Update on pharmacologic approaches to prevent thromboembolism in atrial fibrillation: Are thrombin and factor Xa inhibitors the ultimate answer?

Current Vascular Pharmacology

Volumn 9, Issue 3, 2011, Pages 350-357

  Wolfram, Oliver ^a   Hammwoehner, Matthias ^b   Gramley, Felix ^c   Goette, Andreas ^b  

^a UNIVERSITY HOSPITAL MAGDEBURG   (Germany)

^b St Vinzenz Hospitals GmbH   (Germany)

^c UNIVERSITY MEDICAL CENTER MAINZ   (Germany)

Author keywords

Anticoagulation; Atrial fibrillation; Pathophysiology; Pharmacology; Stroke

Indexed keywords

2 [4 [(1 ACETIMIDOYL 3 PYRROLIDINYL)OXY]PHENYL] 3 (7 AMIDINO 2 NAPHTHYL)PROPIONIC ACID; ACETYLSALICYLIC ACID; ANTICOAGULANT AGENT; ANTIVITAMIN K; APIXABAN; ARGATROBAN; BETRIXABAN; BLOOD CLOTTING FACTOR 10A INHIBITOR; DABIGATRAN; DABIGATRAN ETEXILATE; DAREXABAN; EDOXABAN; ENOXAPARIN; FONDAPARINUX; HEPARIN; HIRULOG; IDRABIOTAPARINUX; IDRAPARINUX; LEPIRUDIN; N [2 [4 (1 METHYL 4 PIPERIDINYL) 1 PIPERAZINYL] 2 OXO 1 PHENYLETHYL] 1H INDOLE 6 CARBOXAMIDE; NEMATODE ANTICOAGULANT PROTEIN 5; NEMATODE ANTICOAGULANT PROTEIN C2; OTAMIXABAN; RAZAXABAN; RECOMBINANT TISSUE FACTOR PATHWAY INHIBITOR; RIVAROXABAN; THROMBIN INHIBITOR; UNCLASSIFIED DRUG; UNINDEXED DRUG; WARFARIN; XIMELAGATRAN; YM 150;

ACUTE CORONARY SYNDROME; AGE; ANTICOAGULANT THERAPY; ARTICLE; BLEEDING; CONGESTIVE HEART FAILURE; DEEP VEIN THROMBOSIS; DIABETES MELLITUS; DOSE RESPONSE; DOUBLE BLIND PROCEDURE; DRUG BLOOD LEVEL; DRUG MECHANISM; DRUG METABOLISM; DRUG WITHDRAWAL; HEART ATRIUM FIBRILLATION; HEART INFARCTION; HUMAN; HYPERTENSION; LIVER TOXICITY; LUNG EMBOLISM; MULTICENTER STUDY (TOPIC); NONHUMAN; PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); RANDOMIZED CONTROLLED TRIAL (TOPIC); RECOMMENDED DRUG DOSE; RISK FACTOR; STROKE; THROMBOEMBOLISM; UNSTABLE ANGINA PECTORIS; VENOUS THROMBOEMBOLISM;

ADMINISTRATION, ORAL; AGE FACTORS; AGED; ANIMALS; ANTICOAGULANTS; ATRIAL FIBRILLATION; FACTOR XA; FIBRINOLYTIC AGENTS; HUMANS; THROMBIN; THROMBOEMBOLISM;

EID: 79955606206     PISSN: 15701611     EISSN: None     Source Type: Journal    
DOI: 10.2174/157016111795495512     Document Type: Article

References (66)

1. Go AS, Hylek EM, Phillips KA, et al. Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study. JAMA 2001; 285: 2370-5.
2. Goette A, Honeycutt C, Langberg JJ. Electrical remodeling in atrial fibrillation. Time course and mechanisms. Circulation 1996; 94: 2968-74.
3. Dobrev D. Electrical remodeling in atrial fibrillation. Herz 2006; 31: 108-12; quiz 42-3.
4. Wolf PA, Dawber TR, Thomas HE, Jr., Kannel WB. Epidemiologic assessment of chronic atrial fibrillation and risk of stroke: the Framingham study. Neurology 1978; 28: 973-7.
5. Hammwohner M, Goette A. Will warfarin soon be passe? New approaches to stroke prevention in atrial fibrillation. J Cardiovasc Pharmacol 2008; 52: 18-27.
6. Wyse DG, Waldo AL, DiMarco JP, et al. A comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med 2002; 347: 1825-33.
7. Blackshear JL, Safford RE. AFFIRM and RACE trials: implications for the management of atrial fibrillation. Card Electrophysiol Rev 2003; 7: 366-9.
8. Hammwohner M, D'Alessandro A, Wolfram O, Goette A. New pharmacologic approaches to prevent thromboembolism in patients with atrial fibrillation. Curr Vasc Pharmacol 2007; 5: 211-9.
9. Di Nisio M, Klerk CP, Meijers JC, Buller HR. The prognostic value of the D-dimer test in cancer patients treated with and without low-molecular-weight heparin. J Thromb Haemost 2005; 3: 1531-3.
10. Weitz JI, Hudoba M, Massel D, Maraganore J, Hirsh J. Clot-bound thrombin is protected from inhibition by heparin-antithrombin III but is susceptible to inactivation by antithrombin III-independent inhibitors. J Clin Invest 1990; 86: 385-91.
11. Weitz JI, Bates SM. New anticoagulants. J Thromb Haemost 2005; 3: 1843-53.
12. Hauel NH, Nar H, Priepke H, Ries U, Stassen JM, Wienen W. Structure-based design of novel potent non-peptide thrombin inhibitors. J Med Chem 2002;45: 1757-66.
13. Hirsh J, O'Donnell M, Eikelboom JW. Beyond unfractionated heparin and warfarin: current and future advances. Circulation 2007; 116: 552-60.
14. Callas DD, Fareed J. Comparative anticoagulant effects of various thrombin inhibitors, as determined in the ecarin clotting time method. Thromb Res 1996; 83: 463-8.
15. 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: 292-303.
16. Eriksson BI, Dahl OE, Ahnfelt L, et al. Dose escalating safety study of a new oral direct thrombin inhibitor, dabigatran etexilate, in patients undergoing total hip replacement: BISTRO I. J Thromb Haemost 2004; 2: 1573-80.
17. Eriksson BI, Dahl OE, Buller HR, et al. A new oral direct thrombin inhibitor, dabigatran etexilate, compared with enoxaparin for prevention of thromboembolic events following total hip or knee replacement: the BISTRO II randomized trial. J Thromb Haemost 2005; 3: 103-11.
18. Eriksson BI, Dahl OE, 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: 2178-85.
19. Eriksson BI, Dahl OE, Rosencher N, et al. Dabigatran etexilate vs. enoxaparin for prevention of venous thromboembolism after total hip replacement: a randomised, double-blind, non-inferiority trial. Lancet 2007; 370: 949-56.
20. Ginsberg JS, Davidson BL, Comp PC, 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: 1-9.
21. Ezekowitz MD, Reilly PA, Nehmiz G, et al. Dabigatran with or without concomitant aspirin compared with warfarin alone in patients with non-valvular atrial fibrillation (PETRO Study). Am J Cardiol 2007; 100: 1419-26.
22. Ezekowitz MD, Connolly S, Parekh A, et al. Rationale and design of RE-LY: randomized evaluation of long-term anticoagulant therapy, warfarin, compared with dabigatran. Am Heart J 2009; 157: 805-10, 10 e1-2.
23. Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran vs. warfarin in patients with atrial fibrillation. N Engl J Med 2009; 361: 1139-51.
24. Hohnloser SH, Connolly SJ. Combined antiplatelet therapy in atrial fibrillation: review of the literature and future avenues. J Cardiovasc Electrophysiol 2003; 14(9 Suppl): S60-3.
25. Markwardt F, Nowak G, Sturzebecher U, Walsmann P. Studies on the pharmacokinetics of hirudin. Biomed Biochim Acta 1987; 46: 237-44.
26. Antman EM, Anbe DT, Armstrong PW, et al. ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1999 Guidelines for the Management of Patients with Acute Myocardial Infarction). Circulation 2004; 110: e82-292.
27. Kleinschmidt S, Stephan B, Pindur G, Bauer C. Argatroban: pharmacological properties and anaesthesiological aspects. Anaesthesist 2006; 55: 443-50.
28. McKeage K, Plosker GL. Argatroban. Drugs 2001; 61: 515-22; discussion 23-4.
29. Walenga JM. An overview of the direct thrombin inhibitor argatroban. Pathophysiol Haemost Thromb 2002; 32 (Suppl 3): 9-14.
30. Yeh RW, Jang IK. Argatroban: update. Am Heart J 2006; 151: 1131-8.
31. Robson R, White H, Aylward P, Frampton C. Bivalirudin pharmacokinetics and pharmacodynamics: effect of renal function, dose, and gender. Clin Pharmacol Ther 2002; 71: 433-9.
32. Buller HR, Destors J-M, Gallus AS, Prins MH, Raskob GE. Idrabiotaparinux, a biotinylated long-acting anticoagulant, in the treatment of deep venous thrombosis (EQUINOX Study): safety, efficacy, and reversibility by avidin. ASH Annual Meeting Abstracts 2008; 112: 32.
33. Eriksson BI, Borris LC, Friedman RJ, et al. Rivaroxaban vs. enoxaparin for thromboprophylaxis after hip arthroplasty. N Engl J Med 2008; 358: 2765-75.
34. Lassen MR, Ageno W, Borris LC, et al. Rivaroxaban vs. enoxaparin for thromboprophylaxis after total knee arthroplasty. N Engl J Med 2008; 358: 2776-86.
35. Turpie AG, Lassen MR, Davidson BL, et al. Rivaroxaban vs. enoxaparin for thromboprophylaxis after total knee arthroplasty (RECORD4): a randomised trial. Lancet 2009; 373: 1673-80.
36. Buller HR, Lensing AW, Prins MH, et al. A dose-ranging study evaluating once-daily oral administration of the factor Xa inhibitor rivaroxaban in the treatment of patients with acute symptomatic deep vein thrombosis: the Einstein-DVT Dose-Ranging Study. Blood 2008; 112: 2242-7.
37. Walenga JM, Prechel M, Jeske WP, et al. Rivaroxaban--an oral, direct Factor Xa inhibitor--has potential for the management of patients with heparin-induced thrombocytopenia. Br J Haematol 2008; 143: 92-9.
38. Turpie AG. New oral anticoagulants in atrial fibrillation. Eur Heart J 2008; 29: 155-65.
39. Haas S. New oral Xa and IIa inhibitors: updates on clinical trial results. J Thromb Thrombolysis 2008; 25: 52-60.
40. Weitz JI. Emerging anticoagulants for the treatment of venous thromboembolism. Thromb Haemost 2006; 96: 274-84.
41. Lassen MR, Raskob GE, Gallus A, Pineo G, Chen D, Portman RJ. Apixaban or enoxaparin for thromboprophylaxis after knee replacement. N Engl J Med 2009; 361: 594-604.
42. Fujii Y, Takahashi M, Morita H, Kikuchi H, Aramaki Y, Amidon GL. Characteristics of gastrointestinal absorption of DX-9065a, a new synthetic anticoagulant. Drug Metab Pharmacokinet 2007; 22: 26-32.
43. Alexander JH, Yang H, Becker RC, et al. First experience with direct, selective factor Xa inhibition in patients with non-STelevation acute coronary syndromes: results of the XaNADU-ACS Trial. J Thromb Haemost 2005; 3: 439-47.
44. Paccaly A, Frick A, Rohatagi S, et al. Pharmacokinetics of otamixaban, a direct factor Xa inhibitor, in healthy male subjects: pharmacokinetic model development for phase 2/3 simulation of exposure. J Clin Pharmacol 2006; 46: 37-44.
45. Cohen M, Bhatt DL, Alexander JH, et al. Randomized, doubleblind, dose-ranging study of otamixaban, a novel, parenteral, shortacting direct factor Xa inhibitor, in percutaneous coronary intervention: the SEPIA-PCI trial. Circulation 2007; 115: 2642-51.
46. Turpie AG, Bauer KA, Davidson BL, et al. A randomized evaluation of betrixaban, an oral factor Xa inhibitor, for prevention of thromboembolic events after total knee replacement (EXPERT). Thromb Haemost 2009; 101: 68-76.
47. Agnelli G, Haas S, Ginsberg JS, Krueger KA, Dmitrienko A, Brandt JT. A phase II study of the oral factor Xa inhibitor LY517717 for the prevention of venous thromboembolism after hip or knee replacement. J Thromb Haemost 2007; 5: 746-53.
48. Zafar MU, Vorchheimer DA, 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 flow chamber. Thromb Haemost 2007; 98: 883-8.
49. Fuji T, Fujita S, Tachibana S, Kawai Y. Randomized, double-blind, multi-dose efficacy, safety and biomarker study of the oral factor Xa inhibitor DU-176b compared with placebo for prevention of venous thromboembolism in patients after total knee arthroplasty Blood 2008; 112: 34 (Abstract).
50. Raskob G, Cohen A, Eriksson B, et al. Randomized double-blind multi-dose trial of the oral factor-Xa inhibitor DU-176b vs. LMW Heparin (Dalteparin) for prevention of venous thromboembolism after total hip replacement. Eur Heart J 2008; 29: 609 (Abstract).
51. Weitz JI, Connolly SJ, 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. Blood 2008; 112: 33 (Abstract).
52. Iwatsuki Y, Shigenaga T, Moritani Y, et al. Biochemical and pharmacological profiles of YM150, an oral direct factor Xa inhibitor. Blood 2006; 108: 911 (Abstract).
53. Turpie AGG. Oral, direct factor Xa inhibitors in development for the prevention and treatment of thromboembolic diseases. Arterioscler Thromb Vasc Biol 2007; 27: 1238-47.
54. Rios-Steiner JL, Murakami MT, Tulinsky A, Arni RK. Active and exo-site inhibition of human factor Xa: structure of des-Gla factor Xa inhibited by NAP5, a potent nematode anticoagulant protein from Ancylostoma caninum. J Mol Biol 2007; 371: 774-86.
55. Lee A, Agnelli G, Buller H, et al. Dose-response study of recombinant factor VIIa/tissue factor inhibitor recombinant nematode anticoagulant protein c2 in prevention of postoperative venous thromboembolism in patients undergoing total knee replacement. Circulation 2001; 104: 74-8.
56. Moons AH, Peters RJ, Bijsterveld NR, et al. Recombinant nematode anticoagulant protein c2, an inhibitor of the tissue factor/factor VIIa complex, in patients undergoing elective coronary angioplasty. J Am Coll Cardiol 2003; 41: 2147-53.
57. Giugliano RP, Wiviott SD, Stone PH, et al. Recombinant nematode anticoagulant protein c2 in patients with non-ST-segment elevation acute coronary syndrome: the ANTHEM-TIMI-32 trial. J Am Coll Cardiol 2007; 49: 2398-407.
58. Presta L, Sims P, Meng YG, et al. Generation of a humanized, high affinity anti-tissue factor antibody for use as a novel antithrombotic therapeutic. Thromb Haemost 2001; 85: 379-89.
59. Vincent JL, Artigas A, Petersen LC, Meyer C. A multicenter, randomized, double-blind, placebo-controlled, dose-escalation trial assessing safety and efficacy of active site inactivated recombinant factor VIIa in subjects with acute lung injury or acute respiratory distress syndrome. Crit Care Med 2009; 37: 1874-80.
60. Abraham E, Reinhart K, Opal S, et al. Efficacy and safety of tifacogin (recombinant tissue factor pathway inhibitor) in severe sepsis: a randomized controlled trial. JAMA 2003; 290: 238-47.
61. Lassen M, Davidson BL, Gallus A, et al. A phase II randomized, double-blind, five-arm, parallel-group, dose-response study of a new oral directly acting factor Xa inhibitor, razaxaban, for the prevention of deep vein thrombosis in knee replacement surgery-on behalf of the Razaxaban investigators (abstract). Blood 2003; 102: 15a.
62. Eriksson BI, Dahl OE, Lassen MR, et al. Partial factor IXa inhibition with TTP889 for prevention of venous thromboembolism: an exploratory study. J Thromb Haemost 2008; 6: 457-63.
63. Gomez-Outes A, Lecumberri R, Pozo C, Rocha E. New anticoagulants: focus on venous thromboembolism. Curr Vasc Pharmacol 2009; 7: 309-29.
64. Lassen MR, Dahl OE, Mismetti P, Destree D, Turpie AG. AVE5026, a new hemisynthetic ultra-low-molecular-weight heparin for the prevention of venous thromboembolism in patients after total knee replacement surgery--TREK: a dose-ranging study. J Thromb Haemost 2009; 7: 566-72.
65. Kearon C, Comp P, Douketis J, Royds R, Yamada K, Gent M. Dose-response study of recombinant human soluble thrombomodulin (ART-123) in the prevention of venous thromboembolism after total hip replacement. J Thromb Haemost 2005; 3: 962-8.
66. Saito H, Maruyama I, Shimazaki S, et al. Efficacy and safety of recombinant human soluble thrombomodulin (ART-123) in disseminated intravascular coagulation: results of a phase III, randomized, double-blind clinical trial. J Thromb Haemost 2007; 5: 31-41.