New Oral Anticoagulants in Prophylaxis of Venous Thromboembolic Disease in Major Orthopedic Surgery

Author(s): Carlo Rostagno.

Journal Name: Cardiovascular & Hematological Disorders-Drug Targets

Volume 15 , Issue 3 , 2015

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Abstract:

Despite widespread diffusion of pharmacological prophylaxis, deep venous thrombosis (DVT) is still a common cause of morbidity after major orthopedic surgery (total hip replacement - THR- and total knee replacement -TKR).

At present, clear evidence has been provided that pharmacological primary prophylaxis with low molecular weight heparin (LMWH) is associated with a significant decrease in the incidence of venous thromboembolism. The main limitation of LMWH prophylaxis however is the need for parenteral administration with a not negligible drop-out of treatment. Newer oral anticoagulants (NAOs) dabigatran, rivaroxaban, apixiban and edoxaban may be valid alternatives in elective surgery. Several studies have demonstrated the efficacy and safety of NAOs after THR and TKR. The research for new compounds and their antidote is under continuous development Aim of this paper was to review the indications and clinical results of DVT prophylaxis with NAO in patients undergoing major orthopaedic surgery.

Keywords: Dabigratan, doppler ultrasound, enoxaparin, fondaparinux, heparin, orthopaedic surgery, prophylaxis, pulmonary embolism, rivaroxaban, venous thrombosis.

[1]
Cohen, A.T.; Agnelli, G.; Anderson, F.A.; Arcelus, J.I.; Bergqvist, D.; Brecht, J.G.; Greer, I.A.; Heit, J.A.; Hutchinson, J.L.; Kakkar, A.K.; Mottier, D.; Oger, E.; Samama, M.M.; Spannagl, M. VTE Impact Assessment Group in Europe (VITAE). Venous thromboembolism (VTE) in Europe. The number of VTE events and associated morbidity and mortality. Thromb. Haemost., 2007, 98(4), 756-764.
[2]
Nicolaides, A.N.; Breddin, H.K.; Fareed, J.; Goldhaber, S.; Haas, S.; Hull, R.; Kalodiki, T.; Myers, K.; Samama, M.; Sasahara, A. Cardiovascular Disease Educational and Research Trust and the International Union of Angiology. Prevention of venous thromboembolism. International consensus statement. Guidelines compiled in accordance with the scientific evidence. Int. Angiol., 2001, 20, 1-37.
[3]
Geerts, W.H.; Bergqvist, D.; Pineo, G.F.; Heit, J.A.; Samama, C.M.; Lassen, M.R.; Colwell, C.W. American College of Chest Physicians.Prevention of venous thromboembolism: American College of Chest Physicians evidence-based clinical practice guidelines (8th Edition). Chest; , 2008, 133, pp. 381-453.
[4]
White, R.H.; Zhou, H.; Romano, P.S. Incidence of symptomatic venous thromboembolism after different elective or urgent surgical procedures. Thromb. Haemost., 2003, 90, 446-455.
[5]
Dahl, O.E.; Caprini, J.A.; Colwell, C.W.; Frostick, S.P.; Haas, S.; Hull, R.D.; Laporte, S.; Stein, P.D. Fatal vascular outcomes following major orthopedic surgery. Thromb. Haemost., 2005, 93, 860-866.
[6]
Pellegrini, V.D.; Donaldson, C.T.; Farber, D.C.; Lehman, E.B.; Evarts, C.M. The Mark Coventry Award: prevention of readmission for venous thromboembolism after total knee arthroplasty. Clin. Orthop., 2006, (452), 21-27.
[7]
Januel, J.M.; Chwn, G.; Ruffieux, C. Symptomatic in-hospital deep vein thrombosis and pulmonary embolism following hip and knee arthroplasty among patients receiving recommended prophylaxis: a systematic rewiev. JAMA, 2012, 307, 294-303.
[8]
Kakkar, A.K.; Brenner, B.; Dahl, O.E.; Eriksson, B.I.; Mouret, P.; Muntz, J.; Soglian, A.G.; Pap, A.F.; 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(9632), 31-39.
[9]
Bjørnarå, B.T.; Gudmundsen, T.E.; Dahl, O.E. Frequency and timing of clinical venous thromboembolism after major joint surgery. J. Bone Joint Surg. Br., 2006, 88(3), 386-391.
[10]
White, R.H.; Romano, P.S.; Zhou, H.; Rodrigo, J.; Bargar, W. Incidence and time course of thromboembolic outcomes following total hip or knee arthroplasty. Arch. Intern. Med., 1998, 158(14), 1525-1531.
[11]
Januel, J.M.; Chen, G.; Ruffieux, C.; Quan, H.; Douketis, J.D.; Crowther, M.A.; Colin, C.; Ghali, W.A.; Burnand, B. IMECCHI Group. Symptomatic in-hospital deep vein thrombosis and pulmonary embolism following hip and knee arthroplasty among patients receiving recommended prophylaxis. JAMA, 2012, 307, 294-303.
[12]
Eriksson, B.I.; Lassen, M.R. Pentasaccharide iH-FSPI. Duration of prophylaxis against venous thromboembolism with fondaparinux after hip fracture surgery: a multicenter, randomized, placebo controlled, double-blind study. Arch. Intern. Med., 2003, 163(11), 1337-1342.
[13]
Schiff, R.L.; Kahn, S.R.; Shrier, I.; Strulovitch, C.; Hammouda, W.; Cohen, E.; Zukor, D. Identifying Orthopedic Patients at High Risk for Venous Thromboembolism Despite Thromboprophylaxis. Chest, 2005, 128, 3364-3371.
[14]
Lützner, DL.; Kuhlisch, W.E.; Hartmann, A.; Günther, K.P.; Weiss, N.; Beyer-Westendorf, J. Efficacy and safety of venous thromboembolism prophylaxis with fondaparinux or low-molecular weight heparin in a large cohort of consecutive patients undergoing major orthopaedic surgery-findings from the ORTHO-TEP registry. Br. J. Clin. Pharmacol, 2012.Apr 20. .[Epub ahead of print]
[http://dx.doi.org/10.1111/j.1365-2125.2012.04302.x.]
[15]
Eikelboom, J.W.; Quinlan, D.J.; Douketis, J.D. Extended duration prophylaxis against venous thromboembolism after total hip or knee replacement: a meta-analysis of the randomized trials. Lancet, 2001, 358, 9-15.
[16]
Kakkar, A.K.; Davidson, B.L.; Haas, S.K. Compliance with recommended prophylaxis for venous thromboembolism: improving the use and rate of uptake of clinical practice guidelines. J. Thromb. Haemost., 2004, 2, 221-227.
[17]
Friedman, R.J.; Gallus, A.S.; Cushner, F.D.; Fitzgerald, G.; Anderson, F.A., Jr Global Orthopaedic Registry Investigators.Physician compliance with guidelines for deep-vein thrombosis prevention in total hip and knee arthroplasty. Curr. Med. Res. Opin., 2008, 24, 87-97.
[18]
Mann, K.G.; Brummel, K.; Butenas, S. What is all that thrombin for? J. Thromb. Haemost., 2003, 1, 1504-1514.
[19]
Monroe, D.M.; Hoffman, M.; Oliver, J.A.; Roberts, H.R. Platelet activity of high-dose factor VIIa is independent of tissue factor. Br. J. Haematol., 1997, 99, 542-547.
[20]
Husebye, E.E.; Opdahl, H.; Røise, O.; Aspelin, T.; Lyberg, T. Coagulation, fibrinolysis and cytokine responses to intramedullary nailing of the femur: an experimental study in pigs comparing traditional reaming and reaming with a one-step reamer-irrigator-aspirator system., Injury, 2011, 42(7), 630-637. Epub 2010 Jul 22
[http://dx.doi.org/10.1016/j.injury. 2010.06.025.]
[21]
Petrovic, D. The role of vascular endothelial growth factor gene asthe genetic marker of atherothrombotic disorders and in the gene therapy ofcoronary artery disease. Cardiovasc. Hematol. Agents Med. Chem., 2010, 8(1), 47-54.
[22]
Petrovic, D.; Milanez, T.; Kobal, J.; Bregar, D.; Potisk, K.P.; Peterlin, B. Prothrombotic gene polymorphisms and atherothrombotic cerebral infarction. Acta Neurol. Scand., 2003, 108(2), 109-113.
[23]
Fisher, W.D.; Turpie, A.G. Outpatient thromboprophylaxis after hip or knee surgery: discrepancies and concerns. CMAJ, 2008, 178, 1571-1572.
[24]
Stangier, J.; Eriksson, B.I.; Dahl, O.E.; Ahnfelt, L.; Nehmiz, G.; Stähle, H.; Rathgen, K.; Svärd, R. Pharmacokinetic profile of the oral direct thrombin inhibitor dabigatran etexilate in healthy volunteers and patients undergoing total hip replacement. J. Clin. Pharmacol., 2005, 45, 555-563.
[25]
Eriksson, B.I.; Dahl, O.E.; Rosencher, N.; Kurth, A.A.; van Dijk, C.N.; Frostick, S.P.; Prins, M.H.; Hettiarachchi, R.; Hantel, S.; Schnee, J.; Büller, H.R. 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.
[26]
Eriksson, B.I.; Dahl, O.E.; Rosencher, N.; Kurth, A.A.; van Dijk, C.N.; Frostick, S.P.; Prins, M.H.; Hettiarachchi, R.; Hantel, S.; Schnee, J.; Büller, H.R. 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.
[27]
Eriksson, B.I.; Dahl, O.E.; Huo, M.H.; Kurth, A.A.; Hantel, S.; Hermansson, K.; Schnee, J.M.; Friedman, R.J. RE-NOVATE II Study Group. (2011) Oral dabigatran versus enoxaparin for thromboprophylaxis after primary total hip arthroplasty (RE-NOVATE II*). A randomised, double-blind, non-inferiority trial. Thromb. Haemost., 2011, 105(4), 721-729.
[28]
RE-MOBILIZE Writing Committee Oral thrombin inhibitor dabigatran etexilate versus North American enoxaparin regimen for prevention of venous thromboembolism after knee arthroplasty surgery. J. Arthroplasty, 2009, 24, 1-9.
[29]
Lassen, M.R.; Ageno, W.; Borris, L.C.; Lieberman, J.R.; Rosencher, N.; Bandel, T.J.; Misselwitz, F.; Turpie, A.G. RECORD3 Investigators.Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty. N. Engl. J. Med., 2008, 358(26), 2776-2786.
[30]
Gomes-Outes, A.; Terleira-Fernandez, A.I. Suarez.Gea, M.L.; Vargas-Castrillon, E. Dabigatran m rivaroxaban or apixaban versus enoxaparin for thromboprophylaxis after total hip or knee replacement: systematic review, meta-analysis and indirect treatment comparison. BMJ, 2012, 344e3675
[31]
Eriksson, B.I.; Borris, L.C.; Friedman, R.J.; Haas, S.; Huisman, M.V.; Kakkar, A.K.; Bandel, T.J.; 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(26), 2765-2775.
[32]
Lassen, M.R.; Ageno, W.; Borris, L.C.; Lieberman, J.R.; Rosencher, N.; Bandel, T.J.; Misselwitz, F.; Turpie, A.G. RECORD3 Investigators.Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty. N. Engl. J. Med., 2008, 358(26), 2776-2786.
[33]
Turpie, A.G.; Fisher, W.D.; Bauer, K.A. Kwong. L.M.; Irwin, M.W.; Kälebo, P.; Misselwitz, F.; Gent, M. 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.
[34]
Turpie, A.G.; Lassen, M.R.; Davidson, B.L.; Bauer, K.A.; Gent, M.; Kwong, L.M.; Cushner, F.D.; Lotke, P.A.; Berkowitz, S.D.; Bandel, T.J.; Benson, A.; Misselwitz, F.; Fisher, W.D. RECORD4 Investigators.RECORD4 Investigators. Rivaroxaban versus enoxaparin for thromboprophylaxisprophylaxis after total knee arthroplasty (RECORD4): a randomised trial. Lancet, 2009, 373(9676), 1673-1680.
[35]
Dahl, O.E.; Quinlan, D.J.; Bergqvist, D.; Eikelboom, J.W. A critical appraisal of bleeding events reported in venous thromboembolism prevention trials of patients undergoing hip and knee arthroplasty. J. Thromb. Haemost., 2010, 8(9), 1966-1975.
[36]
Hill, J.; Treasure, T. National Clinical Guideline Centre for Acute and Chronic Conditions. Reducing the risk of venous thromboembolism in patients admitted to hospital: summary of NICE guidance. BMJ, 2010, 340, c95.
[37]
Rath, N.K.; Goodson, M.W.; White, S.P.; Forster, M.C. The use of rivaroxaban for chemical thromboprophylaxis following total knee replacement. Knee, 2013, 20(6), 397-400.
[38]
Lassen, M.R.; Raskob, G.E.; Gallus, A.; Pineo, G.; Chen, D.; Portman, R.J. Apixaban or enoxaparin forthromboprophylaxis after knee replacement. N. Engl. J. Med., 2009, 361, 594-604.
[39]
Lassen, M.R.; Raskob, G.E.; Gallus, A.; Pineo, G.; Chen, D.; Hornick, P. Apixaban versus enoxaparin forthromboprophylaxis after knee replacement (ADVANCE-2): a randomised double-blind trial. Lancet, 2010, 375, 807-815.
[40]
Lassen, M.R.; Gallus, A.; Raskob, G.E.; Pineo, G.; Chen, D.; Ramirez, L.M. Apixaban compared with enoxaparin for thromboprophylaxis after hip replacement. N. Engl. J. Med., 2010, 363, 2487-2498.
[41]
Fuji, T.; Wang, C.J.; Fujita, S.; Kawai, Y.; Nakamura, M.; Kimura, T.; Ibusuki, K.; Ushida, H.; Abe, K.; Tachibana, S. Safety and efficacy of edoxaban, an oral factor Xa inhibitor, versus enoxaparin for thromboprophylaxis after total knee arthroplasty: the STARS E-3 trial. Thromb. Res., 2014, 134(6), 1198-1204.
[42]
Fuji, T.; Wang, C.J.; Fujita, S.; Kawai, Y.; Kimura, T.; Tachibana, S. Safety and efficacy of edoxaban, an oral factor xa inhibitor, for thromboprophylaxis after total hip arthroplasty in Japan and Taiwan. J. Arthroplasty, 2014, 29(12), 2439-2446.
[43]
Sasaki, H.; Ishida, K.; Shibanuma, N.; Tei, K.; Tateishi, H.; Toda, A.; Yamashiro, Y.; Matsumoto, T.; Kuroda, R.; Kurosawa, M. Retrospective comparison of three thromboprophylaxis agents, edoxaban, fondaparinux and enoxaparin for preventing venous thromboembolism in total hip arthroplasty. Int. Orthop., 2014, 38, 525-529.
[44]
Grottke, O.; Honickel, M.; van Ryn, J.; Ten Cate, H.; Rossaint, R.; Spronk, H.M. Idarucizumab, a Specific Dabigatran Reversal Agent, Reduces Blood Loss in a Porcine Model of Trauma With Dabigatran Anticoagulation. J. Am. Coll. Cardiol., 2015, 66(13), 1518-1519.
[45]
Glund, S.; Stangier, J.; Schmohl, M.; Gansser, D.; Norris, S.; van Ryn, J.; Lang, B.; Ramael, S.; Moschetti, V.; Gruenenfelder, F.; Reilly, P.; Kreuzer, J. Safety, tolerability, and efficacy of idarucizumab for the reversal of the anticoagulant effect of dabigatran in healthy male volunteers: a randomised, placebo-controlled, double-blind phase 1 trial. Lancet, 2015, 386(9994), 680-690.
[46]
Ansell, J.E. Universal, class-specific and drug-specific reversal agents for the new oral anticoagulants. J. Thromb. Thrombolysis, 2015. Oct 8.[Epub ahead of print].
[47]
Eerenberg, E.S. Kamphuisen. P.W.; Sijpkens, J.; Meijers, J.C.; Buller, H.R.; Levi, M. Reversal of Rivaroxaban and Dabigatran by Prothrombin Complex Concentrate A Randomized, Placebo-Controlled, Crossover Study in Healthy Subjects. Circulation, 2011, 124, 1573-1579.
[48]
Rodgers, G.M. Prothrombin complex concentrates in emergency bleeding disorders. Am. J. Hematol., 2012, 87, 898-902.
[49]
Kaatz, S.; Kouides, P.A.; Garcia, D.A. Guidance on the emergent reversal of oral thrombin and factor Xa inhibitors. Am. J. Hematol., 2012, 87(1), S141-S145.
[50]
Levi, M.; Levy, J.H.; Andersen, H.F.; Truloff, D. Safety of recombinant activated factor VII in randomized clinical trials. N. Engl. J. Med., 2010, 363, 1791-1800.
[51]
Gruppo di lavoro per le linee guida sul tromboembolismo venoso della Società Italiana per lo Studio dell’Emostasi e della Trombosi. Linee guida per la diagnosi, la profilassi e la terapia del tromboembolismo venoso. Haematologica, 2003, 88(S18), 28-46.
[52]
Falck-Ytter, Y.; Francis, C.W.; Johanson, N.A.; Curley, C.; Dahl, O.E.; Schulman, S.; Ortel, T.L.; Pauker, S.G.; Colwell, C.W. Jr.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, pp. (2)e278S-e325S.


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VOLUME: 15
ISSUE: 3
Year: 2015
Page: [204 - 209]
Pages: 6
DOI: 10.2174/1871529X16666160101122632
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