Efficacy and safety of venous thromboembolism prophylaxis with apixaban in major orthopedic surgery

Therapeutics and Clinical Risk Management

Volumn 8, Issue , 2012, Pages 139-147

  Werth, Sebastian ^a   Halbritter, Kai ^a   Beyer Westendorf, Jan ^a  

^a UNIVERSITY HOSPITAL CARL GUSTAV CARUS   (Germany)

Author keywords

Apixaban; Dabigatran; Deep vein thrombosis; Edoxaban; Major orthopedic surgery; Rivaroxaban; Venous thromboembolism; VTE prophylaxis

Indexed keywords

AMIODARONE; ANTICOAGULANT AGENT; ANTIVITAMIN K; APIXABAN; BLOOD CLOTTING FACTOR 10A; CLARITHROMYCIN; CYCLOSPORIN A; DABIGATRAN; DABIGATRAN ETEXILATE; DRUG METABOLITE; EDOXABAN; ENOXAPARIN; ITRACONAZOLE; KETOCONAZOLE; QUINIDINE; RIFAMPICIN; RITONAVIR; RIVAROXABAN; TACROLIMUS; VERAPAMIL; WARFARIN;

BLEEDING; BLOOD CLOTTING; DEEP VEIN THROMBOSIS; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG DOSE ESCALATION; DRUG DOSE INCREASE; DRUG EFFICACY; DRUG ELIMINATION; DRUG EXCRETION; DRUG HALF LIFE; DRUG METABOLISM; DRUG POTENTIATION; DRUG SAFETY; EVENING DOSAGE; HUMAN; INTERNATIONAL NORMALIZED RATIO; MAJOR SURGERY; ORTHOPEDIC SURGERY; PATIENT MONITORING; PROTHROMBIN TIME; REVIEW; THROMBOSIS PREVENTION; VENOUS THROMBOEMBOLISM;

EID: 84875345821     PISSN: 11766336     EISSN: 1178203X     Source Type: Journal    
DOI: 10.2147/TCRM.S24238     Document Type: Review

References (58)

1. Hirsh J, Bauer KA, Donati MB, et al. American College of Chest Physicians. Parenteral anticoagulants: American College of Chest Physicians Evidence-based Clinical Practice Guidelines (8th ed). Chest. 2008;133(Suppl 6):141-159.
2. Hirsh J, Guyatt G, Albers GW, et al; American College of Chest Physician. Antithrombotic and thrombolytic therapy: American College of Chest Physicians Evidence-based Clinical Practice Guidelines (8th ed). Chest. 2008;133(Suppl 6):110-112.
3. Bergqvist D, Benoni G, Björgell O, et al. Low-molecular-weight heparin (enoxaparin) as prophylaxis against venous thromboembolism after total hip replacement. N Engl J Med. 1996;335(10):696-700.
4. Adolf J, Fritsche HM, Haas S, et al. Comparison of 3,000 IU aXa of the low molecular weight heparin certoparin with 5,000 IU aXa in prevention of deep vein thrombosis after total hip replacement. German Thrombosis Study Group. Int Angiol. 1999;18(2):122-126.
5. Lassen MR, Borris LC, Anderson BS, et al. Efficacy and safety of prolonged thromboprophylaxis with a low molecular weight heparin (dalteparin) after total hip arthroplasty: the Danish Prolonged Prophylaxis (DaPP) Study. Thromb Res. 1998;89(6):281-287.
6. Blanchard J, Meuwly JY, Leyvraz PF, et al. Prevention of deep-vein thrombosis after total knee replacement. Randomised comparison between a low-molecular-weight heparin (nadroparin) and mechanical prophylaxis with a foot-pump system. J Bone Joint Surg Br. 1999;81(4):654-659.
7. Wilke T, Moock J, Müller S, Pfannkuche M, Kurth A. Nonadherence in outpatient thrombosis prophylaxis with low molecular weight heparins after major orthopaedic surgery. Clin Orthop Relat Res. 2010;468(9):2437-2453.
8. Bergqvist D, Jönsson B. Cost-effectiveness of prolonged administration of a low molecular weight heparin for the prevention of deep venous thrombosis following total hip replacement. Value Health. 1999;2(4):288-294.
9. Turpie AG, Bauer KA, Eriksson BI, Lassen MR. Fondaparinux vs enoxaparin for the prevention of venous thromboembolism in major orthopedic surgery: a meta-analysis of 4 randomized double-blind studies. Arch Intern Med. 2002;162(16):1833-1840.
10. Eriksson BI, Dahl OE, Rosencher N, et al; 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(9591):949-956.
11. 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(26):2765-2775.
12. 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(26):2776-2786.
13. Turpie AG, Lassen MR, Davidson BL, et al; RECORD4 Investigators. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty (RECORD4): a randomised trial. Lancet. 2009;373(9676):1673-1680.
14. 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(6):594-604.
15. Lassen MR, Gallus A, Raskob GE, Pineo G, Chen D, Ramirez LM; ADVANCE-3 Investigators. Apixaban versus enoxaparin for thromboprophylaxis after hip replacement. N Engl J Med. 2010;363(26): 2487-2498.
16. 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(9717):807-815.
17. Raskob G, Cohen AT, Eriksson BI, et al. Oral direct factor Xa inhibition with edoxaban for thromboprophylaxis after elective total hip replacement. A randomised double-blind dose-response study. Thromb Haemost. 2010;104(3):642-649.
18. Fuji T, Fujita S, Tachibana S, Kawai Y. A dose-ranging study evaluating the oral factor Xa inhibitor edoxaban for the prevention of venous thromboembolism in patients undergoing total knee arthroplasty. J Thromb Haemost. 2010;8(11):2458-2468.
19. Luettgen JM, Bozarth TA, Bozarth JM, et al. In vitro evaluation of apixaban, a novel, potent, selective and orally bioavailable factor Xa inhibitor [abstract no 4130]. Presented at ASH 2006. Blood (ASH Annual Meeting Abstracts). November 16, 2006;108(11).
20. Jiang X, Crain EJ, Luettgen JM, Schumacher WA, Wong PC. Apixaban, an oral direct factor Xa inhibitor, inhibits human clot-bound factor Xa activity in vitro. Thromb Haemost. 2009;101(4):780-782.
21. He K, He B, Grace JE, et al. Preclinical pharmacokinetic and metabolism of apixaban, a potent and selective factor Xa inhibitor [abstract no 910]. Presented at ASH. Blood (ASH Annual Meeting Abstracts). November 16, 2006;108(11).
22. Frost C, Yu Z, Nepal S, et al. Apixaban, a direct factor Xa inhibitor: single-dose pharmacokinetics and pharmacodynamics of an intravenous formulation [abstract no 142]. J Clin Pharmacol. 2008;48(9):1132.
23. Frost C, Yu Z, Moore K, et al. Apixaban, an oral direct factor Xa inhibitor: multiple-dose safety, pharacokinetics, and pharmacodynamics in healthy subjects [abstract no PM-664]. Prestented at ISTH 2007. J Thromb Haemost. 2007;5(Suppl 2):P-M-664.
24. 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.
25. Morishima Y, Furugohri T, Isobe K, et al. In vitro characteristics, anticoagulant effects and in vivo antithrombotic efficacy of a novel, potent and orally active direct factor Xa inhibitor, DU-176b [abstract no 1862]. Presented at ASH 2004. Blood (ASH Annual Meeting Abstracts). November 16, 2004;104(11).
26. Shibano T, Tsuji N, Kito F, et al. Effects of DU-176b, a novel direct factor Xa inhibitor, on prothrombinase activity and platelet aggregation in vitro [abstract no PT-642]. Presented at ISTH 2007. J Thromb Haemost. 2007;5(Suppl 2): P-T-642.
27. 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.
28. Weinz C, Radtke M, Schmeer K, et al. In vitro metabolism of BAY 59-7939 -an oral, direct factor Xa inhibitor [abstract no 195]. Drug Metab Rev. 2004;36(Suppl 1):98.
29. Gross PL, Weitz JI. New anticoagulants for treatment of venous thromboembolism. Arterioscler Thromb Vasc Biol. 2008;28(3): 380-386.
30. Weinz C, Schwartz T, Pleiss U, et al. Metabolism and distribution of [14C]BAY 59-7939 -an oral, direct factor Xa inhibitor -in rat, dog and human [abstract no 196]. Drug Metab Rev. 2004;36(Suppl 1):98.
31. Laux V, Perzborn E, Kubitza D, Misselwitz F, et al. Preclinical and clinical characteristics of rivaroxaban: a novel, oral, direct factor Xa inhibitor. Semin Thromb Hemost. 2007;33(5):515-523.
32. Rautio J, Humphreys JE, Webster LO, et al. In vitro p-glycoprotein inhibition assays for assessment of clinical drug interaction potential of new drug candidates: a recommendation for probe substrates. Drug Metab Dispos. 2006;34(5):786-792.
33. 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.
34. 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.
35. Bayer-Inc. Xarelto® (rivaroxaban 10 mg tablets): product monograph [online].
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. Furugohri T, Isobe K, Honda Y, et al. Pharmacological characterization, antithrombotic and bleeding effects of DU-176b, a novel, potent and orally active direct inhibitor of factor Xa: a wider safety margin of antithrombotic and bleeding effects compared to heparin, LMWH and warfarin [abstract no P1110]. Presented at ISTH; 2005.
38. 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(4):883-888.
39. Ayyub MA, El-Moursy SA, Khazindar AM, Abbas FA. Successful treatment of chronic hepatitis C virus infection with peginterferon alpha-2a and ribavirin in patients with sickle cell disease. Saudi Med J. 2009;30(5):712-716.
40. Ruff CT, Giugliano RP, Antman EM, 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. 160(4):635-641.
41. Masumoto H, Yoshigae Y, Watanabe K, et al. In vitro metabolism of edoxaban and the enzymes involved in the oxidative metabolism of edoxaban [abstract]. AAPS J. 2010;12(S2):W4308.
42. Stangier J. Clinical pharmacokinetics and pharmacodynamics of the oral direct thrombin inhibitor dabigatran etexilate. Clin Pharmacokinet. 2008;47(5):285-295.
43. Lassen MR, Davidson BL, Gallus A, Pineo G, Ansell J, Deitchman D. The efficacy and safety of apixaban, an oral, direct factor Xa inhibitor, as thromboprophylaxis in patients following total knee replacement. J Thromb Haemost. 2007;5(12):2368-2375.
44. Kwong LM, Muntz JE. Thromboprophylaxis dosing: the relationship between timing of first administration, efficacy, and safety. Am J Orthop (Belle Mead NJ). 2002;31(Suppl 11):16-20.
45. Falck-Ytter Y, Francis CW, Johanson NA, et al. Prevention of VTE in orthopedic surgery patients: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(Suppl 2):e278S-e325S.
46. Barrett YC, Wang Z, Frost C, Shenker A. Clinical laboratory measurement of direct factor Xa inhibitors: anti-Xa assay is preferable to prothrombin time assay. Thromb Haemost. 2010;104(6): 1263-1271.
47. Ogata K, Mendell-Harary J, Tachibana M, et al. Clinical safety, tolerability, pharmacokinetics, and pharmacodynamics of the novel factor Xa inhibitor edoxaban in healthy volunteers. J Clin Pharmacol. 2010;50(7):743-753.
48. Karst A, Bakowski-Enzian B, Perzborn E. Monitoring of rivaroxaban: suitability of a well-established chromogenic anti-Factor Xa assay. J Thromb Haemost. 2009;7(Suppl 2):372.
49. Samama MM, Le Flem L, Guinet C, et al. Suitability of chromogenic anti-FXa methods to measure rivaroxaban in human plasma. J Thromb Haemost. 2009;7(Suppl 2):693.
50. Samama M, Amiral J, Guinet C, et al. Specific and rapid measurement of rivaroxaban in plasma using a new, dedicated chromogenic assay. Haemostaseologie. 2010;30:A37.
51. Becker RC, Yang H, Barrett Y, et al. Chromogenic laboratory assays to measure the factor Xa-inhibiting properties of apixaban -an oral, direct and selective factor Xa inhibitor. J Thromb Thrombolysis. 2011;32(2): 183-187.
52. Lindahl TL, Baghaei F, Blixter IF, et al; Expert Group on Coagulation of the External Quality Assurance in Laboratory Medicine in Sweden. Effects of the oral, direct thrombin inhibitor dabigatran on five common coagulation assays. Thromb Haemost. 2011;105(2):371-378.
53. Stangier J, Feuring M. Using the HEMOCLOT direct thrombin inhibitor assay to determine plasma concentrations of dabigatran. Blood Coagul Fibrinolysis. 2012;23(2):138-143.
54. Turpie AG, Fisher WD, Bauer KA, et al; OdiXa-Knee Study Group. BAY 59-7939: an oral, direct factor Xa inhibitor for the prevention of venous thromboembolism in patients after total knee replacement. A phase II dose-ranging study. J Thromb Haemost. 2005;3(11):2479-2486.
55. Eriksson BI, Dahl OE, Büller HR, et al; BISTRO II Study Group. 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.
56. Eriksson BI, Borris LC, Dahl OE, et al; ODIXa-HIP Study Investigators. A: a once-daily, oral, direct Factor Xa inhibitor, rivaroxaban (BAY 59-7939), for thromboprophylaxis after total hip replacement. Circulation. 2006;114(22):2374-2381.
57. Eerenberg ES, Kamphuisen PW, Sijpkens MK, Meijers JC, Buller HR, Levi M. Reversal of rivaroxaban and dabigatran by prothrombin complex concentrate: a randomized, placebo-controlled, crossover study in healthy subjects. Circulation. 2011;124(14):1573-1579.
58. van Ryn J, Stangier J, Haertter S, et al. Dabigatran etexilate -a novel, reversible, oral direct thrombin inhibitor: interpretation of coagulation assays and reversal of anticoagulant activity. Thromb Haemost. 2010; 103(6):1116-1127.