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

Abstract

Background:

Apixaban is a novel oral factor Xa inhibitor that recently completed evaluation in clinical trials for its use in the prevention of venous thromboembolism (VTE) in patients undergoing hip or knee replacement surgery. Its manufacturers are currently seeking approval for these indications in the European Union and a rolling submission is in process in the United States.

Scope:

This article reviews published data on the efficacy and safety profile of apixaban in patients undergoing total knee arthroplasty (TKA). For this review, the authors searched PubMed for English language clinical trial articles involving the use of apixaban in human subjects published through July 11, 2011. The key words ‘apixaban’ and ‘total knee arthroplasty/replacement’ were used. The review focused on clinical trials, but other articles were reviewed for relevant information.

Findings:

One dose-finding phase II trial demonstrated apixaban’s efficacy and a dose of 2.5 mg twice daily was established for future investigation. Two phase III clinical trials have been completed with apixaban in TKA patients (ADVANCE-1 and ADVANCE-2). In ADVANCE-1, apixaban did not meet the pre-specified non-inferiority criteria, while in ADVANCE-2, apixaban met the non-inferiority criteria when compared to enoxaparin, and had a similar safety profile.

Conclusion:

Apixaban is a promising new agent awaiting regulatory approval for its use in thromboprophylaxis after TKA.

Key words::

• Anticoagulant
• Apixaban
• Direct factor Xa inhibitor
• TKA

Transparency

Declaration of funding

No funding was obtained for the writing of this article.

Declaration of financial/other relationships

E.A.N. is supported by the University of Illinois at Chicago (UIC) Center for Clinical and Translational Science (CCTS), Award Number KL2RR029878 from the National Center for Research Resources. The authors do not have any other financial relationships with or employment by the manufacturers of the medications discussed in this article.

CMRO peer reviewer #1 has disclosed that he is on the Speakers’ Bureau of Boerhinger-Ingelheim. Peer reviewer # 2 has disclosed that he has received sponsorship and/or grants from Bayer, BMS, Boerhinger-Ingelheim, Pfizer and Sanofi-Aventis. He has also disclosed that he has been a consultant to Bayer and Portola and is on the Speakers’ Bureau of Bayer.