New antithrombotic drugs in the prophylaxis of postoperative venous thromboembolism

Czech version

Authors: P. Kessler
Authors‘ workplace: Odd. hematologie a transfuziologie, Nemocnice Pelhřimov, p. o.
Published in: Kardiol Rev Int Med 2012, 14(2): 93-96

Overview

The risk of postoperative venous thromboembolism is substantial, especially in patients undergoing major orthopedic surgery. Low molecular weight heparins have been established as “gold standard” of pharmacological thromboprophylaxis in this group of patients; however, the subcutaneous administration is inconvenient, the effectiveness is dependent on antithrombin level, and they are contraindicated in some cases such as allergy or heparin induced thrombocytopenia. Three new oral anticoagulants have recently been approved for thromboprophylaxis after hip and knee athroplasty – an oral direct thrombin inhibitor dabigatran and two oral direct inhibitors of activated factor X (rivaroxaban and apixaban). Their major benefits are the oral route of administration, relatively wide therapeutic window, and predictable pharmacokinetics. Their major disadvantages are: lack of antidote and contraindication in patients with impairment of renal function (Dabigatran is contraindicated in patients with glomerular filtration < 30 ml/min., rivaroxaban and apixaban are contraindicated in patients with glomerular filtration < 15 ml/min.). The pharmacokinetics of these antithrombotic drugs leads to a low risk of drug interactions; they are limited to P-glycoprotein inhibitors and inducers, which influence the level of dabigatran, drugs inhibiting both P-glycoprotein and CyP 3A4, which increase rivaroxaban and apixaban exposure, and inducers of P-glycoprotein and/or CyP 3A4, which induce reduction of rivaroxaban and apixaban level.

Keywords:
dabigatran – rivaroxaban – apixaban – thromboprophylaxis – hip replacement – knee replacement

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