Therapeutic potential of apixaban in the prevention of venous thromboembolism in patients undergoing total knee replacement surgery

Anticoagulant prophylaxis for preventing venous thromboembolism (VTE) is a worldwide established procedure in hip and knee replacement surgery. Despite available anticoagulant prophylaxis, patients who undergo total knee arthroplasty (TKA) have a high incidence of venous VTE. In spite of their proven efficacy, the currently available anticoagulants have limitations that driven to develop new oral agents that directly target specific factors in the coagulation cascade, such as direct thrombin inhibitors and direct Factor Xa inhibitors, in an attempt to overcome some of the drawbacks with the traditional agents. Apixaban is a potent, selective direct inhibitor of the coagulation factor Xa, recently approved in Europe for the prevention of venous thromboembolism (VTE) in adult patients after total hip replacement (THR) or total knee replacement (TKR) surgery. Apixaban has been extensively studied worldwide in about 12,000 patients in four clinical studies that have demonstrated the efficacy and safety of apixaban respect to enoxaparin for the prevention of thromboembolism after major orthopedic surgery. Three of these trials involved 7,337 patients who undergo TKR: one phase II trial (APROPOS Study) and two large phase III trials (ADVANCE 1 and ADVANCE 2 Studies). ADVANCE 1 demonstrated that when compared with enoxaparin 30 mg twice daily for efficacy, apixaban did not meet the prespecified statistical criteria for noninferiority, but its use was associated with lower rates of clinically relevant bleeding. ADVANCE 2 showed that apixaban was superior to the European standard dose of enoxaparin of 40 mg once daily in term of efficacy, with a similar incidence of major bleeding. This review focuses the clinical efficacy and tolerability of oral apixaban for the prevention of VTE in adult patients following TKR surgery.