Comparative efficacy and safety of anticoagulants for prevention of venous thromboembolism after hip and knee arthroplasty

Abstract

Background and purpose - New oral anticoagulants have been developed to prevent venous thromboembolism (VTE) after knee or hip arthroplasty. Although there have been several network meta-analyses (NMA) to compare different regimens, an NMA including 2 different enoxaparin doses and edoxaban has not been performed. Methods - Standard NMA for fondaparinux, dabigatran, rivaroxaban, apixaban, edoxaban, and enoxaparin was performed. Outcome variables included a composite of total VTE and major/clinically relevant bleeding. The rank probabilities of each treatment outcome were summarized by the surface under the cumulative ranking curve. Results - Fondaparinux, rivaroxaban, and apixaban were associated with a reduced risk of VTE compared with enoxaparin, while dabigatran was not. None of these 3 drugs increased bleeding compared with enoxaparin 30 mg twice daily. However, fondaparinux and rivaroxaban increased bleeding compared with enoxaparin 40 mg once daily, while apixaban did not. Apixaban was even associated with decreased major/clinically relevant bleeding compared with enoxaparin 30 mg twice daily or 40 mg once daily. When edoxaban was included in the NMA, edoxaban decreased VTE and did not increase bleeding compared with enoxaparin. Interpretation - A higher efficacy of fondaparinux and rivaroxaban compared with enoxaparin was associated with increased bleeding tendency, while apixaban was superior to enoxaparin regarding both efficacy and safety. A clustered ranking plot showed that apixaban might be the most preferred regarding efficacy and safety. However, our results were driven by indirect statistical inference and were limited by the heterogeneity of the bleeding outcome definitions, drug initiation and continuation, and different surgery types.

Figure 3.

Network plots of anticoagulants depicted according to the 2 outcomes of venous thromboembolism and major/clinically relevant non-major bleeding. The upper row shows the first analysis set including 2 enoxaparin dose groups and excluding edoxaban. The lower row shows the second analysis set including 1 enoxaparin dose group and including edoxaban. Nodes are weighted according to the number of patients with the respective interventions. Edges are weighted according to the number of studies between the 2 connected modalities.

Figure 4.

Clustered ranking plots of the anticoagulant network based on the analysis of the surface under the cumulative ranking curve (SUCRA) values for venous thromboembolism (X-axis) and a composite of major/clinically relevant non-major bleeding (Y-axis). Each dot was located according to the 2 SUCRA values of each drug for the 2 outcomes. The larger SUCRA values mean the better the rank of the drug. The drug located in the right upper corner has higher SUCRA values for both variables of the X and Y axes and is regarded as the most preferred of the drugs compared. Left and right panels correspond to first and second analysis set, respectively.