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Rivaroxaban and factor Xa inhibitors in clinical practice


Authors: M. Penka
Authors‘ workplace: Oddělení klinické hematologie FN Brno, pracoviště Bohunice, přednosta prof. MU Dr. Miroslav Penka, CSc.
Published in: Vnitř Lék 2010; 56(9): 920-926
Category: Reviews

Overview

Prevention and treatment of thrombosis represent some of the most common medical interventions in the clinical area that remains among the most common causes of mortality and morbidity. At present, heparins, pentasaccharides and warfarin are used to prevent thromboembolic events. Nevertheless, these drugs have a range of adverse effects and other disadvantages that force scientists to seek new treatment options that would fulfil the concept of an ‘ideal antithrombotic drug’. Characteristics of such an agent include selectivity of its effect, absence of adverse effects, possibility to administer the drug without the need for laboratory control and low cost. Attention is, therefore, focused on thrombin modulation either with direct inhibitors or with inhibitors of the thrombin production system, i.e. activated factor Xa of the plasma coagulation cascade (F Xa). Management so far involved injectable formulations, the efforts described above aim for oral administration of treatment.

Key words:
coagulation –  thrombosis –  antithrombotics –  Xa inhibitors –  rivaroxaban


Sources

1. Geerts W. Factor Xa inhibitors. Hematology 2004, American Society of Hematology Education Program Book: 428– 431.

2. Hirsh J, O’Donnell M, Weitz JI. New anticoagulants. Blood 2005; 105: 453– 463.

3. Weitz JI, Hirsh J. New antithrombotic drugs. In: Colman RW, Hirsh J, Marder VJ et al (eds). Hemostasis and thrombosis. Philadelphia: Lippincott Williams & Wilkins 2001: 1529– 1544.

4. Turpie AG. Pentasaccharides. Semin Hematol 2002; 39: 158– 171.

5. Moll S, Roberts HR. Overview of anticoagulant drugs for the future. Semin Hematol 2002; 39: 145– 157.

6. Bultas J, Karetová D. Nové trendy farmakoterapie kardiovaskulárních chorob. Vnitř Lék 2004; 50 (Suppl 1): S37– S58.

7. Weitz JI, Hirsch J, Samama MM. New anticoagulant drugs: the seventh ACCP conference on antithrombotic and thrombolytic therapy. Chest 2004; 126 (Suppl 3): 265S– 286S.

8. Turpie AG. Oral, direct factor Xa inhibitors in development for the prevention and treatment of thrombembolic diseases. Arterioscler Thromb Vasc Biol 2007; 27: 1238– 1247.

9. Kubitza D, Haas S. Novel factor Xa inhibitors for prevention and treatment of thrombembolic diseases. Expert Opin Investig Drugs 2006; 15: 843– 855.

10. Piccini JP, Patel MR, Mahaffey KW et al. Rivaroxaban, an oral direct factor Xa inhibitor. Expert Opin Investig Drugs 2008; 17: 925– 937.

11. Turpie AG, Fischer WD, Bauer KA et al. ODIXa‑ Knee Study Group. BAY 59- 7939: An oral, direct factor Xa inhibitor for the prevention of venous thrombembolism in patients after total knee replacement. A phase I dose‑ranging study. J Tromb Haemost 2005; 3: 2479– 2486.

12. Agnelli G, Gallus A, Goldhaber S et al. Treatment of acute, symptomatic, proximal deep vein thrombosis with the oral, direct factor Xa inhibitor rivaroxaban (BAY 59- 7939) –  The ODIXa‑ DVT dose‑ranging study. World Congress Cardiology 2006. Abstract P4569.

13. Eriksson BI, Borris LC, Friedman RJ et al. RECORD1 Study Group. Rivaroxaban versus enoxaparin for thromboprophylaxis after hip arthroplasty. N Engl J Med 2008; 358: 2765– 2775.

14. Kakkar AK, Brenner B, Dahl OE et al. RECORD2 Investigators. Extended duration rivaroxaban versus short‑term enoxaparin for the prevention of venous thromboembolism after total hip arthroplasty: a double‑blind, randomised controlled trial. Lancet 2008; 372: 31– 39.

15. Lassen MR, Ageno W, Borris LC et al. RECORD3 Investigators. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty. N Engl J Med 2008; 358: 2776– 2736.

16. Turpie AG, Bauer KA, Berkowitz SD et al. RECORD4 Investigators. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty (RECORD4): a randomised trial. Lancet 2009; 373: 1673– 1680.

17. Tinel H, Huetter J, Perzborn E. Recombinant factor VIIa partially reverses the anticoagulant effect of high‑dose rivaroxaban –  a novel, oral Factor Xa inhibitor –  in rats. J Thromb Haemost 2007; 5 (Suppl 2): Abstract P‑ W‑ 652.

18. Perzborn E, Tinel H. FEIBA reverses the effect of a high dose of rivaroxaban in rats. Pathophysiol Haemost Thromb 2008; 36: A40.

19. Buller HR. Once daily treatment with an oral, direct factor Xa inhibitor –  rivaroxaban (BAY 59- 7939) –  in patients with acute symptomatic deep vein thrombosis. The EINSTEIN- DVT dose‑finding study. World Congress Cardiology 2006. Abstract P4568.

20. Buller HR. Once- daily oral rivaroxaban versus placebo in the long‑term prevention of recurrent symptomatic venous thromboembolism. The Einstein‑Extension Study. Blood 2009; 114: Abstract No LBA– 2.

21. Haas S. Rivaroxaban –  an oral, direct Factor Xa inhibitor –  lessons from a broad clinical study programme. Eur J Haematol 2009; 82: 339– 349.

22. Gibson CM, Mega JL, Hammett CJ et al. Randomized comparison of rivaroxaban, an oral direct factor Xa inhibitor, with placebo in patients with acute coronary syndromes: the ATLAS ACS- TIMI 46 trial. Circulation 2008; 118: 2311.

23. Kvasnička J. Nová perorální an­ti­trom­botika –  poznámky pro praxi. ČSTH 2009.

24. Fischer WD, Ericsson BI, Bauer KA et al. Rivaroxaban for thromboprophylaxis after orthopedic surgery: Pooled analysis of two studies. Blood Coagulation, Fibrinolysis and Cellular Haemostasis. Thromb Haemost 2007; 97: 931– 937.

25. Abendschein DR, Baum PK, Martin DJ et al. Effects of ZK- 807834, a novel inhibitor of factor Xa, on arterial and venous thrombosis in rabbits. J Cardiovasc Pharmacol 2000; 35: 796– 805.

26. Rebello SS, Kasiewski CJ, Wang W et al. Role of short‑term inhibition of factor Xa by FX673 in arterial passivation: A study in a chronic model of thrombosis in conscious dogs. J Cardiovasc Pharmacol 2001; 38: 288– 297.

27. Bostwick JS, Bentley R, Morgan S et al. RPR120844, a novel, specific inhibitor of coagulation factor Xa inhibits venous thrombosis in the rabbit. Thromb Haemost 1999; 81: 157– 160.

28. Asakura H, Ontachi Y, Mizutani T et al. Beneficial effect of JTV- 803, a new synthetic inhibitor of activated factor X, against both lipopolysaccharide‑induced and tissue factor‑induced disseminated intravascular coagulation in rat models. Blood Coagul Fibrinolysis 2002; 13: 233– 239.

29. Chi L, Peng YW, Gipson G et al. In vitro and in vivo antithrombotic activity of PD- 19891, a novel synthetic factor Xa inhibitor. J Cardiovasc Pharmacol 2004; 44: 493– 500.

30. Wong PC, Pinto DJ, Knabb RM. Effects of recombinant factor VIIa on the antithrombotic and bleeding time effects of SS457, a direct factor Xa inhibitor, in rats. Arterioscler Thromb BASF Biol 2004; 24: E– 66.

31. Fareed J, Hoppensteadt DA, Bick RL. Management of thrombotic and cardiovascular disorders in the new millennium. Clin Appl Thromb Hemost 2003; 9: 101– 108.

32. Robinson DM, Wellington K. Fondaparinus sodium: a review of its use in the treatment of acute venous thromboembolism. Am J Cardovasc Drugs 2005; 5: 335– 346.

33. Hyers TM. Management of venous thromboembolism: past, present and future. Arch Intern Med 2003; 163: 759– 768.

34. Mehta SR, Yusuf S, Granger CB et al. MICHELANGELO OASIS 5 Steering Committee. Design and rationale of the MICHELANGELO Organization to assess strategies in acute ischemic syndromes (OASIS)- 5 trial program evaluating fondaparinux, a synthetic factor Xa inhibitor, in patients with non‑ST‑segment elevation acute coronary syndromes. Am Heart J 2005; 150: 1107.

35. Savi P, Chong BH, Greinacher A et al. Effect of fondaparinux on platelet activation in presence of heparin‑dependent antibodies: a blinded comparative multicentre study with unfractionated heparin. Blood 2005; 105: 139– 144.

36. Tobu M, Iqbal O, Messmore HL et al. Influence of different anticoagulant agents on fibrinopeptide a generation. Clin Appl Thromb Hemost 2003; 9: 273– 292.

37. PERSIST Investigators. A novel long‑-acting synthetic factor Xa inhibitor (SanOrg34006) to replace warfarin for secondary prevention in deep vein thrombosis: a phase II evaluation. J Thromb Haemost 2004; 2: 47– 53.

38. Penka M, Buliková A, Matýšková M. Nová an­ti­trom­botika. Postgrad Med 2009; 11: 124– 132.

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