Novel oral anticoagulants : Implications in the perioperative setting

Anesthesiology

Volumn 113, Issue 3, 2010, Pages 726-745

  Levy, Jerrold H ^a,b   Key, Nigel S ^b   Azran, Marc S ^a  

^a EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF NORTH CAROLINA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTICOAGULANT AGENT; ANTIRETROVIRUS AGENT; APIXABAN; CARBAMAZEPINE; DABIGATRAN ETEXILATE; ENOXAPARIN; FLUCONAZOLE; FONDAPARINUX; HEPARIN; ITRACONAZOLE; KETOCONAZOLE; LOW MOLECULAR WEIGHT HEPARIN; PHENOBARBITAL; PHENYTOIN; POSACONAZOLE; RIVAROXABAN; WARFARIN;

BLEEDING; CLINICAL TRIAL; COST EFFECTIVENESS ANALYSIS; DEEP VEIN THROMBOSIS; DRUG BINDING; DRUG BIOAVAILABILITY; DRUG EFFICACY; DRUG ELIMINATION; DRUG HALF LIFE; DRUG POTENTIATION; DRUG SAFETY; DRUG TOLERABILITY; HEART ATRIUM FIBRILLATION; HEPARIN INDUCED THROMBOCYTOPENIA; HUMAN; NONHUMAN; PERIOPERATIVE PERIOD; POSTOPERATIVE PERIOD; PRIORITY JOURNAL; REVIEW; RISK FACTOR; TOTAL HIP PROSTHESIS; TOTAL KNEE REPLACEMENT; VENOUS THROMBOEMBOLISM; ANIMAL; BLOOD CLOTTING; DRUG EFFECT; KNEE ARTHROPLASTY; METHODOLOGY; ORAL DRUG ADMINISTRATION; PHYSIOLOGY;

ADMINISTRATION, ORAL; ANIMALS; ANTICOAGULANTS; ARTHROPLASTY, REPLACEMENT, KNEE; BLOOD COAGULATION; HUMANS; PERIOPERATIVE CARE; VENOUS THROMBOEMBOLISM;

EID: 77956990674     PISSN: 00033022     EISSN: 15281175     Source Type: Journal    
DOI: 10.1097/ALN.0b013e3181ebdb15     Document Type: Review

References (141)

1. Seré KM, Hackeng TM: Basic mechanisms of hemostasis. Semin Vasc Med 2003; 3:3-12
2. Laposata M, Green D, Van Cott EM, Barrowcliffe TW, Goodnight SH, Sosolik RC: College of American Pathologists Conference XXXI on laboratory monitoring of anticoagulant therapy: The clinical use and laboratory monitoring of low-molecular-weight heparin, danaparoid, hirudin and related compounds, and argatroban. Arch Pathol Lab Med 1998; 122:799-807
3. Collins R, Scrimgeour A, Yusuf S, Peto R: Reduction in fatal pulmonary embolism and venous thrombosis by perioperative administration of subcutaneous heparin. Overview of results of randomized trials in general, orthopedic, and urologic surgery. N Engl J Med 1988; 318:1162-1173
4. Kearon C: Natural history of venous thromboembolism. Circulation 2003; 107:I22-30
5. Ollendorf DA, Vera-Llonch M, Oster G: Cost of venous thromboembolism following major orthopedic surgery in hospitalized patients. Am J Health Syst Pharm 2002; 59:1750-1754
6. Oster G, Ollendorf DA, Vera-Llonch M, Hagiwara M, Berger A, Edelsberg J: Economic consequences of venous thromboembolism following major orthopedic surgery. Ann Pharmacother 2004; 38:377-382
7. Spyropoulos AC, Lin J: Direct medical costs of venous thromboembolism and subsequent hospital readmission rates: An administrative claims analysis from 30 managed care organizations. J Manag Care Pharm 2007; 13:475-486
8. Cohen AT, Tapson VF, Bergmann JF, Goldhaber SZ, Kakkar AK, Deslandes B, Huang W, Zayaruzny M, Emery L, Anderson FA Jr, ENDORSE Investigators: Venous thromboembolism risk and prophylaxis in the acute hospital care setting (ENDORSE study): A multinational cross-sectional study. Lancet 2008; 371:387-394
9. Mammen EF: Pathogenesis of venous thrombosis. Chest 1992; 102:640S- 4S.
10. Heit JA, Silverstein MD, Mohr DN, Petterson TM, O'Fallon WM, Melton LJ 3rd: Risk factors for deep vein thrombosis and pulmonary embolism: A populationbased case-control study. Arch Intern Med 2000; 160: 809-815
11. Rahman M, Beattie J: Surgery and venous thromboembolism. Pharm J 2004; 273:687-689
12. Geerts WH, Bergqvist D, Pineo GF, Heit JA, Samama CM, Lassen MR, Colwell CW, American College of Chest Physicians: Prevention of venous thromboembolism: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008; 133:381S- 453S
13. Cardiovascular Disease Educational and Research Trust, Cyprus Cardiovascular Disease Educational and Research Trust, European Venous Forum, International Surgical Thrombosis Forum, International Union of Angiology, Union Internationale de Phlébologie: Prevention and treatment of venous thromboembolism. International Consensus Statement (guidelines according to scientific evidence). Int Angiol 2006; 25:101-161
14. Guyatt GH, Cook DJ, Jaeschke R, Pauker SG, Schünemann HJ: Grades of recommendation for antithrombotic agents: American College of Chest Physicians Evidence- Based Clinical Practice Guidelines (8th Edition). Chest 2008; 133:123S-31S
15. White RH, Zhou H, Romano PS: Incidence of symptomatic venous thromboembolism after different elective or urgent surgical procedures. Thromb Haemost 2003; 90: 446-455
16. Friedman RJ, Gallus AS, Cushner FD, Fitzgerald G, Anderson FA Jr, Global Orthopaedic Registry Investigators: Physician compliance with guidelines for deepvein thrombosis prevention in total hip and knee arthroplasty. Curr Med Res Opin 2008; 24:87-97
17. White RH, Romano PS, Zhou H, Rodrigo J, Bargar W: Incidence and time course of thromboembolic outcomes following total hip or knee arthroplasty. Arch Intern Med 1998; 158:1525-1531
18. Ziomek S, Read RC, Tobler HG, Harrell JE Jr, Gocio JC, Fink LM, Ranval TJ, Ferris EJ, Harshfield DL, McFarland DR: Thromboembolism in patients undergoing thoracotomy. Ann Thorac Surg 1993; 56:223-226
19. Kalweit G, Huwer H, Volkmer I, Petzold T, Gams E: Pulmonary embolism: A frequent cause of acute fatality after lung resection. Eur J Cardiothorac Surg 1996; 10: 242-246
20. Roselli EE, Murthy SC, Rice TW, Houghtaling PL, Pierce CD, Karchmer DP, Blackstone EH: Atrial fibrillation complicating lung cancer resection. J Thorac Cardiovasc Surg 2005; 130:438-444
21. Josa M, Siouffi SY, Silverman AB, Barsamian EM, Khuri SF, Sharma GV: Pulmonary embolism after cardiac surgery. J Am Coll Cardiol 1993; 21:990-996
22. Maisel WH, Rawn JD, Stevenson WG: Atrial fibrillation after cardiac surgery. Ann Intern Med 2001; 135:1061-1073
23. Warkentin TE, Greinacher A: Heparin-induced thrombocytopenia and cardiac surgery. Ann Thorac Surg 2003; 76:2121-2131
24. Smythe MA, Koerber JM, Mattson JC: The incidence of recognized heparin-induced thrombocytopenia in a large, tertiary care teaching hospital. Chest 2007; 131: 1644-1649
25. Singer DE, Albers GW, Dalen JE, Fang MC, Go AS, Halperin JL, Lip GY, Manning WJ, American College of Chest Physicians: Antithrombotic therapy in atrial fibrillation: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008; 133:546S-92S
26. Warkentin TE, Greinacher A, Koster A, Lincoff AM, American College of Chest Physicians: Treatment and prevention of heparin-induced thrombocytopenia: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008; 133:340S- 80S
27. Goldhaber SZ, Schoepf UJ: Pulmonary embolism after coronary artery bypass grafting. Circulation 2004; 109: 2712-2715
28. Reis SE, Polak JF, Hirsch DR, Cohn LH, Creager MA, Donovan BC, Goldhaber SZ: Frequency of deep venous thrombosis in asymptomatic patients with coronary artery bypass grafts. Am Heart J 1991; 122:478-482
29. Hoffman M, Monroe DM 3rd: A cell-based model of hemostasis. Thromb Haemost 2001; 85:958-965
30. Aird WC: Vascular bed-specific thrombosis. J Thromb Haemost 2007; 5(Suppl 1):283-291
31. Roberts HR, Monroe DM, Escobar MA: Current concepts of hemostasis: Implications for therapy. ANESTHESIOLOGY 2004; 100:722-730
32. Hirsh J, Bauer KA, Donati MB, Gould M, Samama MM, Weitz JI, American College of Chest Physicians: Parenteral anticoagulants: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008; 133:141S-59S
33. Blick SK, Orman JS, Wagstaff AJ, Scott LJ: Fondaparinux sodium: A review of its use in the management of acute coronary syndromes. Am J Cardiovasc Drugs 2008; 8:113-125
34. Warkentin TE, Cook RJ, Marder VJ, Sheppard JA, Moore JC, Eriksson BI, Greinacher A, Kelton JG: Anti-platelet factor 4/heparin antibodies in orthopedic surgery patients receiving antithrombotic prophylaxis with fondaparinux or enoxaparin. Blood 2005; 106:3791-3796
35. Lisman T, Bijsterveld NR, Adelmeijer J, Meijers JC, Levi M, Nieuwenhuis HK, De Groot PG: Recombinant factor VIIa reverses the in vitro and ex vivo anticoagulant and profibrinolytic effects of fondaparinux. J Thromb Haemost 2003; 1:2368-2373
36. Ansell J, Hirsh J, Hylek E, Jacobson A, Crowther M, Palareti G, American College of Chest Physicians: Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008; 133:160S-98S
37. Levy JH, Tanaka KA, Dietrich W: Perioperative hemostatic management of patients treated with vitamin K antagonists. ANESTHESIOLOGY 2008; 109:918-926
38. Rosencher N, Bonnet MP, Sessler DI: Selected new antithrombotic agents and neuraxial anaesthesia for major orthopaedic surgery: Management strategies. Anaesthesia 2007; 62:1154-1160
39. Horlocker TT, Wedel DJ, Benzon H, Brown DL, Enneking FK, Heit JA, Mulroy MF, Rosenquist RW, Rowlingson J, Tryba M, Yuan CS: Regional anesthesia in the anticoagulated patient: Defining the risks (the second ASRA Consensus Conference on Neuraxial Anesthesia and Anticoagulation). Reg Anesth Pain Med 2003; 28:172-197
40. Gogarten W: The influence of new antithrombotic drugs on regional anesthesia. Curr Opin Anaesthesiol 2006; 19:545-550
41. Singelyn FJ, Verheyen CC, Piovella F, Van Aken HK, Rosencher N, EXPERT Study Investigators: The safety and efficacy of extended thromboprophylaxis with fondaparinux after major orthopedic surgery of the lower limb with or without a neuraxial or deep peripheral nerve catheter: The EXPERT Study. Anesth Analg 2007; 105:1540-1547
42. Schulman S, Beyth RJ, Kearon C, Levine MN, American College of Chest Physicians: Hemorrhagic complications of anticoagulant and thrombolytic treatment: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008; 133:257S-98S
43. Weitz JI, Bates SM: New anticoagulants. J Thromb Haemost 2005; 3:1843-1853
44. Ansell J: Factor Xa or thrombin: Is factor Xa a better target? J Thromb Haemost 2007; 5(Suppl 1):60-64
45. Weitz JI: Factor Xa or thrombin: Is thrombin a better target? J Thromb Haemost 2007; 5(Suppl 1):65-67
46. Herbert JM, Hérault JP, Bernat A, van Amsterdam RG, Lormeau JC, Petitou M, van Boeckel C, Hoffmann P, Meuleman DG: Biochemical and pharmacological properties of SANORG 34006, a potent and long-acting synthetic pentasaccharide. Blood 1998; 91:4197-4205
47. Weitz JI: New anticoagulants for treatment of venous thromboembolism. Circulation 2004; 110:I19 -26
48. van Gogh Investigators, Buller HR, Cohen AT, Davidson B, Decousus H, Gallus AS, Gent M, Pillion G, Piovella F, Prins MH, Raskob GE: Idraparinux versus standard therapy for venous thromboembolic disease. N Engl J Med 2007; 357:1094-1104
49. van Gogh Investigators, Buller HR, Cohen AT, Davidson B, Decousus H, Gallus AS, Gent M, Pillion G, Piovella F, Prins MH, Raskob GE: Extended prophylaxis of venous thromboembolism with idraparinux. N Engl J Med 2007; 357:1105-1112
50. Amadeus Investigators, Bousser MG, Bouthier J, Büller HR, Cohen AT, Crijns H, Davidson BL, Halperin J, Hankey G, Levy S, Pengo V, Prandoni P, Prins MH, Tomkowski W, Torp-Pedersen C, Wyse DG: Comparison of idraparinux with vitamin K antagonists for prevention of thromboembolism in patients with atrial fibrillation: A randomised, open-label, non-inferiority trial. Lancet 2008; 371:315-321
51. Paty I, Trellu M, Destors J, Cortez P, Boelle E, Sanderink G. Reversibility of the anticoagulant activity of idrabiotaparinux (biotinylated idraparinux) by avidin in healthy subjects and patients (abstract). J Thromb Haemost 2009; 7(Suppl 2): Abstract OC-WE-006
52. Acostamadiedo JM, Iyer UG, Owen J: Danaparoid sodium. Expert Opin Pharmacother 2000; 1:803-814
53. Perzborn E, Strassburger J, Wilmen A, Pohlmann J, Roehrig S, Schlemmer KH, Straub A: In vitro and in vivo studies of the novel antithrombotic agent BAY 59 -7939 -an oral, direct Factor Xa inhibitor. J Thromb Haemost 2005; 3:514-521
54. 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; 78:412-421
55. Eriksson BI, Quinlan DJ, Weitz JI: Comparative pharmacodynamics and pharmacokinetics of oral direct thrombin and factor Xa inhibitors in development. Clin Pharmacokinet 2009; 48:1-22
56. Walenga JM, Prechel M, Jeske WP, Hoppensteadt D, Maddineni J, Iqbal O, Messmore HL, Bakhos M: Rivaroxaban- an oral, direct Factor Xa inhibitor-has potential for the management of patients with heparin-induced thrombocytopenia. Br J Haematol 2008; 143:92-99
57. Weinz C, Schwarz T, Kubitza D, Mueck W, Lang D: Metabolism and excretion of rivaroxaban, an oral, direct factor Xa inhibitor, in rats, dogs, and humans. Drug Metab Dispos 2009; 37:1056-1064
58. Eriksson BI, Borris LC, Friedman RJ, Haas S, Huisman MV, Kakkar AK, Bandel TJ, Beckmann H, Muehlhofer E, Misselwitz F, Geerts W, RECORD1 Study Group: Rivaroxaban versus enoxaparin for thromboprophylaxis after hip arthroplasty. N Engl J Med 2008; 358:2765-2775 (Pubitemid 351930851)
59. Kakkar AK, Brenner B, Dahl OE, Eriksson BI, Mouret P, Muntz J, Soglian AG, Pap AF, Misselwitz F, Haas S, 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
60. Lassen MR, Ageno W, Borris LC, Lieberman JR, Rosencher N, Bandel TJ, Misselwitz F, Turpie AG, RECORD3 Investigators: Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty. N Engl J Med 2008; 358:2776-2786 (Pubitemid 351930852)
61. Turpie AGG, Lassen MR, Davidson BL, Bauer KA, Gent M, Kwong LM, Cushner FD, Lotke PA, Berkowitz SD, Bandel TJ, Benson A, Misselwitz F, Fisher WD, RECORD4 Investigators: Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty (RECORD4): A randomised trial. Lancet 2009; 373: 1673-1680
62. Turpie AG, Lassen MR, Kakkar A, Eriksson BI, Misselwitz F, Bandel TJ, Homering M, Westermeler T, Gent M: A pooled analysis of four pivotal studies of rivaroxaban for the prevention of venous thromboembolism after orthopaedic surgery: Effect on symptomatic venous thromboembolism, death, and bleeding (abstract). Blood 2008; 112:Abstract 36
63. 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: 981-990
64. Kubitza D, Becka M, Mueck W, Zuehlsdorf M. Co-administration of rivaroxaban-a novel, oral, direct Factor Xa inhibitor-and clopidogrel in healthy subjects (abstract). Eur Heart J 2007; 28(Suppl 1):189 Abstract P1272
65. 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). J Thromb Haemost 2007; 5(Suppl 2):Abstract P-W-640
66. Gruber A, Marzec UM, Buetehorn U, Hanson S, Perzborn E. Potential of activated prothrombin complex concentrate and activated Factor VII to reverse the anticoagulant effects of rivaroxaban in primates (abstract). Blood 2008; 112:Abstract 3825
67. Perzborn E, Tinel H. FEIBA reverses the effects of a high dose of rivaroxaban in rats (abstract). Pathophysiol Haemost Thromb 2008; 36:A40 Abstract P061
68. Perzborn E, Trabandt A, Selbach K, Tinel H. Prothrombin complex concentrate reverses the effects of highdose rivaroxaban in rats (abstract). J Thromb Haemost 2009; 7(Suppl 2):379 Abstract PP-MO-183
69. Lu G, DeGuzman F, Lakhotia S, Hollenbach SJ, Phillips DR, Sinha U. Recombinant antidote for reversal of anticoagulation by Factor Xa inhibitors (abstract). Blood 2008; 112:Abstract 983
70. Lu G, Luan P, Hollenbach S, Abe K, DeGuzman F, Siu G, Hutchaleelaha A, Inagaki M, Conley PB, Phillips DR, Sinha U. Reconstructed recombinant factor Xa as an antidote to reverse anticoagulation by factor Xa inhibitors (abstract). J Thromb Haemost 2009; 7(Suppl 2): Abstract OC-TH-107
71. Samama MM, Martinoli JL, LeFlem L, Guinet C, Plu- Bureau G, Depasse F, Perzborn E: Assessment of laboratory assays to measure rivaroxaban-an oral, direct factor Xa inhibitor. Thromb Haemost 2010; 103:815-825
72. Perzborn E, Harwardt M, Samama M. Assessment of Factor Xa chromogenic assays for measuring the pharmacodynamics of rivaroxaban-an oral, direct Factor Xa inhibitor (abstract). J Thromb Haemost 2009; 7(Suppl 2): 379 Abstract PP-MO-185
73. Mega JL, Braunwald E, Mohanavelu S, Burton P, Poulter R, Misselwitz F, Hricak V, Barnathan ES, Bordes P, Witkowski A, Markov V, Oppenheimer L, Gibson CM, ATLAS ACS-TIMI 46 study group: Rivaroxaban versus placebo in patients with acute coronary syndromes (ATLAS ACS-TIMI 46): A randomised, double-blind, phase II trial. Lancet 2009; 374:29-38
74. Raghavan N, Frost CE, Yu Z, He K, Zhang H, Humphreys WG, Pinto D, Chen S, Bonacorsi S, Wong PC, Zhang D: Apixaban metabolism and pharmacokinetics after oral administration to humans. Drug Metab Dispos 2009; 37:74-81
75. Carreiro J, Ansell J: Apixaban, an oral direct Factor Xa inhibitor: Awaiting the verdict. Expert Opin Investig Drugs 2008; 17:1937-1945
76. Wong PC, Watson CA, Crain EJ: Arterial antithrombotic and bleeding time effects of apixaban, a direct factor Xa inhibitor, in combination with antiplatelet therapy in rabbits. J Thromb Haemost 2008; 6:1736-1741
77. Wang L, Zhang D, Raghavan N, Yao M, Ma L, Frost CE, Maxwell BD, Chen SY, He K, Goosen TC, Humphreys WG, Grossman SJ: In vitro assessment of metabolic drug-drug interaction potential of apixaban through cytochrome P450 phenotyping, inhibition, and induction studies. Drug Metab Dispos 2010; 38:448-458
78. Barrett YC, Wang J, Yu Z, Shenker A, Knabb R, Mohan P: Apixaban treatment decreases coagulation activity in patients with acute deep-vein thrombosis (abstract). Blood 2008; 112:Abstract 1982
79. 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
80. Lassen MR, Raskob GE, Gallus A, Pineo G, Chen D, Hornick P, ADVANCE-2 investigators: Apixaban versus enoxaparin for thromboprophylaxis after knee replacement (ADVANCE-2): A randomised double-blind trial. Lancet 2010; 375:807-815
81. APPRAISE Steering Committee and Investigators, Alexander JH, Becker RC, Bhatt DL, Cools F, Crea F, Dellborg M, Fox KA, Goodman SG, Harrington RA, Huber K, Husted S, Lewis BS, Lopez-Sendon J, Mohan P, Montalescot G, Ruda M, Ruzyllo W, Verheugt F, Wallentin L: 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; 119:2877-2885
82. Eriksson BI, Turpie AG, Lassen MR, Prins MH, Agnelli G, Kälebo P, Gaillard ML, Meems L, ONYX study group: A dose escalation study of YM150, an oral direct factor Xa inhibitor, in the prevention of venous thromboembolism in elective primary hip replacement surgery. J Thromb Haemost 2007; 5:1660-1665
83. Eriksson BI, Turpie AGG, Lassen M, Prins MH, Agnelli G, Kalebo P, Wetherill G. Once daily YM150, an oral direct factor Xa inhibitor, for prevention of venous thromboembolism in patients undergoing elective primary hip replacement (abstract). Blood 2008; 112:Abstract 309
84. 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 (abstract). Blood 2008; 112:Abstract 34
85. 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 (abstract). Blood 2008; 112:Abstract 33
86. Turpie AG, Bauer KA, Davidson BL, Fisher WD, Gent M, Huo MH, Sinha U, Gretler DD, EXPERT Study Group: 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
87. Cohen AT, Armstrong D, Gazdzik T, Ryge C, Pak R, Mandema J, Boyd R, McBride S, DiCarlo LA: An adaptivedesign dose-ranging study of PD 0348292, a new oral Factor Xa inhibitor, for thromboprophylaxis after total knee replacement surgery (abstract). Blood 2008; 112: Abstract 980
88. Guertin KR, Choi YM: The discovery of the Factor Xa inhibitor otamixaban: From lead identification to clinical development. Curr Med Chem 2007; 14:2471-2481
89. Cohen M, Bhatt DL, Alexander JH, Montalescot G, Bode C, Henry T, Tamby JF, Saaiman J, Simek S, De Swart J, SEPIA-PCI Trial Investigators: Randomized, doubleblind, dose-ranging study of otamixaban, a novel, parenteral, short-acting direct factor Xa inhibitor, in percutaneous coronary intervention: The SEPIA-PCI trial. Circulation 2007; 115:2642-2651
90. Christersson C, Oldgren J, Bylock A, Wallentin L, Siegbahn A: Long-term treatment with ximelagatran, an oral direct thrombin inhibitor, persistently reduces the coagulation activity after a myocardial infarction. J Thromb Haemost 2005; 3:2245-2253
91. Wallentin L, Wilcox RG, Weaver WD, Emanuelsson H, Goodvin A, Nystrom P, Bylock A, ESTEEM Investigators: Oral ximelagatran for secondary prophylaxis after myocardial infarction: The ESTEEM randomised controlled trial. Lancet 2003; 362:789-797
92. Wolzt M, Boström SL, Svensson M, Wählander K, Grind M, Sarich TC: Effects of the oral direct thrombin inhibitor ximelagatran on p-selectin expression and thrombin generation in atrial fibrillation. Pathophysiol Haemost Thromb 2003; 33:68-74 (Pubitemid 37449281)
93. Albers GW, Diener HC, Frison L, Grind M, Nevinson M, Partridge S, Halperin JL, Horrow J, Olsson SB, Petersen P, Vahanian A, 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: 690-698
94. 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): Randomised controlled trial. Lancet 2003; 362:1691-1698
95. Stangier J, Rathgen K, Stähle 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
96. Stangier J, Clemens A: Pharmacology, pharmacokinetics, and pharmacodynamics of dabigatran etexilate, an oral direct thrombin inhibitor. Clin Appl Thromb Hemost 2009; 15(Suppl 1):9S-16S
97. Eriksson BI, Kurth AA, Friedman RJ, Schnee JM, Clemens A, Noack H, Caprini JA. Risk of bleeding with dabigatran etexilate in patients undergoing major orthopaedic surgery is not increased by concomitant use of non-steroidal anti-inflammatory drugs or acetylsalicylic acid (abstract). J Thromb Haemost 2009; 7(Suppl 2):379 Abstract PP-MO-167
98. Merli G, Spyropoulos AC, Caprini JA: Use of emerging oral anticoagulants in clinical practice: Translating results from clinical trials to orthopedic and general surgical patient populations. Ann Surg 2009; 250:219-228
99. Eriksson BI, Dahl OE, Rosencher N, Kurth AA, van Dijk CN, Frostick SP, Prins MH, Hettiarachchi R, Hantel S, Schnee J, Büller HR, RE-NOVATE Study Group: Dabigatran etexilate versus enoxaparin for prevention of venous thromboembolism after total hip replacement: A randomised, double-blind, non-inferiority trial. Lancet 2007; 370:949-956 (Pubitemid 47393577)
100. Eriksson BI, Dahl OE, Rosencher N, Kurth AA, van Dijk CN, Frostick SP, Kälebo P, Christiansen AV, Hantel S, Hettiarachchi R, Schnee J, Büller HR, RE-MODEL Study Group: 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; 5:2178-2185 (Pubitemid 47617868)
101. RE-MOBILIZE Writing Committee, Ginsberg JS, Davidson BL, Comp PC, Francis CW, Friedman RJ, Huo MH, Lieberman JR, Muntz JE, Raskob GE, Clements ML, Hantel S, Schnee JM, Caprini JA: 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
102. Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, Pogue J, Reilly PA, Themeles E, Varrone J, Wang S, Alings M, Xavier D, Zhu J, Diaz R, Lewis BS, Darius H, Diener HC, Joyner CD, Wallentin L, RE-LY Steering Committee and Investigators: Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009; 361:1139-1151
103. Schulman S, Kearon C, Kakkar AK, Mismetti P, Schellong S, Eriksson H, Baanstra D, Schnee J, Goldhaber SZ, RE-COVER Study Group: Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med 2009; 361:2342-2352
104. Warkentin TE, Greinacher A, Koster A: Bivalirudin. Thromb Haemost 2008; 99:830-839
105. Moen MD, Keating GM, Wellington K: Bivalirudin: A review of its use in patients undergoing percutaneous coronary intervention. Drugs 2005; 65:1869-1891
106. Stone GW, McLaurin BT, Cox DA, Bertrand ME, Lincoff AM, Moses JW, White HD, Pocock SJ, Ware JH, Feit F, Colombo A, Aylward PE, Cequier AR, Darius H, Desmet W, Ebrahimi R, Hamon M, Rasmussen LH, Rupprecht HJ, Hoekstra J, Mehran R, Ohman EM, ACUITY Investigators: Bivalirudin for patients with acute coronary syndromes. N Engl J Med 2006; 355:2203-2216
107. Stone GW, Witzenbichler B, Guagliumi G, Peruga JZ, Brodie BR, Dudek D, Kornowski R, Hartmann F, Gersh BJ, Pocock SJ, Dangas G, Wong SC, Kirtane AJ, Parise H, Mehran R, HORIZONS-AMI Trial Investigators: Bivalirudin during primary PCI in acute myocardial infarction. N Engl J Med 2008; 358:2218-2230
108. Brodie BR: What anti-thrombotic therapy is best with primary PCI for acute ST elevation myocardial infarction: How should the HORIZONS trial change current practice? Catheter Cardiovasc Interv 2008; 71:816-821
109. Koster A, Buz S, Krabatsch T, Yeter R, Hetzer R: Bivalirudin anticoagulation during cardiac surgery: A singlecenter experience in 141 patients. Perfusion 2009; 24: 7-11
110. Dyke CM, Aldea G, Koster A, Smedira N, Avery E, Aronson S, Spiess BD, Lincoff AM: Off-pump coronary artery bypass with bivalirudin for patients with heparin-induced thrombocytopenia or antiplatelet factor four/ heparin antibodies. Ann Thorac Surg 2007; 84:836-839
111. Koster A, Dyke CM, Aldea G, Smedira NG, McCarthy HL 2nd, Aronson S, Hetzer R, Avery E, Spiess B, Lincoff AM: Bivalirudin during cardiopulmonary bypass in patients with previous or acute heparin-induced thrombocytopenia and heparin antibodies: Results of the CHOOSE-ON trial. Ann Thorac Surg 2007; 83:572-577
112. Merry AF, Raudkivi PJ, Middleton NG, McDougall JM, Nand P, Mills BP, Webber BJ, Frampton CM, White HD: Bivalirudin versus heparin and protamine in off-pump coronary artery bypass surgery. Ann Thorac Surg 2004; 77:925-931
113. Koster A, Spiess B, Jurmann M, Dyke CM, Smedira NG, Aronson S, Lincoff MA: Bivalirudin provides rapid, effective, and reliable anticoagulation during off-pump coronary revascularization: Results of the "EVOLUTION OFF" trial. Anesth Analg 2006; 103:540-544
114. Dyke CM, Smedira NG, Koster A, Aronson S, McCarthy HL 2nd, Kirshner R, Lincoff AM, Spiess BD: A comparison of bivalirudin to heparin with protamine reversal in patients undergoing cardiac surgery with cardiopulmonary bypass: The EVOLUTION-ON study. J Thorac Cardiovasc Surg 2006; 131:533-539
115. Petros S: Lepirudin in the management of patients with heparin-induced thrombocytopenia. Biologics 2008; 2:481-490
116. Riess FC, Löwer C, Seelig C, Bleese N, Kormann J, Müller-Berghaus G, Pötzsch B: Recombinant hirudin as a new anticoagulant during cardiac operations instead of heparin: Successful for aortic valve replacement in man. J Thorac Cardiovasc Surg 1995; 110:265-267
117. Riess FC, Poetzsch B, Madlener K, Cramer E, Doll KN, Doll S, Lorke DE, Kormann J, Mueller-Berghaus G: Recombinant hirudin for cardiopulmonary bypass anticoagulation: A randomized, prospective, and heparin-controlled pilot study. Thorac Cardiovasc Surg 2007; 55: 233-238
118. Lubenow N, Eichler P, Lietz T, Greinacher A, Hit Investigators Group: Lepirudin in patients with heparin-induced thrombocytopenia-results of the third prospective study (HAT-3) and a combined analysis of HAT-1, HAT-2, and HAT-3. J Thromb Haemost 2005; 3:2428-2436
119. Eichler P, Friesen HJ, Lubenow N, Jaeger B, Greinacher A: Antihirudin antibodies in patients with heparin-induced thrombocytopenia treated with lepirudin: Incidence, effects on aPTT, and clinical relevance. Blood 2000; 96:2373-2378
120. Wittkowsky AK, Kondo LM: Lepirudin dosing in dialysisdependent renal failure. Pharmacotherapy 2000; 20:1123-1128
121. Matheson AJ, Goa KL: Desirudin: A review of its use in the management of thrombotic disorders. Drugs 2000; 60:679-700
122. Eriksson BI, Wille-Jørgensen P, Kälebo P, Mouret P, Rosencher N, Bösch P, Baur M, Ekman S, Bach D, Lindbratt S, Close P: A comparison of recombinant hirudin with a low-molecular-weight heparin to prevent thromboembolic complications after total hip replacement. N Engl J Med 1997; 337:1329-1335
123. Eriksson BI, Ekman S, Lindbratt S, Baur M, Bach D, Torholm C, Kälebo P, Close P: 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; 79:326-333
124. van den Bos AA, Deckers JW, Heyndrickx GR, Laarman GJ, Suryapranata H, Zijlstra F, Close P, Rijnierse JJ, Buller HR, Serruys PW: Safety and efficacy of recombinant hirudin (CGP 39 393) versus heparin in patients with stable angina undergoing coronary angioplasty. Circulation 1993; 88:2058-2066
125. The Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) IIb investigators: A comparison of recombinant hirudin with heparin for the treatment of acute coronary syndromes. N Engl J Med 1996; 335: 775-782
126. Hallman SE, Hebbar L, Robison J, Uber WE: The use of argatroban for carotid endarterectomy in heparin-induced thrombocytopenia. Anesth Analg 2005; 100:946-948
127. Martin ME, Kloecker GH, Laber DA: Argatroban for anticoagulation during cardiac surgery. Eur J Haematol 2007; 78:161-166
128. Lewis BE, Wallis DE, Berkowitz SD, Matthai WH, Fareed J, Walenga JM, Bartholomew J, Sham R, Lerner RG, Zeigler ZR, Rustagi PK, Jang IK, Rifkin SD, Moran J, Hursting MJ, Kelton JG, ARG-911 Study Investigators: Argatroban anticoagulant therapy in patients with heparin- induced thrombocytopenia. Circulation 2001; 103: 1838-1843
129. 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; 163:1849-1856
130. Kathiresan S, Shiomura J, Jang IK: Argatroban. J Thromb Thrombolysis 2002; 13:41-47
131. Walenga JM, Ahmad S, Hoppensteadt D, Iqbal O, Hursting MJ, Lewis BE: Argatroban therapy does not generate antibodies that alter its anticoagulant activity in patients with heparin-induced thrombocytopenia. Thromb Res 2002; 105:401-405
132. Swan SK, Hursting MJ: The pharmacokinetics and pharmacodynamics of argatroban: Effects of age, gender, and hepatic or renal dysfunction. Pharmacotherapy 2000; 20:318-329
133. Eriksson BI, Quinlan DJ: Oral anticoagulants in development: Focus on thromboprophylaxis in patients undergoing orthopaedic surgery. Drugs 2006; 66:1411-1429
134. Dyke CK, Steinhubl SR, Kleiman NS, Cannon RO, Aberle LG, Lin M, Myles SK, Melloni C, Harrington RA, Alexander JH, Becker RC, Rusconi CP: First-in-human experience of an antidote-controlled anticoagulant using RNA aptamer technology: A phase 1a pharmacodynamic evaluation of a drug-antidote pair for the controlled regulation of factor IXa activity. Circulation 2006; 114: 2490-2497
135. Cohen MG, Purdy DA, Rossi JS, Grinfeld LR, Aberle LH, Greenbaum AB, Fry ET, Alexander JA, Rusconi CP, Becker RC: First clinical application of an actively re- versible direct factor IXa inhibitor in elective percutaneous coronary intervention (abstract). Eur Heart J 2009; 30:101 Abstract P686
136. Eriksson BI, Dahl OE, Lassen MR, Ward DP, Rothlein R, Davis G, Turpie AG, Fixit Study Group: Partial factor IXa inhibition with TTP889 for prevention of venous thromboembolism: An exploratory study. J Thromb Haemost 2008; 6:457-463
137. 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; 3:962-968
138. Saito H, Maruyama I, Shimazaki S, Yamamoto Y, Aikawa N, Ohno R, Hirayama A, Matsuda T, Asakura H, Nakashima M, Aoki N: 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
139. Herbert JM, Hérault JP, Bernat A, Savi P, Schaeffer P, Driguez PA, Duchaussoy P, Petitou M: SR123781A, a synthetic heparin mimetic. Thromb Haemost 2001; 85: 852-860
140. Bal dit Sollier C, Kang C, Berge N, Herault JP, Bonneau M, Herbert JM, Drouet L: Activity of a synthetic hexadecasaccharide (SanOrg123781A) in a pig model of arterial thrombosis. J Thromb Haemost 2004; 2:925-930
141. Lassen MR, Dahl O, Mismetti P, Zielske D, Turpie AG: SR123781A: A new once-daily synthetic oligosaccharide anticoagulant for thromboprophylaxis after total hip replacement surgery: The DRIVE (Dose Ranging Study in Elective Total Hip Replacement Surgery) study. J Am Coll Cardiol 2008; 51:1498-1504