New oral antithrombotic strategies

Hot Topics in Cardiology

Volumn , Issue 22, 2011, Pages 7-14

  Ruff, Christian T ^a   Giugliano, Robert P ^a  

^a NONE

Author keywords

[No Author keywords available]

Indexed keywords

ACETYLSALICYLIC ACID; AMIODARONE; ANTICOAGULANT AGENT; ANTIVITAMIN K; APIXABAN; AZD 0837; BETRIXABAN; DABIGATRAN; DAREXABAN; DIGOXIN; EDOXABAN; ENOXAPARIN; KETOCONAZOLE; MACROLIDE; QUINIDINE; RIVAROXABAN; UNCLASSIFIED DRUG; WARFARIN;

ABDOMINAL BLEEDING; ACUTE CORONARY SYNDROME; ARTICLE; BLEEDING; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG HALF LIFE; DRUG MECHANISM; DRUG STRUCTURE; DYSPEPSIA; HEART ATRIUM FIBRILLATION; HUMAN; SIDE EFFECT; STROKE; VENOUS THROMBOEMBOLISM;

EID: 79956326762     PISSN: 19739621     EISSN: 20360924     Source Type: Book Series    
DOI: 10.4147/htc-112207     Document Type: Article

References (66)

1. Fuster V, Ryden LE, Cannom DS, et al. ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (writing committee to revise the 2001 guidelines for the management of patients with atrial fibrillation): Developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. Circulation 2006;114(7):e257-e354.
2. Feinberg W.M, Cornell E.S, Nightingale S.D, et al. Relationship between prothrombin activation fragment F1.2 and international normalized ratio in patients with atrial fibrillation. Stroke prevention in atrial fibrillation investigators. Stroke 1997;28(6):1101-1106.
3. Furberg C.D, Psaty B.M, Manolio T.A, Gardin J.M, Smith V.E, Rautaharju P.M. Prevalence of atrial fibrillation in elderly subjects (the Cardiovascular Health Study). Am J Cardiol 1994;74(3):236-241.
4. Fatkin D, Kelly R.P, Feneley M.P. Relations between left atrial appendage blood flow velocity, spontaneous echocardiographic contrast and thromboembolic risk in vivo. J Am Coll Cardiol 1994;23(4): 961-969.
5. Hwang J.J, Ko F.N, Li Y.H, et al. Clinical implications and factors related to left atrial spontaneous echo contrast in chronic nonvalvular atrial fibrillation. Cardiology 1994;85(2):69-75.
6. Pop G.A, Meeder H.J, Roelandt J.R, et al. Transthoracic echo/ Doppler in the identification of patients with chronic non-valvular atrial ifibrillation at risk for thromboembolic events. Eur Heart J 1994; 15(11):1545-1551.
7. Conway D.S, Pearce L.A, Chin B.S, Hart R.G, Lip G.Y. Plasma von Willebrand factor and soluble P-selectin as indices of endothelial damage and platelet activation in 1321 patients with nonvalvular atrial fibrillation: relationship to stroke risk factors. Circulation 2002; 106(15):1962-1967.
8. Conway D.S, Pearce L.A, Chin B.S, Hart R.G, Lip G.Y. Prognostic value of plasma von Willebrand factor and soluble P-selectin as indices of endothelial damage and platelet activation in 994 patients with nonvalvular atrial fibrillation. Circulation 2003;107(25):3141-3145.
9. Flegel K.M, Shipley M.J, Rose G. Risk of stroke in non-rheumatic atrial fibrillation. Lancet 1987;1(8532):526-529.
10. Wolf P.A, Abbott R.D, Kannel W.B. Atrial fibrillation as an independent risk factor for stroke: The Framingham Study. Stroke 1991;22(8):983-988.
11. Krahn A.D, Manfreda J, Tate R.B, Mathewson FA, Cuddy T.E. The natural history of atrial fibrillation: incidence, risk factors, and prognosis in the Manitoba follow-up study. Am J Med 1995;98(5):476-484.
12. Hart RG, Halperin JL. Atrial fibrillation and thromboembolism: a decade of progress in stroke prevention. Ann Intern Med 1999;131(9): 688-695.
13. Ansell J, Hirsh J, Poller L, Bussey H, Jacobson A, Hylek E. The pharmacology and management of the vitamin K antagonists: The seventh ACCP conference on antithrombotic and thrombolytic therapy. Chest 2004;126(suppl 3):204S-233S.
14. Hart R.G, Pearce L.A, Aguilar M.I. Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med 2007;146(12):857-867.
15. Turpie A.G. New oral anticoagulants in atrial fibrillation. Eur Heart J 2008;29(2):155-165.
16. Mungall D. BIBR-1048 Boehringer Ingelheim. Curr Opin Investig Drugs 2002;3(6):905-907.
17. Weitz J.I, Bates S.M. New anticoagulants. J Thromb Haemost 2005; 3(8):1843-1853.
18. Hauptmann J, Sturzebecher J. Synthetic inhibitors of thrombin and factor Xa: from bench to bedside. Thromb Res 1999;93(5):203-241.
19. Gustafsson D, Elg M. The pharmacodynamics and pharmacokinetics of the oral direct thrombin inhibitor ximelagatran and its active metabolite melagatran: a mini-review. Thromb Res 2003;109(suppl 1):S9-S15.
20. Stangier J, Eriksson B.I, Dahl O.E, et al. Pharmacokinetic profile of the oral direct thrombin inhibitor dabigatran etexilate in healthy volunteers and patients undergoing total hip replacement. J Clin Pharmacol 2005;45(5):555-563.
21. Stangier J, Rathgen K, Stahle H, Gansser D, Roth W. The pharmacokinetics, pharmacodynamics and tolerability of dabigatran etexilate, a new oral direct thrombin inhibitor, in healthy male subjects. Br J Clin Pharmacol 2007;64(3):292-303.
22. Stangier J, Stahle H, Rathgen K, Fuhr R. Pharmacokinetics and pharmacodynamics of the direct oral thrombin inhibitor dabigatran in healthy elderly subjects. Clin Pharmacokinet 2008;47(1):47-59.
23. Stangier J. Clinical pharmacokinetics and pharmacodynamics of the oral direct thrombin inhibitor dabigatran etexilate. Clin Pharmacokinet 2008;47(5):285-295.
24. European Medicines Agency (EMEA). European public assessment report: Pradaxa [online]. Available online at http://www.emea.europa. eu/humandocs/Humans/EPAR/pradaxa/pradaxa.htm
25. Liesenfeld K.H, Schafer H.G, Troconiz I.F, Tillmann C, Eriksson B.I, Stangier J. Effects of the direct thrombin inhibitor dabigatran on ex vivo coagulation time in orthopaedic surgery patients: a population model analysis. Br J Clin Pharmacol 2006;62(5):527-537.
26. Wienen W, Ruehl D, Stassen JM, et al. Effect of recombinant factor VIIa or activated prothrombin complex concentrate on the bleeding time in anaesthetized rats during anticoagulant treatment with the direct thrombin inhibitor dabigatran [Abstract no. P1703]. XXth Congress, International Society of Thrombosis and Haemostasis; 2005 Aug 6-12; Sydney, Australia. Available online from http://www. Blackwellpublishing.com/isth2005/abstract.Asp?id=47211.
27. Eriksson B.I, Dahl O.E, Rosencher N, 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):949-956.
28. Eriksson B.I, Dahl O.E, Rosencher N, et al. Oral dabigatran etexilate vs. subcutaneous enoxaparin for the prevention of venous thromboembolism after total knee replacement: The RE-MODEL randomized trial. J Thromb Haemost 2007;5(11):2178-2185.
29. Ginsberg J.S, Davidson B.L, Comp P.C, et al; RE-MOBILIZE Writing Committee. 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.
30. Ezekowitz M.D, Reilly P.A, Nehmiz G, et al. Dabigatran with or without concomitant aspirin compared with warfarin alone in patients with nonvalvular atrial fibrillation (PETRO study). Am J Cardiol 2007;100(9):1419-1426.
31. Connolly S.J, Ezekowitz M.D, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009;361(12):1139-1151.
32. Eriksson B.I, Quinlan D.J, Weitz J.I. Comparative pharmacodynamics and pharmacokinetics of oral direct thrombin and factor Xa inhibitors in development. Clin Pharmacokinet 2009;48(1):1-22.
33. Roehrig S, Straub A, Pohlmann J, et al. Discovery of the novel antithrombotic agent 5-chloro-N-({(5S)-2-oxo-3- [4-(3-oxomorpholin-4-yl)phenyl]-1,3-oxazolidin-5-yl}methyl)thiophene-2-carboxamide (BAY 59-7939): An oral, direct factor Xa inhibitor. J Med Chem 2005;48(19):5900-5908.
34. Kubitza D, Becka M, Wensing G, Voith B, Zuehlsdorf M. Safety, pharmacodynamics, and pharmacokinetics of BAY 59-7939--an oral, direct factor Xa inhibitor--after multiple dosing in healthy male subjects. Eur J Clin Pharmacol 2005;61(12):873-880.
35. Kubitza D, Becka M, Voith B, Zuehlsdorf M, Wensing G. Safety, pharmacodynamics, and pharmacokinetics of single doses of BAY 59-7939, an oral, direct factor Xa inhibitor. Clin Pharmacol Ther 2005;78(4):412-421.
36. Kubitza D, Becka M, Roth A, Mueck W. Dose-escalation study of the pharmacokinetics and pharmacodynamics of rivaroxaban in healthy elderly subjects. Curr Med Res Opin 2008;24(10):2757-2765.
37. Gross P.L, Weitz J.I. New anticoagulants for treatment of venous thromboembolism. Arterioscler Thromb Vasc Biol 2008;28(3):380-386.
38. Kubitza D, Becka M, Zuehlsdorf M, Mueck W. Effect of food, an antacid, and the H2 antagonist ranitidine on the absorption of BAY 59-7939 (rivaroxaban), an oral, direct factor Xa inhibitor, in healthy subjects. J Clin Pharmacol 2006;46(5):549-558.
39. Kubitza D, Becka M, Mueck W, Zuehlsdorf M. Safety, tolerability, pharmacodynamics, and pharmacokinetics of rivaroxaban--an oral, direct factor Xa inhibitor--are not affected by aspirin. J Clin Pharmacol 2006;46(9):981-990.
40. Kubitza D, Becka M, Zuelsdorf M, Mueck W. No Interaction between the novel, oral direct factor Xa inhibitor BAY 59-7939 and Digoxin. (Abstract 11). J Clin Pharmacol 2006;46:702.
41. Tinel H, Huetter J, Perzborn E. Partial reversal of the anticoagulant effect of high dose rivaroxaban - an oral, direct factor Xa inhibitor - by recombinant factor VIIa in rats [Abstract no. 905]. Blood (ASH Annual Meeting Abstracts) 2006 Nov 16; 108 (11) Available online from http://abstracts.Hematologylibrary.org/content/vol108/issue11.
42. Perzborn E, Harwardt M. Recombinant factor VIIa partially reverses the effects of the factor Xa inhibitor rivaroxaban on thrombin generation, but not the effects of thrombin inhibitors, in vitro [Abstract no. P-W-640]. XXIst Congress, International Society of Thrombosis and Haemostasis; 2007 Jul 6-12; Geneva, Switzerland. Available online from http://www.Blackwellpublishing.com/isth2007/abstract. Asp?id=67890.
43. Eriksson B.I, Borris L.C, Friedman R.J, et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after hip arthroplasty. N Engl J Med 2008;358(26):2765-2775.
44. Kakkar A.K, Brenner B, Dahl O.E, et al. 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(9632):31-39.
45. Lassen M.R, Ageno W, Borris L.C, et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty. N Engl J Med 2008;358(26):2776-2786.
46. Turpie A.G, Lassen M.R, Davidson B.L, et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty (RECORD4): a randomised trial. Lancet 2009;373:1673-1680.
47. Mega J.L, Braunwald E, Mohanavelu S, et al. Rivaroxaban versus placebo in patients with acute coronary syndromes (ATLAS ACS-TIMI 46): A randomised, double-blind, phase II trial. Lancet 2009;374(9683):29-38.
48. U.S. National Institutes of Health. ClinicalTrials.gov. http://www.clinicaltrials.govNCT00494871http://www.clinicaltrials.gov/ct2/show/NCT00494871?term=rivaroxaban&rank=2
49. Gage B.F, Waterman A.D, Shannon W, Boechler M, Rich M.W, Radford M.J. Validation of clinical classification schemes for predicting stroke: results from the national registry of atrial fibrillation. JAMA 2001;285(22):2864-2870.
50. Furugohri T, Isobe K, Honda Y, et al. DU-176b, a potent and orally active factor Xa inhibitor: in vitro and in vivo pharmacological profiles. J Thromb Haemost 2008;6(9):1542-1549.
51. Zafar M.U, Vorchheimer D.A, Gaztanaga J, et al. Antithrombotic effects of factor Xa inhibition with DU-176b: phase-I study of an oral, direct factor Xa inhibitor using an ex-vivo fow chamber. Thromb Haemost 2007;98(4):883-888.
52. Mendell J, Noveck R, Rubets I, Luo R, Shi M, Salazar D. The factor Xa inhibitor edoxaban (DU-176b) is safe in healthy subjects 24 hours post warfarin treatment: a randomized, double-blind study. ISTH Annual Meeting Poster 2009;7(2).
53. Hylek E. DU-176b, an oral, direct factor Xa antagonist. Curr Opin Investig Drugs 2007;8(9):778-783.
54. Weitz J.I, Connolly S.J, Kunitada S, Jin J, Patel I. Randomized, parallel group, multicenter, multinational study evaluating safety of DU-176b compared with warfarin in subjects with non-valvular atrial fibrillation. ASH Annual Meeting Abstracts 2008;112(11):33.
55. Ruff C.T, Giugliano R.P, Antman E.M, et al. Evaluation of the novel factor Xa inhibitor edoxaban compared with warfarin in patients with atrial fibrillation: design and rationale for the Effective aNticoaGulation with factor xA next GEneration in Atrial Fibrillation-Thrombolysis In Myocardial Infarction study 48 (ENGAGE AF-TIMI 48). Am Heart J 2010;160:635-641.
56. Piccini J.P, Patel M.R, Mahaffey K.W, Fox K.A, Califf R.M. Rivaroxaban, an oral direct factor Xa inhibitor. Expert Opin Investig Drugs 2008;17(6):925-937.
57. Raghavan N, Frost CE, Yu Z, et al. Apixaban metabolism and pharmacokinetics after oral administration to humans. Drug Metab Dispos 2009;37(1):74-81.
58. Weitz J.I. Emerging anticoagulants for the treatment of venous thromboembolism. Thromb Haemost 2006;96(3):274-284.
59. Lassen M.R, Raskob G.E, Gallus A, Pineo G, Chen D, Portman R.J. Apixaban or enoxaparin for thromboprophylaxis after knee replacement. N Engl J Med 2009;361(6):594-604.
60. Alexander J.H, Becker R.C, Bhatt D.L, et al; APPRAISE Steering Committee and Investigators. Apixaban, an oral, direct, selective factor Xa inhibitor, in combination with antiplatelet therapy after acute coronary syndrome. results of the apixaban for prevention of acute ischemic and safety events (APPRAISE) trial. Circulation 2009;119(22):2877-2885.
61. U.S. National Institutes of Health. ClinicalTrials.gov.http://www.clinicaltrials.gov NCT00412984http://www.clinicaltrials.gov/ct2/show/NCT00412984?term=apixaba n&rank=9
62. U.S. National Institutes of Health ClinicalTrials.gov.http://www.clinicaltrials.govNCT00684307http://www.clinicaltrials.gov/ct2/show/NCT00684307?term=azd+0837&rank=5
63. U.S. National Institutes of Health. ClinicalTrials.gov. http://www.clinicaltrials.gov NCT00742859http://www.clinicaltrials.gov/ct2/show/NCT00742859?term=betrixaban&rank=1
64. U.S. National Institutes of Health. ClinicalTrials.gov. http://www.clinicaltrials.govNCT00448214http://www.clinicaltrials.gov/ct2/show/NCT00448214?term=YM+150&rank=7
65. Lu G, Luan P, Hollenbach S.J, et al. Reconstructed recombinant factor Xa as an antidote to reverse anticoagulation by factor Xa inhibitors. ISTH Annual Meeting Oral Presentation 2009;7(7).
66. Lu G, DeGuzman F.R, Lakhotia S, Hollenbach S.J, Phillips D.R, Sinha U. Recombinant antidote for reversal of anticoagulation by factor Xa inhibitors. ASH Annual Meeting Abstracts 2008;112(11):983.