Comparing anticoagulants to prevent venous thromboembolism after hip and knee arthroplasty

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Fondaparinux and rivaroxaban were associated with increased risk of major bleeding, and apixaban was superior to enoxaparin in efficacy and safety.
Fondaparinux and rivaroxaban were associated with increased risk of major bleeding, and apixaban was superior to enoxaparin in efficacy and safety.

Fondaparinux, rivaroxaban, and apixaban have a higher efficacy of reducing venous thromboembolism after total hip or knee arthroplasty, but fondaparinux and rivaroxaban are associated with an increased risk of major bleeding, according to data from a meta-analysis published in Acta Orthopaedica.

Min Hur, from the Department of Anesthesiology and Pain Medicine at Seoul National University Hospital in Seoul, South Korea, and colleagues conducted the network meta-analysis comparing 6 anticoagulants used to prevent venous thromboembolism after total hip or knee arthroplasty. The anticoagulants included in the meta-analysis were fondaparinux, dabigatran, rivaroxaban, apixaban, edoxaban, and enoxaparin.

Nineteen double-blind clinical trials were included in the analysis, totaling 43,838 participants. Of these, 47% received enoxaparin, 8% received fondaparinux, 14% received apixaban, 15% received dabigatran, 15% received rivaroxaban, and 1.5% used edoxaban. The researchers performed 2 network analyses to analyze the effect of various enoxaparin dose regimen groups. The first analysis included 2 enoxaparin dose groups and did not include studies of edoxaban, while the second analysis included the studies of edoxaban, along with an “enoxaparin various dose group.”

In the first analysis, the researchers found that patients who were treated with fondaparinux 2.5 mg once daily and rivaroxaban 10 mg once daily had a reduced risk of venous thromboembolism compared with those treated with enoxaparin 40 mg once daily or enoxaparin 30 mg twice daily. Apixaban 2.5 mg twice daily significantly decreased the incidence of venous thromboembolism compared with enoxaparin 40 mg once daily, but not enoxaparin 30 mg twice daily.

They also found that fondaparinux and rivaroxaban increased bleeding compared with enoxaparin 40 mg once daily.  However, fondaparinux, rivaroxaban, and apixaban did not increase bleeding compared with enoxaparin 30 mg twice daily. Apixaban was associated with decreased major bleeding compared with enoxaparin 30 mg twice daily and compared with 40 mg once daily.

In the second analysis, the researchers found that edoxaban significantly decreased the incidence of venous thromboembolism and did not increase major bleeding compared with various doses of enoxaparin.

“Our results also suggest that the bleeding risk of new oral anticoagulants may differ depending on the dose regimen of enoxaparin,” the study authors noted. “However, our results were limited by the significant heterogeneity of definition of bleeding outcome, initiation and continuation of drug, and surgery type.”

Reference

Hur M, Park SK, Koo CH, et al. Comparative efficacy and safety of anticoagulants for prevention of venous thromboembolism after hip and knee arthroplasty: A network meta-analysis. Acta Orthopaedica. 2017 Aug 8. doi:10.1080/17453674.2017.1361131

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