Table 2.
Efficacy and safety outcomes of NOACs vs standard therapy in Phase III clinical trials for the treatment of acute VTE
| Dabigatran | Rivaroxaban | Apixaban | Edoxaban | |||
|---|---|---|---|---|---|---|
|
| ||||||
| RE-COVER20 | RE-COVER II21 | EINSTEIN DVT16 | EINSTEIN PE17 | AMPLIFY18 | Hokusai-VTE19 | |
| Anticoagulant regimen | 150 mg bid after parenteral agent for 8–11 days | 150 mg bid after parenteral agent for 5–11 days | 15 mg bid for 21 days followed by 20 mg od | 15 mg bid for 21 days followed by 20 mg od | 10 mg bid for 7 days followed by 5 mg bid | 60 mg oda after heparin for a median of 7 days |
| Comparator arm | Parenteral agent/warfarin | Parenteral agent/warfarin | Enoxaparin/VKA | Enoxaparin/VKA | Enoxaparin/warfarin | Heparin/warfarin |
| Treatment duration (months) | 6 | 6 | 3, 6, or 12 | 3, 6, or 12 | 6 | 3–12 |
| Primary efficacy outcome | ||||||
| NOAC vs comparator (%) | 2.4 vs 2.1 | 2.3 vs 2.2 | 2.1 vs 3.0 | 2.1 vs 1.8 | 2.3 vs 2.7 | 3.2 vs 3.5 |
| HR/RR (95% CI) | HR 1.10 (0.65–1.84) | HR 1.08 (0.64–1.80) | HR 0.68 (0.44–1.04) | HR 1.12 (0.75–1.68) | RR 0.84 (0.60–1.18) | HR 0.89 (0.70–1.13) |
| P-value | P<0.001 for non-inferiority | P<0.001 for non-inferiority | P<0.001 for non-inferiority | P=0.003 for non-inferiority | P<0.001 for non-inferiority | P<0.001 for non-inferiority |
| Major bleeding | ||||||
| NOAC vs comparator (%) | 1.6 vs 1.9 | 1.2 vs 1.7 | 0.8 vs 1.2 | 1.1 vs 2.2 | 0.6 vs 1.8 | 1.4 vs 1.6 |
| HR/RR (95% CI) | HR 0.82 (0.45–1.48) | HR 0.69 (0.36–1.32) | HR 0.65 (0.33–1.30) | HR 0.49 (0.31–10.79) | RR 0.31 (0.17–0.55) | HR 0.84 (0.59–1.21) |
| P-value | NA | NA | P=0.21 | P=0.003 | P<0.001 | P=0.35 |
| Major or nonmajor clinically relevant bleeding | ||||||
| NOAC vs comparator (%) | 5.6 vs 8.8 | 5.0 vs 7.9 | 8.1 vs 8.1 | 10.3 vs 11.4 | 4.3 vs 9.7 | 8.5 vs 10.3 |
| HR/RR (95% CI) | HR 0.63 (0.47–0.84) | HR 0.62 (0.45–0.84) | HR 0.97 (0.76–1.22) | HR 0.90 (0.76–1.07) | RR 0.44 (0.36–0.55) | HR 0.81 (0.71–0.94) |
| P-value | P=0.002 | NA | P=0.77 | P=0.23 | P<0.001 | P=0.004 |
Notes:
a
30 mg od in patients with CrCl 30–50 mL/min, body weight ≤60 kg, or receiving concomitant treatment with a potent P-gp inhibitor.
Abbreviations: bid, twice daily; CI, confidence interval; CrCl, creatinine clearance; HR, hazard ratio; NA, not available; NOAC, non-vitamin K antagonist oral anticoagulant; od, once daily; P-gp, P-glycoprotein; RR, relative risk; VKA, vitamin K antagonist; VTE, venous thromboembolism.