Apixaban: a review of its use in the prevention of venous thromboembolism after knee or hip replacement surgery.

Apixaban (Eliquis™) is an orally active and selective direct inhibitor of factor Xa indicated for twice-daily use in the EU for the prevention of venous thromboembolism (VTE) in adults who have had knee or hip replacement surgery. In this article, the pharmacological, clinical efficacy and tolerability data relevant to the use of apixaban in this indication are reviewed. Oral apixaban is a generally effective and well tolerated thromboprophylactic agent for use after major orthopaedic surgery. In the large, randomized, double-blind, phase III, noninferiority trials known as ADVANCE-2 and -3, apixaban 2.5 mg twice daily initiated after surgery was generally more effective in preventing VTE in patients undergoing knee or hip replacement surgery than subcutaneous enoxaparin sodium initiated before surgery at the EU recommended dosage of 40 mg once daily, with apixaban conferring this benefit without significantly increasing the risk of bleeding. However, when the same apixaban regimen was compared with the US recommended dosage regimen of subcutaneous enoxaparin sodium (30 mg twice daily, initiated after surgery) in patients undergoing knee replacement surgery in the similarly designed ADVANCE-1 trial, the thromboprophylactic efficacy of apixaban did not meet primary endpoint noninferiority criteria, although apixaban was associated with fewer major or clinically relevant nonmajor bleeds (composite endpoint) than this enoxaparin sodium regimen. Additional comparative efficacy and tolerability data are required to definitively position apixaban with respect to other anticoagulants, including rivaroxaban and dabigatran etexilate. In the meantime, currently available clinical data indicate that apixaban is an emerging option for the prevention of VTE in patients undergoing knee or hip replacement surgery.