Direct thrombin inhibitors

Journal of Cardiovascular Pharmacology and Therapeutics

Volumn 17, Issue 1, 2012, Pages 5-11

  O'Brien, P Joshua ^a   Mureebe, Leila ^a  

^a DUKE UNIVERSITY MEDICAL CENTER   (United States)

Author keywords

pathophysiology; thrombosis

Indexed keywords

AMIODARONE; ARGATROBAN; AZD 0837; BLOOD CLOTTING FACTOR 7; DABIGATRAN; DABIGATRAN ETEXILATE; DESULFATOHIRUDIN; ENOXAPARIN; FIBRINOGEN RECEPTOR ANTAGONIST; FONDAPARINUX; GLYCOPROTEIN IB; HEPARIN; HIRUDIN; HIRUDIN DERIVATIVE; HIRULOG; LEPIRUDIN; LOW MOLECULAR WEIGHT HEPARIN; MACROGOL; PEGMUSIRUDIN; QUINIDINE; RIVAROXABAN; STREPTOKINASE; THROMBIN; THROMBIN INHIBITOR; THROMBOPLASTIN; UNCLASSIFIED DRUG; VERAPAMIL; VON WILLEBRAND FACTOR; WARFARIN; XIMELAGATRAN;

ACUTE CORONARY SYNDROME; ACUTE HEART INFARCTION; ALANINE AMINOTRANSFERASE BLOOD LEVEL; ARTERY THROMBOSIS; BLEEDING; CLINICAL TRIAL (TOPIC); DRUG DOSE COMPARISON; DRUG DOSE REDUCTION; DRUG HYPERSENSITIVITY; DRUG WITHDRAWAL; DYSPEPSIA; FOOD; FOOD DRUG INTERACTION; HEART ATRIUM FIBRILLATION; HEART INFARCTION; HEPARIN INDUCED THROMBOCYTOPENIA; HUMAN; LIVER DISEASE; LIVER FAILURE; META ANALYSIS (TOPIC); ORTHOPEDIC SURGERY; PERCUTANEOUS CORONARY INTERVENTION; PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); POSTOPERATIVE COMPLICATION; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SIDE EFFECT; ST SEGMENT ELEVATION; STENOSIS; STROKE; THROMBOCYTE; THROMBOSIS; VENOUS THROMBOEMBOLISM;

ANIMALS; ANTITHROMBINS; BLOOD COAGULATION; CARDIOVASCULAR DISEASES; CLINICAL TRIALS AS TOPIC; HUMANS; THROMBOSIS;

EID: 84856951063     PISSN: 10742484     EISSN: 19404034     Source Type: Journal    
DOI: 10.1177/1074248410395941     Document Type: Review

References (74)

1. "Leading causes of death in males/females, United States, 2004". http://www.cdc.gov. Accessed October 23, 2009.
2. Makin A, Silverman SH, Lip GY.. Peripheral vascular disease and Virchow's triad for thrombogenesis. QJM. 2002 ; 95 (4). 199-210 (Pubitemid 34413726)
3. Oldenburg J, Schwaab R.. Molecular biology of blood coagulation. Semin Thromb Hemost. 2001 ; 27 (4). 313-324 (Pubitemid 32802888)
4. Hickey MJ, Williams SA, Roth GJ.. Human platelet glycoprotein IX: an adhesive prototype of leucine rich glycoproteins with flank-center-flank structures. Proc Natl Acad Sci USA. 1989 ; 86 (17). 6773-6777
5. Bevers EM, Rosing J, Zwaal RFA Mechanisms of Stimulus Response Coupling in Platelets. Westweek J Scully MF McIntyre DE Kakkar VV, ed. New York, NY: Plenum Press ; 1986: 359-372.
6. Edgington TS, Mackman N, Brand K, Ruf W.. The structural biology of the expression and function of tissue factor. Thromb Haemost. 1991 ; 66 (1). 67
7. Furie B, Furie BC.. Mechanisms of Thrombus Formation. New Engl J Med. 2008 ; 359 (9). 938-949
8. Hassouna HI.. Laboratory evaluation of hemostatic disorders. Hematol Oncol Clin North Am. 1993 ; 7 (6). 1161-1249
9. Samama MM.. The mechanism of action of rivaroxaban-an oral, direct Factor Xa inhibitor-compared with other anticoagulants. Thromb Res. 2011 ; 127 (6). 497-504
10. Vandy FC, Wakefield TW. Comprehensive Vascular and Endovascular Surgery. 2 nd ed. Philadelphia, PA: Elsevier; 2009:21-38. Hallett J Mills J Earnshaw J Reekers J Rooke T, ed. Philadelphia, PA: Elsevier ; 2009: 21-38.
11. Davie EW, Fujikawa K, Kisiel W.. The coagulation cascade: initiation, maintenance, and regulation. Biochemistry. 1991 ; 30 (43). 10363-10370
12. Hommes DW, Bura A, Mazzolai L, Buller HR, ten Cate JW.. Subcutaneous heparin compared with continuous intravenous heparin administration in the initial treatment of deep vein thrombosis: a meta-analysis. Ann Intern Med. 1992 ; 116 (4). 279-284
13. Weitz JI, Crowther M.. Direct thrombin inhibitors. Thromb Res. 2002 ; 106 (3). V275 - V284
14. Bates SM, Weitz JI.. Direct thrombin inhibitors for treatment of arterial thrombosis: potential differences between bivalirudin and hirudin. Am J Cardiol. 1998 ; 82 (8). 12-18
15. Greinacher A, Potzsch B, Amiral J, Dummel V, Eichner A, Mueller-Eckhardt C.. Heparin-associated thrombocytopenia: isolation of the antibody and characterization of a multimolecular PF4-heparin complex as the major antigen. Thromb Haemost. 1994 ; 71 (2). 247-251 (Pubitemid 24047336)
16. Warkentin TE, Maurer BT, Aster RH.. Heparin-induced thrombocytopenia associated with fondaparinux. N Engl J Med. 2007 ; 356 (25). 2653-2655
17. 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 (1). 92-99
18. Herbert JM, Herault JP, Bernat A, et al. Biochemical and pharmacological properties of SANORG 34006, a potent and long-acting synthetic pentasaccharide. Blood. 1998 ; 91 (11). 4197-4205 (Pubitemid 28261983)
19. Meissner M Vascular Surgery. 6 th ed. Philadelphia, PA: Elsevier; 2005:511-529. Rutherford R, ed. Philadelphia, PA: Elsevier ; 2005: 511-529.
20. Shapiro SS.. Treating thrombosis in the 21st century. N Engl J Med. 2003 ; 349 (18). 1762
21. Di Nisio M, Middeldorp S, Buller HR.. Direct thrombin inhibitors. N Engl J Med. 2005 ; 353 (10). 1028-1041
22. Rydel TJ, Ravichandran KG, Tulinsky A, et al. The structure of a complex of recombinant hirudin and human -thrombin. Science. 1990 ; 249 (4966). 277-280
23. Direct thrombin inhibitors in acute coronary syndromes: principal results of a meta-analysis based on individual patients' data. Lancet. 2002 ; 359 (9309). 294-302
24. Lubenow N, Eichler P, Lietz T, Farner B, Greinacher A.. Lepirudin for prophylaxis of thrombosis in patients with acute isolated heparin-induced thrombocytopenia: an analysis of 3 prospective studies. Blood. 2004 ; 104 (10). 3072-3077 (Pubitemid 39507121)
25. Hacquard M, de Maistre E, Lecompte T.. Lepirudin: is the approved dosing schedule too high?. J Thromb Haemost. 2005 ; 3 (11). 2593-2596 (Pubitemid 41727183)
26. Crowther MA, Warkentin TE.. Bleeding risk and the management of bleeding complications in patients undergoing anticoagulant therapy: focus on new anticoagulant agents. Blood. 2008 ; 111 (10). 4871-4879
27. Greinacher A, Lubenow N, Eichler P.. Anaphylactic and anaphylactoid reactions associated with lepirudin in patients with heparin-induced thrombocytopenia. Circulation. 2003 ; 108 (17). 2062-2065 (Pubitemid 37337579)
28. Eriksson BI, Wille-Jorgensen P, Kalebo P, et al. A comparison of recombinant hirudin with a low-molecular-weight heparin to prevent thromboembolic complications after total hip replacement. N Engl J Med. 1997 ; 337 (19). 1329-1335 (Pubitemid 27467766)
29. Eriksson BI, Ekman S, Lindbratt S, et al. Prevention of thromboembolism with use of recombinant hirudin: results of a double-blind, multicenter trial comparing the efficacy of desirudin (Revasc) with that of unfractionated heparin in patients having a total hip replacement. J Bone Joint Surg Am. 1997 ; 79 (3). 326-333 (Pubitemid 27136640)
30. http://www.clinicaltrial.gov/ct2/results?term=desirudin. Accessed Oct 27, 2009.
31. Hesslinger HU, Haas S, Maurer R, et al. Pharmacodynamic and safety results of PEG-hirudin in healthy volunteers. Thromb Haemost. 1997 ; 77 (5). 1006-1012
32. Bossavy JP, Sakariassen KS, Rubsamen K, et al. Comparison of the antithrombotic effect of PEG-Hirudin and Heparin in a human ex vivo model of arterial thrombosis. Arterioscler Thromb Vasc Biol. 1999 ; 19 (5). 1348-53 (Pubitemid 29227657)
33. http://www.clinicaltrials.gov/ct2/results?intr=%22PEG-hirudin%22. Accessed November 2, 2009.
34. Maraganore JM, Bourdon P, Jablonski J, Ramachandran KL, Fenton JW. Design and characterization of hirulogs: a novel class of bivalent peptide inhibitors of thrombin. Biochemistry. 1990 ; 29 (30). 7095-7101 (Pubitemid 20241158)
35. Parry MA, Maraganore JM, Stone SR.. Kinetic mechanism for the interaction of Hirulog with thrombin. Biochemistry. 1994 ; 33 (49). 14807-14814
36. White H. Thrombin-specific anticoagulation with bivalirudin versus heparin in patients receiving fibrinolytic therapy for acute myocardial infarction: the HERO-2 randomised trial. Lancet. 2001 ; 358 (9296). 1855-1863 (Pubitemid 34008652)
37. Lincoff AM, Bittl JA, Harrington RA, et al. REPLACE-2 Investigators. Bivalirudin and provisional glycoprotein IIb/IIIa blockade compared with heparin and planned glycoprotein IIb/IIIa blockade during percutaneous coronary intervention: REPLACE-2 randomized trial. JAMA. 2003 ; 289 (7). 853-863 (Pubitemid 37430344)
38. Stone GW, McLaurin BT, Cox DA, et al. ACUITY investigators. Bivalirudin for patients with acute coronary syndromes. N Engl J Med. 2006 ; 355 (21). 2203-2216 (Pubitemid 44791162)
39. Stone GW, Witzenbichler B, Guagliumi G, et al. HORIZONS-AMI Trial investigators. Bivalirudin during Primary PCI in Acute Myocardial Infarction. N Engl J Med. 2008 ; 358 (21). 2218-2230 (Pubitemid 351724451)
40. http://www.clinicaltrials.gov/ct2/results?term=bivalirudin. Accessed November 2, 2009.
41. Berry CN, Girardot C, Lecoffre C, Lunven C.. Effects of the synthetic thrombin inhibitor argatroban on fibrin- or clot-incorporated thrombin: comparison with heparin and recombinant hirudin. Thromb Haemost. 1994 ; 72 (3). 381-386 (Pubitemid 24280776)
42. Lewis BE, Wallis DE, Berkowitz SD, et al. ARG-911 Study Investigators. Argatroban anticoagulant therapy in patients with heparin-induced thrombocytopenia. Circulation. 2001 ; 103 (14). 1838-1843 (Pubitemid 32328395)
43. Lewis BE, Wallis DE, Leya F, Hursting MJ, Kelton JG.. Argatroban-915 Investigators. Argatroban anticoagulation in patients with heparin-induced thrombocytopenia. Arch Intern Med. 2003 ; 163 (15). 1849-1856 (Pubitemid 36960936)
44. Olsson SB.. Executive Steering Committee of the SPORTIF III Investigators. Stroke prevention with the oral direct thrombin inhibitor ximelagatran compared with warfarin in patients with non-valvular atrial fibrillation (SPORTIF III): randomized controlled trial. Lancet. 2003 ; 362 (9397). 1691-1698 (Pubitemid 37468318)
45. Albers GW, Diener HC, Frison L, et al. SPORTIF Executive Steering Committee for the SPORTIF V Investigators. Ximelagatran vs warfarin for stroke prevention in patients with nonvalvular atrial fibrillation: a randomized trial. JAMA. 2005 ; 293 (6). 690-698
46. Wallentin L, Wilcox RG, Weaver WD, et al. ESTEEM Investigators. Oral ximelagatran for secondary prophylaxis after myocardial infarction: the ESTEEM randomized controlled trial. Lancet. 2003 ; 362 (9386). 1691-1698
47. Colwell CW, Berkowitz SD, Davidson BL, et al. Comparison of ximelagatran, an oral direct thrombin inhibitor, with enoxaparin for the prevention of venous thromboembolism following total hip replacement: a randomized, double-blind study. J Thromb Haemost. 2003 ; 1 (10). 2119-2130
48. Francis CW, Davidson BL, Berkowitz SD, et al. Ximelagatran versus warfarin for the prevention of venous thromboembolism after total knee arthroplasty: a randomized, double-blind trial. Ann Intern Med. 2002 ; 137 (8). 648-655 (Pubitemid 35176097)
49. Francis CW, Berkowitz SD, Comp PC, et al. Comparison of ximelagatran with warfarin for the prevention of venous thromboembolism after total knee replacement. N Engl J Med. 2003 ; 349 (5). 1703-1712 (Pubitemid 37315007)
50. Eriksson BI, Agnelli G, Cohen AT, et al. METHRO III Study Group. Direct thrombin inhibitor melagatran followed by oral ximelagatran in comparison with enoxaparin for prevention of venous thromboembolism after total hip or knee replacement. Thromb Haemost. 2003 ; 89 (2). 288-296 (Pubitemid 36227281)
51. Eriksson BI, Agnelli G, Cohen AT, et al. EXPRESS Study Group. The direct thrombin inhibitor melagatran followed by oral ximelagatran compared with enoxaparin for the prevention of venous thromboembolism after total hip or knee replacement: the EXPRESS study. J Thromb Haemost. 2003 ; 1 (12). 2490-2496
52. Fiessinger JN, Huisman MV, Davidson BL, et al. THRIVE Treatment Study Investigators. Ximelagatran vs low-molecular-weight heparin and warfarin for the treatment of deep vein thrombosis: a randomized trial. JAMA. 2005 ; 293 (6). 681-689 (Pubitemid 40216038)
53. Schulman S, Wahlander K, Lundstrom T, Clason SB, Eriksson H.. THRIVE III Investigators. Secondary prevention of venous thromboembolism with the oral direct thrombin inhibitor ximelagatran. N Engl J Med. 2003 ; 249 (18). 1713-1721 (Pubitemid 37315008)
54. Mohapatra R, Tran M, Gore JM, Spencer FA.. A review of the oral direct thrombin inhibitor ximelagatran: not yet the end of the warfarin era. Am Heart J. 2005 ; 150 (1). 19-26 (Pubitemid 41097425)
55. Baetz BE, Spinler SA.. Dabigatran etexilate: an oral direct thrombin inhibitor for prophylaxis and treatment of thromboembolic diseases. Pharmacotherapy. 2008 ; 28 (11). 1354-1373
56. Lip GYH, et al. The oral direct thrombin inhibitor AZD0837 for the prevention of stroke and systemic embolism in patients with atrial fibrillation: a phase II randomized dose-guiding, safety, and tolerability study. Abstract 1021 presented at the 58th Annual Scientific Sessions of the American College of Cardiology (ACC) ; 2009 Orlando, Florida ; 2009..
57. Squizzato A, Dentali F, Steidl L, Ageno W.. New direct thrombin inhibitors. Intern Emerg Med. 2009 ; 4 (6). 479-484
58. Troconiz IF, Tillmann C, Liesenfeld KH, Schafer HG, Stangier J.. Population pharmacokinetic analysis of the new oral thrombin inhibitor dabigatran etexilate (BIBR 148) in patients undergoing primary elective total hip replacement surgery. J Clin Pharmacol. 2007 ; 47 (3). 371-382 (Pubitemid 46294714)
59. 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 (1). 103-111 (Pubitemid 41647122)
60. Spyropoulos AC.. Brave new world: the current and future use of novel anticoagulants. J Thromb Res. 2008 ; 123 (1). S29 - S35
61. Eriksson BL, Dahl OE, Rosencher N, et al. Dabigatran etexilate versus enoxaparin for prevention of venous thromboembolism after total hip replacement: a randomized, double-blind, non-inferiority trial. Lancet. 2007 ; 370 (9591). 949-956 (Pubitemid 47393577)
62. 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 (11). 2178-2185 (Pubitemid 47617868)
63. Ginsberg JS, Davidson BL, Comp PC, et al. The oral thrombin inhibitor dabigatran etexilate vs the North American enoxaparin regimen for the prevention of venous thromboembolism after knee arthroplasty surgery. J Arthroplasty. 2009 ; 1 (24). 1-9
64. Wolowacz SE, Roskell NS, Plumb JM, Caprini JA, Eriksson BI.. Efficacy and safety of dabigatran etexilate for the prevention of venous thromboembolism following total hip or knee arthroplasty. A meta-analysis. Thromb Haemost. 2009 ; 101 (1). 77-85
65. Schulman S, Kearon C, Kakkar AK, et al. RE-COVER Study Group. Dabigatran versus Warfarin in the Treatment of Acute Venous Thromboembolism. New Engl J Med. 2009 ; 361 (24). 2342-2352
66. Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus Warfarin in Patients with Atrial Fibrillation. N Engl J Med. 2009 ; 361 (12). 1139-1151
67. Gage BF.. Can We Rely on RE-LY?. N Engl J Med. 2009 ; 361 (12). 1200-1202
68. Wienan W, Stassen JM, Priepke H, Ries UJ, Hauel N.. Effects of the direct thrombin inhibitor dabigatran and its orally active prodrug, dabigatran etexilate, on thrombus formation and bleeding time in rats. Thromb Haemost. 2007 ; 98 (2). 333-338 (Pubitemid 47250236)
69. Young G, Yonekawa KE, Nakagawa PA, et al. Recombinant activated factor VII effectively reverses the anticoagulant effects of heparin, enoxaparin, fondaparinux, argatroban, and bivalirudin ex vivo as measured using thromboelastography. Blood Coagul Fibrinolysis. 2007 ; 18 (6). 547-553 (Pubitemid 47344302)
70. Fenyesi T, Jorg I, Harenberg J.. Monitoring of anticoagulant effects of direct thrombin inhibitors. Semin Thromb Hemost. 2002 ; 28 (4). 361-368 (Pubitemid 34971923)
71. Nurmohamed MT, Berckmans RJ, Morrien-Salomons WM, et al. Monitoring anticoagulant therapy by activated partial thromboplastin time: hirudin assessment: an evaluation of native blood and plasma assays. Thromb Haemost. 1994 ; 72 (5). 685-692 (Pubitemid 24341043)
72. Callas DD, Fareed J.. Comparative anticoagulant effects of various thrombin inhibitors, as determined in the ecarin clotting time method. Thromb Res. 1996 ; 83 (6). 463-468 (Pubitemid 26328718)
73. Casserly IP, Kereiakes DJ, Gray WA, et al. Point-of-care ecarin clotting time versus activated clotting time in correlation with bivalirudin concentration. Thromb Res. 2004 ; 113 (2). 115-121 (Pubitemid 38534488)
74. Cho L, Kottke-Marchant K, Lincoff AM, et al. Correlation of point-of-care ecarin clotting time versus activated clotting time with bivalirudin concentrations. Am J Cardiol. 2003 ; 91 (9). 1110-1112