleeding. Currently, several drugs are being developed as possible substitutes for VKA that have many advantages such as the lack of monitoring requirement and scarce pharmacologic and food interactions. The present article provides an update on the new oral anticoagulants that are in a more advanced stage of clinical research, their pharmacologic properties, advantages and disadvantages and their results in recent clinical trials.
Keywords:
Stroke
Atrial fibrillation
Vitamin K antagonists
Warfarin
Dabigatran
Apixaban
Rivaroxaba
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Bibliografía
[1.]
D. Wardrop, D. Keeling.
The story of the discovery of heparin and warfarin.
Br J Haematol, 14 (2008), pp. 757-763
[2.]
M. Di Nisio, S. Middeldorp, H.R. Büller.
Direct thrombin inhibitors.
N Engl J Med, 353 (2005), pp. 1028-1040
[3.]
SPORTIF Executive Steering Committee.
Ximelagatran vs warfarin for stroke prevention in patients with nonvalvular atrial fibrillation.
JAMA, 293 (2005), pp. 690-698
[4.]
W.G. Eisert, N. Hauel, J. Stangier, W. Wienen, A. Clemens, J. Van Ryn.
Dabigatran: an oral novel potent reversible nonpeptide inhibitor of thrombin.
Arterioscler Thromb Vasc Biol, 30 (2010), pp. 1885-1889
[5.]
Ficha técnica de dabigatrán. Disponible en: http://www.ema.europa.eu/docs/es_ES/document_library/EPAR_-_Product_Information/human/000829/WC500041059.pdf
[6.]
J. Van Ryn, J. Stangier, S. Haertter, K.H. Liesenfeld, W. Wiemen, M. Feuring.
Effect of dabigatran on coagulation assays and reversal strategies.
Thromb Haemost, 103 (2010), pp. 1116-1127
[7.]
K.H. Liesenfeld, H.G. Schäfer, I.F. Trocóniz, C. Tillmann, B.I. Eriksson.
Effects of the direct thrombin inhibitor dabigatran on ex vivo coagulation time in orthopaedic surgery patients: a population model analysis.
Br J Clin Pharmacol, 62 (2006), pp. 527-537
[8.]
J.C. Zikria, J. Ansell.
Oral anticoagulation with factor Xa and thrombin inhibitors: on the threshold of change.
Curr Opin Hematol, 16 (2009), pp. 347-356
[9.]
S. Schulman, N.R. Bijsterveld.
Anticoagulants and their reversal.
Transfus Med Rev, 21 (2007), pp. 37-48
[10.]
L. Chang.
Will symptomatic intracerebral hemorrhages decrease among eligible dabigatran-treated patients who receive intravenous tissue plasminogen activator for acute ischemic stroke?.
Arch Neurol, 67 (2010), pp. 1156-1157
[11.]
A. De Smedt, S. De Raedt, K. Niebooer, J. De Keyser, R. Brouns.
Intravenous thrombolysis with recombinant tissue plasminogen activator in a stroke patient treated with dabigatran.
Cerebrovasc Dis, 30 (2010), pp. 533-534
[12.]
M.C. Matute, M. Guillán, J. García-Caldentey, J. Buisan, M. Aparicio, J. Masjuan, et al.
Thrombolysis treatment for acute ischaemic stroke in a patient on treatment with dabigatran.
Thromb Haemost, 106 (2011), pp. 178-179
[13.]
S. Connolly, M. Ezekowitz, S. Yusuf, J. Eikelboom, and RE-LY Steering Committee and Investigators.
Dabigatran versus warfarin in patients with atrial fibrillation.
N Engl J Med, 361 (2009), pp. 1139-1151
[14.]
L. Wallentin, S. Yusuf, M. Ezekowitz, M. Alings, M. Flather, M.G. Franzosi, et al.
Efficacy and safety of dabigatran compared with warfarin at different levels of international normalised ratio control for stroke prevention in atrial fibrillation: an analysis of the RE-LY trial.
Lancet, 376 (2010), pp. 975-983
[15.]
H.C. Diener, S. Connoly, M.D. Ezekowitz, L. Wallentin, P.A. Reilly, S. Yang, et al.
Dabigatran compared with warfarin in patients with atrial fibrillation and previous transient ischaemic attack or stroke: a subgroup analysis of the RE-LY trial.
Lancet Neurol, 9 (2010), pp. 1157-1163
[16.]
FDA Cardiovascular and Renal Drugs Advisory Committee Application Dabigatran Briefing Document (2010). Disponible en: http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/CardiovascularandRenalDrugsAdvisoryCommittee/UCM226009.pdf
[17.]
F. Andreotti, T. Pafundi.
Los nuevos anticoagulantes y el futuro de la cardiología.
Rev Esp Cardiol, 63 (2010), pp. 1223-1229
[18.]
J.C. Zikria, J. Ansell.
Oral anticoagulation with factor Xa and thrombin inhibitors: on the threshold of change.
Curr Opin Hematol, 16 (2009), pp. 347-356
[19.]
M.M. Samama.
The mechanism of action of rivaroxaban — an oral, direct factor Xa inhibitor — compared with other anticoagulants.
Thromb Res, (2010),
[20.]
A. Turpie.
Oral, direct factor xa inhibitors in development for the prevention and treatment of thromboembolic diseases.
Arterioscler Thromb Vasc Biol, 27 (2007), pp. 1238-1247
[21.]
G.J. Hankey, J.W. Eikelboom.
Antithrombotic drugs for patients with ischaemic stroke and transient ischaemic attack to prevent recurrent major vascular events.
Lancet Neurol, 9 (2010), pp. 273-284
[22.]
S. Harder, J. Parisius, B. Picard-Willems.
Monitoring direct FXainhibitors and fondaparinux by prothrombinase-induced clotting time (PiCT): relation to FXa-activity and influence of assay modifications.
Thromb Res, 123 (2008), pp. 396-403
[23.]
M.R. Patel, K.W. Mahaffey, J. Garg, G. Pan, D.E. Singer, W. Hacke, ROCKET AF Investigators, et al.
Rivaroxaban versus warfarin in nonvalvular atrial fibrillation.
N Engl J Med, 365 (2011), pp. 883-891
[24.]
C. Roser-Jones, R.C. Becker.
Apixaban: an emerging oral factor Xa inhibitor.
J Thromb Thrombolysis, 29 (2010), pp. 141-146
[25.]
N. Raghavan, C.E. Frost, Z. Yu, K. He, H. Zhang, W.G. Humphreys, et al.
Apixaban metabolism and pharmacokinetics after oral administration to humans.
Drug Metab Disp, 37 (2009), pp. 74-81
[26.]
S.J. Connolly, J. Eikelboom, C. Joyner, H.C. Diener, R. Hart, S. Golitsyn, AVERROES Steering Committee and Investigators, et al.
Apixaban in patients with atrial fibrillation.
N Engl J Med, 364 (2011), pp. 806-817
[27.]
C.B. Granger, J.H. Alexander, J.J. McMurray, R.D. Lopes, E.M. Hylek, M. Hanna, ARISTOTLE Committees and Investigators, et al.
Apixaban versus warfarin in patients with atrial fibrillation.
N Engl J Med, 365 (2011), pp. 981-992
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