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

Figures

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  Figure 1. Observed and estimated incidence (%) of major VTE for enoxaparin in all active‐ and placebo‐controlled trials included in the analysis. Symbols and horizontal lines represent observed incidence and 95% CI for each unique treatment group, and vertical lines represent model‐based estimates for THR (blue) and TKR (red). Note that the dose (y) axis is not linear and the axis labels serve to group the studies by dose (10, 20, 40, and 60 mg per day). Panel a shows model‐based estimates and observations of absolute incidence for each dose in each individual trial. Panel b shows the model‐estimated and observed odds ratio vs. the predicted placebo response for each trial. CI, confidence interval; THR, total hip replacement; TKR, total knee replacement; VTE, venous thromboembolism.

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  Figure 2. Observed and estimated incidence (%) of major bleeding for enoxaparin in all active‐ and placebo‐controlled trials included in the analysis. Symbols and horizontal lines represent observed incidence and 95% CI for each unique treatment group, and vertical lines represent model‐based estimates for THR (blue) and TKR (red). Note that the dose (y) axis is not linear and the axis labels serve to group the studies by dose (10, 20, 40, and 60, mg per day). Panel a shows model‐based estimates and observations of absolute incidence for each dose in each individual trial. Panel b shows the model‐estimated and observed odds ratio vs. the predicted placebo response for each trial. CI, confidence interval; THR, total hip replacement; TKR, total knee replacement.

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  Figure 3. Observed and estimated odds ratio vs. control for major VTE (panel a) and total VTE (panel b) for all trials that evaluated apixaban, edoxaban, rivaroxaban, and dabigatran at their approved doses. The symbols represent the observed odds ratio, the horizontal lines represent 95% CI on the observed odds ratio, and the vertical lines indicate the model estimates. CI, confidence interval; VTE, venous thromboembolism.

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  Figure 4. Observed and estimated odds ratio vs. control for major bleeding (panel a) and clinically relevant bleeding (panel b) for all trials that evaluated apixaban, edoxaban, rivaroxaban, and dabigatran at their approved doses. The symbols represent the observed odds ratio, the horizontal lines represent 95% CI on the observed odds ratio, and the vertical lines indicate the model estimates. CI, confidence interval.

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  Figure 5. Estimated dose–response relationships of the odds ratio vs. 40 mg q.d. (panel a) and 30 mg Q12H (panel b) enoxaparin for major VTE and major bleeding for apixaban, edoxaban, rivaroxaban, and dabigatran. The solid lines are the model estimates and the dashed lines indicate the 90% CI. CI, confidence interval; Q12H, every 12 h; q.d., once daily; VTE, venous thromboembolism.