title: 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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Apixaban is a promising new agent awaiting regulatory approval for its use in thromboprophylaxis after TKA.
authors.affiliation: Department of Pharmacy Practice, College of Pharmacy, University of Illinois at Chicago Medical Center, Chicago, IL, USA. mmichell@uic.edu
authors.forename: Michelle T
authors.initials: MT
authors.lastname: Martin
authors.forename: Edith A
authors.initials: EA
authors.lastname: Nutescu
mesh_terms: D000284:Administration, Oral; D000925:Anticoagulants / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D019645:Arthroplasty, Replacement, Knee / Q000009:adverse effects*; D002986:Clinical Trials as Topic; D005062:European Union; D006801:Humans; D011720:Pyrazoles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D011728:Pyridones / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D014481:United States; D054556:Venous Thromboembolism / Q000209:etiology / Q000517:prevention & control*
chemical_list: D000925:Anticoagulants; D011720:Pyrazoles; D011728:Pyridones; C522181:apixaban