Metrika članka

  • citati u SCindeksu: 0
  • citati u Google Scholaru:[=>]
  • posete u prethodnih 30 dana:178
  • preuzimanja u prethodnih 30 dana:174
članak: 1 od 1  
Medicinski časopis
2012, vol. 46, br. 3, str. 145-154
jezik rada: srpski
vrsta rada: pregledni članak
doi:10.5937/mckg46-1612


Novi antikoagulantni lekovi
aUniverzitet u Beogradu, Farmaceutski fakultet, Institut za farmakologiju
bUniverzitet u Beogradu, Medicinski fakultet, Klinički centar Srbije
cInstitut za kardiovaskularne bolesti 'Dedinje', Beograd + Medicinski fakultet, Beograd

e-adresa: aleksn@pharmacy.bg.ac.rs

Sažetak

Antikoagulantni lekovi su delotvorni u prevenciji i lečenju tromboze i tromboembolijskih komplikacija, koje su čest uzrok morbiditeta i mortaliteta. Ipak, uprkos kliničkoj delotvornosti, standardni antikoagulansi poseduju značajne nedostatke. Zbog toga, modulacija procesa koagulacije danas predstavlja značajnu metu za razvoj novih, oralnih i parenteralnih, antikoagulanasa. Novi oralni antikoagulansi deluju selektivno na trombin (ksimelagatran, dabigatran eteksilat) ili na faktor koagulacije Xa (rivaroksaban, apiksaban, edoksaban). Za razliku od standardnih antikoagulanasa, antagonista vitamina K, imaju brz početak dejstva i relativno veliku terapijsku širinu, ne zahtevaju laboratorijsku kontrolu protrombinskog vremena (PT), i retko stupaju u interakcije sa hranom i lekovima. Novi parenteralni antikoagulansi svoje antikoagulantno dejstvo ostvaruju indirektnom (semuloparin, idrabiotaparinuks) ili direktnom inhibicijom faktora Xa (otamiksaban), kao i inhibicijom faktora koagulacije IXa (RB006). Glavne karakteristike ovih lekova su brz početak dejstva i predvidljiv antikoagulantni efekat, a kod većine je moguće postići brzu neutralizaciju adekvatnim antidotom.

Ključne reči

Reference

*** (2012) Bayer's Xarelto (rivaroxaban) granted priority review by US FDA to prevent secondary cardiovascular events in patients with ACS. Leverkusen: Bayer AG, http://www.bayer.com/en/news-detail.aspx?newsid=15745
*** (2011) Evaluation of weekly subcutaneous Biotinylated idraparinux versus oral adjusted-dose Warfarin to prevent stroke and systemic thromboembolic events in patients with atrial Fibrillation (BOrealiS-aF). Bethesda: Service of U.S. national institutes of health, ClinicalTrials.gov, h
*** (2009) Sanofi-aventis provides an R&D. Paris: Sanofi-aventis press, release, http://en.sanofi.com/images/14031_20091221_rdupdate_en.pdf
Ahrens, I., Lip, G.Y.H., Peter, K. (2010) New oral anticoagulant drugs in cardiovascular disease. Thrombosis and haemostasis, 104(1): 49-60
Albers, G.W., Diener, H., Frison, L., Grind, M., Nevinson, M., Partridge, S., Halperin, J.L., Horrow, J., Olsson, B.S., Petersen, P., Vahanian, A. (2005) Ximelagatran vs warfarin for stroke prevention in patients with nonvalvular atrial fibrillation: A randomized trial. JAMA, 293(6): 690-8
Alexander, J.H., Lopes, R.D., James, S., Kilaru, R., He, Y., Mohan, P., Bhatt, D.L., Goodman, S., Verheugt, F.W., Flather, M., Huber, K., Liaw, D., Husted, S.E., Lopez-Sendon, J. (2011) Apixaban with antiplatelet therapy after acute coronary syndrome. N Engl J Med, 365(8): 699-708
Bauer, K.A. (2011) Recent progress in anticoagulant therapy: Oral direct inhibitors of thrombin and factor Xa. J Thromb Haemost, 9 (Suppl 1): 12-19
Bauersachs, R., Berkowitz, S.D., Brenner, B., Buller, H.R., Decousus, H., Gallus, A.S., Lensing, A.W., Misselwitz, F., Prins, M.H., Raskob, G.E., Segers, A. (2010) Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med, 363(26): 2499-510
Bauersachs, R.M. (2012) Use of anticoagulants in elderly patients. Thrombosis research, 129(2): 107-15
Beasley, N.B., Unger, E.F., Temple, R. (2011) Anticoagulant options: Why the FDA approved a higher but not a lower dose of dabigatran. N Engl J Med, 364(19): 1788-90
Büller, H.R., Gallus, A.S., Pillion, G., Prins, M.H., Raskob, G.E. (2012) Enoxaparin followed by once-weekly idrabiotaparinux versus enoxaparin plus warfarin for patients with acute symptomatic pulmonary embolism: A randomised, double-blind, double-dummy, non-inferiority trial. Lancet, 379(9811): 123-129
Colwell, C.W., Berkowitz, S.D., Lieberman, J.R., Comp, P.C., Ginsberg, J.S., Paiement, G., McElhattan, J., Roth, A.W., Francis, C.W. (2005) Oral direct thrombin inhibitor ximelagatran compared with warfarin for the prevention of venous thromboembolism after total knee arthroplasty. Journal of bone and joint surgery. American volume, 87(10): 2169-77
Connolly, S.J., Ezekowitz, M.D., Yusuf, S., Eikelboom, J., Oldgren, J., Parekh, A., Pogue, J., Reilly, P.A., Themeles, E., Varrone, J., Wang, S., Alings, M., Xavier, D., Zhu, J., i dr. (2009) Dabigatran versus warfarin in patients with atrial fibrillation. New England journal of medicine, 361(12): 1139-51
Connolly, S.J., Eikelboom, J., Joyner, C., Diener, H., Hart, R., Golitsyn, S., Flaker, G., Avezum, A., Hohnloser, S.H., Diaz, R., Talajic, M., Zhu, J., Pais, P., Budaj, A., Parkhomenko, A. (2011) Apixaban in patients with atrial fibrillation. N Engl J Med, 364(9): 806-17
Deloughery, T.G. (2011) Practical aspects of the oral new anticoagulants. American Journal of Hematology, 86(7): 586-590
Douketis, J.D. (2011) Dabigatran as anticoagulant therapy for atrial fibrillation. Pol arch med wewn, 121: 73-80
Dunn, W. (2008) Simulation About Safety, Not Fantasy. CHEST Journal, 133(1): 6
Eikelboom, J.W., Weitz, J.I. (2010) New Anticoagulants. Circulation, 121(13): 1523-1532
Elezović, I. (2004) Antikoagulantni lekovi. u: Kažić T., Ostojić M. [ur.] Klinička kardiovaskularna farmakologija, Integra, 339-364
Eriksson, B.I., Dahl, O.E., Rosencher, N., Kurth, A.A., van Dijk, C.N., Frostick, S.P., Kälebo, P., Christiansen, A.V., Hantel, S., Hettiarachchi, R., Schnee, J., Büller, H.R. (2007) Oral dabigatran etexilate vs. subcutaneous enoxaparin for the prevention of venous thromboembolism after total knee replacement: The RE-MODEL randomized trial. Journal of thrombosis and haemostasis, 5(11): 2178-85
Eriksson, B.I., Dahl, O.E., Rosencher, N., Kurth, A.A., van Dijk, N.C., Frostick, S.P., Prins, M.H., Hettiarachchi, R., Hantel, S., Schnee, J., Büller, H.R. (2007) Dabigatran etexilate versus enoxaparin for prevention of venous thromboembolism after total hip replacement: A randomised, double-blind, non-inferiority trial. Lancet, 370(9591): 949-56
Eriksson, B.I., Borris, L.C., Friedman, R.J., Haas, S., Huisman, M.V., Kakkar, A.K., Bandel, T.J., Beckmann, H., Muehlhofer, E., Misselwitz, F., Geerts, W. (2008) Rivaroxaban versus enoxaparin for thromboprophylaxis after hip arthroplasty. N Engl J Med, 358(26): 2765-75
Fiessinger, J., Huisman, M.V., Davidson, B.L., Bounameaux, H., Francis, C.W., Eriksson, H., Lundström, T., Berkowitz, S.D., Nyström, P., Thorsén, M., Ginsberg, J.S. (2005) Ximelagatran vs low-molecular-weight heparin and warfarin for the treatment of deep vein thrombosis: A randomized trial. JAMA, 293(6): 681-9
Francis, C.W., Berkowitz, S.D., Comp, P.C., Lieberman, J.R., Ginsberg, J.S., Paiement, G., Peters, G.R., Roth, A.W., McElhattan, J., Colwell, C.W. (2003) Comparison of ximelagatran with warfarin for the prevention of venous thromboembolism after total knee replacement. N Engl J Med, 349(18): 1703-12
Gomez-Outes, A., Suarez-Gea, M.L., Lecumberri, R., Rocha, E., Pozo-Hernandez, C., Vargas-Castrillon, E. (2011) New parenteral anticoagulants in development. Therapeutic Advances in Cardiovascular Disease, 5(1): 33-59
Handin, R. (2004) Krvarenje i tromboza. u: Braunwald E., Fauci A., Kasper D., Hauser S., Longo D., Jameson J., Harrison [ur.] Načela interne medicine, Beograd: Bard-Fin, 354-60
Hirsh, J., O'Donnell, M., Eikelboom, J.W. (2007) Beyond unfractionated heparin and warfarin: Current and future advances. Circulation, 116(5): 552-60
Hirsh, J., Fuster, V., Ansell, J., Halperin, J.L. (2003) American Heart Association/American College of Cardiology Foundation guide to warfarin therapy. Circulation, 107(12): 1692-711
Kakkar, A.K., Brenner, B., Dahl, O.E., Eriksson, B.I., Mouret, P., Muntz, J., Soglian, A.G., Pap, A.F., Misselwitz, F., Haas, S. (2008) Extended duration rivaroxaban versus short-term enoxaparin for the prevention of venous thromboembolism after total hip arthroplasty: A double-blind, randomised controlled trial. Lancet, 372(9632): 31-9
Lassen, M.R., Fisher, W., Mouret, P., Agnelli, G., George, D., Kakkar, A., Mismetti, P., Turpie, A.G.G. (2012) Semuloparin for prevention of venous thromboembolism after major orthopedic surgery: Results from three randomized clinical trials, SAVE-HIP1, SAVE-HIP2 and SAVE-KNEE. Journal of thrombosis and haemostasis, 10(5): 822-32
Lassen, M.R., Ageno, W., Borris, L.C., Lieberman, J.R., Rosencher, N., Bandel, T.J., Misselwitz, F., Turpie, A.G.G. (2008) Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty. N Engl J Med, 358(26): 2776-86
Lassen, M.R., Raskob, G.E., Gallus, A., Pineo, G., Chen, D., Portman, R.J. (2009) Apixaban or Enoxaparin for Thromboprophylaxis after Knee Replacement. New England Journal of Medicine, 361(6): 594-604
Lassen, M.R., Raskob, G.E., Gallus, A., Pineo, G., Chen, D., Hornick, P. (2010) Apixaban versus enoxaparin for thromboprophylaxis after knee replacement (ADVANCE-2): A randomised double-blind trial. Lancet, 375(9717): 807-15
Lassen, M.R., Gallus, A., Raskob, G.E., Pineo, G., Chen, D., Ramirez, L.M. (2010) Apixaban versus Enoxaparin for Thromboprophylaxis after Hip Replacement. New England Journal of Medicine, 363(26): 2487-2498
Lombo, B., Díez, J.G. (2011) Future anticoagulants in interventional cardiology: Anti-IXa and anti-Xa agents in percutaneous coronary intervention. Future cardiology, 7(3): 281-5
Mann, K.G., Butenas, S., Brummel, K. (2003) The dynamics of thrombin formation. Arterioscler Thromb Vasc Biol, 23(1): 17-25
Mannucci, P.M., Franchini, M. (2011) Old and new anticoagulant drugs: A minireview. Annals of medicine, 43(2): 116-23
Marijon, E., Fauchier, L., le Heuzey, J. (2011) New antithrombotic drugs and European approval processes. Lancet, 378(9792): 662-3
Marisavljević, D. (2007) Oralna antikoagulantna terapija - klinički aspekti. Srpski arhiv za celokupno lekarstvo, vol. 135, br. 5-6, str. 352-359
Mavrakanas, T., Bounameaux, H. (2011) The potential role of new oral anticoagulants in the prevention and treatment of thromboembolism. Pharmacology & therapeutics, 130(1): 46-58
Mega, J.L., Braunwald, E., Wiviott, S.D., Bassand, J., Bhatt, D.L., Bode, C., Burton, P., Cohen, M., Cook-Bruns, N., Fox, K.A.A., Goto, S., Murphy, S.A. (2012) Rivaroxaban in patients with a recent acute coronary syndrome. N Engl J Med, 366(1): 9-19
Michael, B., Mück, M., Schwers, W., S. (2012) Effect of Co-Administration of Rivaroxaban and Clopidogrel on Bleeding Time, Pharmacodynamics and Pharmacokinetics: A Phase I Study. Pharmaceuticals, 5(12): 279-296
Misselwitz, F., Berkowitz, S.D., Perzborn, E. (2011) The discovery and development of rivaroxaban. Annals of the New York Academy of Sciences, 1222: 64-75
Oldgren, J., Budaj, A., Granger, C.B., Khder, Y., Roberts, J., Siegbahn, A., Tijssen, J.G.P., van de Werf, F., Wallentin, L. (2011) Dabigatran vs. placebo in patients with acute coronary syndromes on dual antiplatelet therapy: A randomized, double-blind, phase II trial. European heart journal, 32(22): 2781-9
Olsson, B.S. (2003) Stroke prevention with the oral direct thrombin inhibitor ximelagatran compared with warfarin in patients with non-valvular atrial fibrillation (SPORTIF III): Randomised controlled trial. Lancet, 362(9397): 1691-8
Patel, M.R., Mahaffey, K.W., Garg, J., Pan, G., Singer, D.E., Hacke, W., Breithardt, G., Halperin, J.L., Hankey, G.J., Piccini, J.P., Becker, R.C., Nessel, C.C., Paolini, J.F., Berkowitz, S.D. (2011) Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med, 365(10): 883-91
Sabatine, M.S., Antman, E.M., Widimsky, P., Ebrahim, I.O., Kiss, R.G., Saaiman, A., Polasek, R., Contant, C.F., Mccabe, C.H., Braunwald, E. (2009) Otamixaban for the treatment of patients with non-ST-elevation acute coronary syndromes (SEPIA-ACS1 TIMI 42): A randomised, double-blind, active-controlled, phase 2 trial. Lancet, 374(9692): 787-95
Schulman, S., Wahlander, K., Lundstrom, T., Clason, S.B., i dr. (2003) Secondary prevention of venous thromboembolism with the oral direct thrombin inhibitor ximelagatran. N Engl J Med, 349(18): 1713-21
Turpie, A.G.G., Lassen, M.R., Davidson, B.L., Bauer, K.A., Gent, M., Kwong, L.M., Cushner, F.D., Lotke, P.A., Berkowitz, S.D., Bandel, T.J., Benson, A., Misselwitz, F., Fisher, W.D. (2009) Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty (RECORD4): A randomised trial. Lancet, 373(9676): 1673-80
Turpie, A.G.G., Lassen, M.R., Eriksson, B.I., Gent, M., Berkowitz, S.D., Misselwitz, F., Bandel, T.J., Homering, M., Westermeier, T., Kakkar, A.K. (2011) Rivaroxaban for the prevention of venous thromboembolism after hip or knee arthroplasty. Pooled analysis of four studies. Thrombosis and haemostasis, 105(3): 444-53
U.S. Food and drug administration (2011) Pradaxa (dabigatran etexilate mesylate): Drug safety communication - Safety review of post-market reports of serious bleeding events. Silver Spring, http://www.fda.gov/safety/medwatch/safetyinformation/safetyalertsforhumanmedicalproducts/ucm282820.htm
Uchino, K., Hernandez, A.V. (2012) Dabigatran association with higher risk of acute coronary events: Meta-analysis of noninferiority randomized controlled trials. Archives of internal medicine, 172(5): 397-402