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Apixaban

A Review of its Use in the Prevention of Venous Thromboembolism After Knee or Hip Replacement Surgery

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Abstract

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 non-inferiority 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.

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    Emma D. Deeks

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Correspondence to Emma D. Deeks.

Additional information

Various sections of the manuscript reviewed by: T.L. Carman, Harrington Heart and Vascular Institute, University Hospitals Case Medical Center, Cleveland, OH, USA; W.D. Fisher, Department of Surgery, McGill University Health Centre, Montreal, QC, Canada; J. Harenberg, Department of Clinical Pharmacology, Medical Faculty, Ruprecht-Karls-University Heidelberg, Mannheim, Germany; M.R. Lassen, Center of Excellence for Spine Disease, Glostrup Hospital, University of Copenhagen, Glostrup, Denmark; J.A. Paramo Fernandez, Laboratory of Atherosclerosis, Area of Cardiovascular Sciences, Hematology and Hemotherapy Service, Center for Applied Medical Research, Pamplona Navarra University Clinic, Pamplona, Spain; A.G.G. Turpie, Hamilton Health Sciences, McMaster University, Hamilton, ON, Canada.

Data Selection

Sources:Medical literature (including published and unpublished data) on ‘apixaban’ was identified by searching databases (including MEDLINE and EMBASE) for articles published since 1996, bibliographies from published literature, clinical trial registries/databases and websites (including those of regional regulatory agencies and the manufacturer). Additional information (including contributory unpublished data) was also requested from the company developing the drug.

Search strategy: MEDLINE and EMBASE search terms were ‘apixaban’ and (‘venous thromboembolism’ or ‘thromboembolism’ or ‘venous thrombosis’ or ‘deep vein thrombosis’ or ‘thromboprophylaxis and surgery’ or ‘arthroplasty, replacement, hip’ or ‘hip replacement’ or ‘hip arthroplasty’ or ‘arthroplasty, replacement, knee’ or ‘knee replacement’ or ‘knee arthroplasty’ or ‘arthroplasty’ or ‘orthopaedic surgery’ or ‘orthopedic surgery’ or ‘orthopaedics’ or ‘orthopedics’). Searches were last updated 14 May 2012.

Selection: Studies in patients undergoing major orthopaedic surgery who received apixaban. Inclusion of studies was based mainly on the methods section of the trials. When available, large, well controlled trials with appropriate statistical methodology were preferred. Relevant pharmacodynamic and pharmacokinetic data are also included.

Index terms: Apixaban, venous thromboembolism, deep vein thrombosis, pulmonary embolism, pharmacodynamics, pharmacokinetics, therapeutic use, tolerability.

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Deeks, E.D. Apixaban. Drugs 72, 1271–1291 (2012). https://doi.org/10.2165/11209020-000000000-00000

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