The new oral anticoagulants, do they change the benefit vs. risk for thromboprophylaxis in association to ambulatory surgery?

Purpose of review Several randomized controlled trials have shown that pharmacological thromboprophylaxis with low-dose unfractionated heparin (UFH), low molecular weight heparin (LMWH) or fondaparinux reduces venous thromboembolism (VTE) after general surgery. No high-quality evidence supports the use of pharmacological thromboprohylaxis with traditional antithrombotic drugs in patients undergoing ambulatory surgery without additional VTE risk factors, stratified at low risk of VTE by the American College of Chest Physicians guidelines. Two new drug classes, the direct thrombin and factor Xa (FXa) inhibitors, have been developed with a potentially better risk-benefit profile. Recent findings Oral administration, predictable anticoagulant responses, low potential for drug–drug interactions render direct thrombin and factor Xa inhibitors good candidates to replace UFH, LMWH and fondaparinux for VTE prophylaxis. Most of all, the positive results of the first published clinical trials in orthopedic thromboprophylaxis allowed dabigatran etexilate and rivaroxaban to be licensed in Canada and in European Union for the prevention of VTE in patients undergoing hip-replacement and knee-replacement surgery. Summary No randomized trials with the new anticoagulants are ongoing in ambulatory surgery. However, currently available drugs – that is UFH, LMWH or fondaparinux – are administered subcutaneously and the new anticoagulants would offer the clear advantage of an oral administration, without request for blood testing to monitor potential adverse effects such as heparin-induced thrombocytopenia, thus potentially simplifying the treatment out of the hospital.

[1]  B. Eriksson,et al.  Oral Anticoagulants in Development , 2012, Drugs.

[2]  G. Raskob,et al.  Apixaban versus enoxaparin for thromboprophylaxis after knee replacement (ADVANCE-2): a randomised double-blind trial , 2010, The Lancet.

[3]  G. Raskob,et al.  Apixaban or enoxaparin for thromboprophylaxis after knee replacement. , 2009, The New England journal of medicine.

[4]  M. Gent,et al.  Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty (RECORD4): a randomised trial , 2009, The Lancet.

[5]  B. Eriksson,et al.  Efficacy and safety of dabigatran etexilate for the prevention of venous thromboembolism following total hip or knee arthroplasty , 2008, Thrombosis and Haemostasis.

[6]  G. Raskob,et al.  Oral thrombin inhibitor dabigatran etexilate vs North American enoxaparin regimen for prevention of venous thromboembolism after knee arthroplasty surgery. , 2009, The Journal of arthroplasty.

[7]  B. Eriksson,et al.  Comparative Pharmacodynamics and Pharmacokinetics of Oral Direct Thrombin and Factor Xa Inhibitors in Development , 2009, Clinical pharmacokinetics.

[8]  Bengt I Eriksson,et al.  Extended duration rivaroxaban versus short-term enoxaparin for the prevention of venous thromboembolism after total hip arthroplasty: a double-blind, randomised controlled trial , 2008, The Lancet.

[9]  W. Ageno,et al.  Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty. , 2008, The New England journal of medicine.

[10]  B. Eriksson,et al.  Rivaroxaban versus enoxaparin for thromboprophylaxis after hip arthroplasty. , 2008, The New England journal of medicine.

[11]  J. Hirsh,et al.  New antithrombotic drugs: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). , 2008, Chest.

[12]  P. Lam,et al.  Apixaban, an oral, direct and highly selective factor Xa inhibitor: in vitro, antithrombotic and antihemostatic studies , 2008, Journal of thrombosis and haemostasis : JTH.

[13]  A. Venco,et al.  Thromboprophylaxis in day surgery. , 2008, International journal of surgery.

[14]  S. Frostick,et al.  Oral dabigatran etexilate vs. subcutaneous enoxaparin for the prevention of venous thromboembolism after total knee replacement: the RE‐MODEL randomized trial , 2007, Journal of thrombosis and haemostasis : JTH.

[15]  S. Frostick,et al.  Dabigatran etexilate versus enoxaparin for prevention of venous thromboembolism after total hip replacement: a randomised, double-blind, non-inferiority trial , 2007, The Lancet.

[16]  K. Rathgen,et al.  The pharmacokinetics, pharmacodynamics and tolerability of dabigatran etexilate, a new oral direct thrombin inhibitor, in healthy male subjects. , 2007, British journal of clinical pharmacology.

[17]  A. Turpie Oral, Direct Factor Xa Inhibitors in Development for the Prevention and Treatment of Thromboembolic Diseases , 2007, Arteriosclerosis, thrombosis, and vascular biology.

[18]  D. Kubitza,et al.  Novel factor Xa inhibitors for prevention and treatment of thromboembolic diseases , 2006, Expert opinion on investigational drugs.

[19]  F. Farrokhyar,et al.  Practice patterns for deep vein thrombosis prophylaxis in minimal-access surgery. , 2006, Canadian journal of surgery. Journal canadien de chirurgie.

[20]  B. Eriksson,et al.  Oral anticoagulants in development: focus on thromboprophylaxis in patients undergoing orthopaedic surgery. , 2006, Drugs.

[21]  Michael Becka,et al.  Safety, pharmacodynamics, and pharmacokinetics of BAY 59-7939—an oral, direct Factor Xa inhibitor—after multiple dosing in healthy male subjects , 2005, European Journal of Clinical Pharmacology.

[22]  D. Bergqvist,et al.  Current Options in the Prevention of Thromboembolic Disease , 2004, Drugs.

[23]  Dennis Mungall BIBR-1048 Boehringer Ingelheim. , 2002, Current opinion in investigational drugs.

[24]  D. Hosmer,et al.  A population-based perspective of the hospital incidence and case-fatality rates of deep vein thrombosis and pulmonary embolism. The Worcester DVT Study. , 1991, Archives of internal medicine.

[25]  J W Goodfellow,et al.  Unicompartmental Oxford Meniscal knee arthroplasty. , 1987, The Journal of arthroplasty.