Rivaroxaban for venous thromboembolism prevention after major orthopedic surgery: translating trial data into routine clinical practice

Abstract

An established standard of care for the prevention of venous thromboembolism after major orthopedic surgery has been subcutaneous low-molecular-weight heparin. The non-vitamin K antagonist oral anticoagulant rivaroxaban has demonstrated superior efficacy and similar safety to all tested regimens of enoxaparin in large Phase III clinical studies of venous thromboembolism prevention after elective hip and knee arthroplasty. Despite regulatory approval of rivaroxaban for this indication, concerns remain among physicians regarding its optimal and effective use in routine clinical practice. Real-life studies, such as XAMOS and ORTHO-TEP, are providing physicians with more information on the routine use of rivaroxaban for venous thromboembolism prevention after orthopedic surgery, helping to establish its safety and effectiveness in everyday clinical care. Among the most important issues are the risk of bleeding complications, wound healing, timing of first dose, impact of type of anesthesia on thromboprophylaxis effectiveness, patient comorbidities and comedication use, periprocedural management, associated costs, and clinical outcomes in trauma-related fractures. Many of these issues are difficult to study in randomized, double-blind, Phase III trials, and can be assessed more readily using real-life data. In particular, real-life or noninterventional studies lack many of the strict inclusion and exclusion criteria associated with Phase III trials and involve unselected patients who often present with significant comorbidities or comedication use.

Keywords: anticoagulants; arthroplasty; orthopedics; rivaroxaban; thrombosis.

Figure 1

Kaplan–Meier analysis of length of hospital stay with rivaroxaban and fondaparinux. Notes: Subgroups of patients without complications (A), with and without VTE (B), with and without major bleeding (C), and with and without surgical revisions (D). Owing to the interference of complications and confounding factors over time, these analyses are of a descriptive nature only, and were not assessed for statistical significance. Adapted with permission from the Journal of Thrombosis and Haemostasis (John Wiley & Sons Ltd, Chichester, UK). Beyer-Westendorf J, Lützner J, Donath L, et al. Efficacy and safety of rivaroxaban or fondaparinux thromboprophylaxis in major orthopedic surgery: findings from the ORTHO-TEP registry. 2012;10(10):2045–2052. © 2012 International Society on Thrombosis and Haemostasis. Abbreviations: CI, confidence interval; VTE, venous thromboembolism.

Figure 2

Kaplan–Meier analysis of length of hospital stay with rivaroxaban and LMWH. Notes: Subgroups of patients without complications (A), with and without VTE (B), with and without major bleeding (C), and with and without surgical revisions (D). Owing to the interference of complications and confounding factors over time, these analyses are of a descriptive nature only, and were not assessed for statistical significance. Adapted with permission from the Journal of Thrombosis and Haemostasis (Schattauer Publishers, Stuttgart, Germany). Beyer-Westendorf J, Lützner J, Donath L, et al. Efficacy and safety of thromboprophylaxis with low-molecular-weight heparin or rivaroxaban in hip and knee replacement surgery: findings from the ORTHO-TEP registry. 2013;109(1):154–163. © Schattauer Publishers, Stuttgart. Abbreviations: LMWH, low-molecular-weight heparin; VTE, venous thromboembolism.