Table 3.
Summary of bleeding outcomes of DOACs from phase 3 clinical trials for the treatment and secondary prevention of VTE [29–33].
| Major bleeding | Clinically relevant bleeding | |||
|---|---|---|---|---|
|
N
(%) |
HR (95% CI) P value |
N(%) | HR (95% CI) P value |
|
| RECOVER I/II | ||||
| Dabigatran 150 mg BIDa | 37 | 0.73 (0.48–1.11) | 136 | 0.62 (0.50–0.76) |
| (n = 2553) | (1.4) | NR | (5.3) | NR |
| Heparin/VKA | 51 | 217 | ||
| (n = 2554) | (2.0) | (8.5) | ||
| EINSTEIN-DVT | ||||
| Rivaroxabanb | 14 | 0.65 (0.33–1.30) | 139 | 0.97 (0.76–1.22) |
| (n = 1718) | (0.8) | 0.21 | (8.1) | 0.77 |
| Heparin/VKA | 20 | 138 | ||
| (n = 1711) | (1.2) | (8.1) | ||
| EINSTEIN-PE | ||||
| Rivaroxabanb | 26 | 0.49 (0.31–0.79) | 249 | 0.90 (0.76–1.07) |
| (n = 2412) | (1.1) | 0.003 | (10.3) | 0.23 |
| Heparin/VKA | 52 | 274 | ||
| (n = 2405) | (2.2) | (11.4) | ||
| AMPLIFY | ||||
| Apixabanc | 15 | 0.31 (0.17–0.55) | 115 | 0.44 (0.36–0.55) |
| (n = 2676) | (0.6) | <0.001 | (4.3) | <0.001 |
| Heparin/VKA | 49 | 261 | ||
| (n = 2689) | (1.8) | (9.7) | ||
| Hokusai-VTE | ||||
| Edoxaban 60 mg QDa,d | 56 | 0.84 (0.59–1.21) | 349 | 0.81 (0.71–0.94) |
| (n = 4118) | (1.4) | 0.35 | (8.5) | 0.004 |
| Heparin/VKA | 66 | 423 | ||
| (n = 4122) | (1.6) | (10.3) | ||
aWith a parenteral anticoagulation lead-in.
b15 mg BID for 3 weeks followed by 20 mg QD.
c10 mg BID for the first 7 days followed by 5 mg BID for 6 months.
d30 mg QD in patients with creatinine clearance 30–50 mL/min or body weight ≤60 kg or receiving concomitant potent P-glycoprotein inhibitors.
AMPLIFY, apixaban for the initial management of pulmonary embolism and deep-vein thrombosis as first-line therapy; BID, twice daily; CI, confidence interval; DOACs, direct-acting oral anticoagulants; DVT, deep-vein thrombosis; HR, hazard ratio; NR, not reported; PE, pulmonary embolism; QD, once daily; VKA, vitamin K antagonist; VTE, venous thromboembolism.