Direct Oral Anticoagulants Vs. Enoxaparin for Prevention of Venous Thromboembolism Following Orthopedic Surgery: A Dose–Response Meta‐analysis

We carried out a dose–response model‐based meta‐analysis to assess venous thromboembolism (VTE) and bleeding with factor Xa (FXa) inhibitors (apixaban, edoxaban, rivaroxaban) and a thrombin inhibitor (dabigatran) compared with European (EU) (40 mg q.d.) and North American (NA) (30 mg Q12H) dose regimens of a low molecular weight heparin (enoxaparin) following orthopedic surgery. Statistically significant differences in both VTE and bleeding outcomes were found between the NA and EU doses of enoxaparin, with odds ratios (95% confidence interval) for the NA vs. EU dose of 0.73 (0.71–0.76) and 1.20 (1.14–1.29) for total VTE and major bleeding, respectively. At approved doses, estimated odds ratios vs. both doses of enoxaparin for the three FXa inhibitors (range: 0.35–0.75 for VTE; 0.76–1.09 for bleeding) compared with those for dabigatran (range: 0.66–1.21 for VTE; 1.10–1.38 for bleeding) suggested generally greater efficacy and less bleeding for the FXa inhibitors.