Table 3.
Summary of phase III studies of direct oral anticoagulants for long-term prevention of recurrent VTE [4, 10, 11]
| Drug | Study | Indication | Regimen | Dose schedule | Comparator | Efficacy | Safety |
|---|---|---|---|---|---|---|---|
| Rivaroxaban | EINSTEIN EXT | Patients with previous VTE already treated for 6–12 months with anticoagulant therapy | Single drug | 20 mg od for a further 6 or 12 months | Placebo | Recurrent VTE: rivaroxaban superior to placebo (1.3% vs. 7.1%; HR = 0.18; p < 0.001) | Clinically relevant bleeding: greater incidence with rivaroxaban than placebo (6.0% vs. 1.2%; HR = 5.19; p < 0.001) |
| Major bleeding: similar incidence (0.7% vs. 0%; HR N/A; p = 0.11) | |||||||
| Apixaban | AMPLIFY-EXT | Patients with previous VTE already treated for 6–12 months with anticoagulant therapy | Single drug | 2.5 mg or 5 mg bid for a further 12 months | Placebo | Recurrent VTE: apixaban superior to placebo (3.8% and 4.2% vs. 11.6%; RR = 0.33 and 0.36; p < 0.001 for both doses) | Clinically relevant bleeding: similar incidence (3.2% and 4.3% vs. 2.7%; RR = 1.20 and RR = 1.62; p = N/S) |
| Major bleeding: similar incidence (0.2% and 0.1% vs. 0.5%; RR = 0.49 and RR = 0.25; p = N/S) | |||||||
| Dabigatran | RE-SONATE | Patients with previous VTE already treated for at least 3 months with anticoagulant therapy | Single drug | 150 mg bid for a further 6 months | Placebo | Recurrent VTE: dabigatran superior to placebo (0.4% vs. 5.6%; HR = 0.08; p < 0.001) | Clinically relevant bleeding: greater incidence with dabigatran than placebo (5.3% vs. 1.8%; HR = 2.92; p = 0.001) |
| Major bleeding: similar incidence (0.3% vs. 0%; HR N/A; p = 1.0) | |||||||
| Dabigatran | RE-MEDY | Patients with previous VTE already treated for at least 3 months with anticoagulant therapy | Single drug | 150 mg bid for a further 6 months | Warfarin (INR 2.0–3.0) | Recurrent VTE: dabigatran non-inferior to warfarin (1.8% vs. 1.3%; HR = 1.44; p = 0.01 for non-inferiority) | Clinically relevant bleeding: significantly lower incidence with dabigatran vs. warfarin (5.6% vs. 10.2%; HR = 0.54; p < 0.001) |
| Major bleeding: lower incidence with dabigatran but not statistically significant (0.9% vs. 1.8%; HR = 0.52; p = 0.06) |
bid, twice daily; HR, hazard ratio; INR, international normalised ratio; N/A, not applicable; N/S, not specified; od, once daily; RR, relative risk; VTE, venous thromboembolism.