Venous thromboembolism initial treatment: comparison of NOAC phase III trials
| RE-COVER IRE-COVER II | EINSTEIN-DVTEINSTEIN-PE | AMPLIFY | Hokusai-VTE | |
|---|---|---|---|---|
| Comparison | Dabigatran 150 mg bd vs LMWH/warfarin | Rivaroxaban 15 mg bd 21 days, then 20 mg od vs LMWH/warfarin or VKA | Apixaban 10 mg bd 7 days, then 5 mg bd vs LMWH/warfarin | Edoxaban 60 mg od 30 mg od1 vs LMWH/warfarin |
| Patients, n | RE-COVER I: 2,564 RE-COVER II: 2,568 | EINSTEIN-DVT: 3,449 EINSTEIN-PE: 4,832 | 5,400 | 8,292 |
| Study design | Double blind, double dummy | Open-label | Double blind, | Double blind, double dummy |
| Patient age, years | 55.0 (median) | 55.8 (mean) | 57.2 | 55.8 (mean) |
| 54.7 | 57.9 | |||
| Unprovoked VTE, % | NS | 60.964.7 | 89.8 | 65.9 |
| Cancer, % | 4.8 | 7.0 | 2.5 | 9.2 |
| Heparin lead-in | At least 5 days | None | None | At least 5 days |
| Treatment duration | 6 months | Pre-specified3, 6, or 12 months | 6 months | Flexible3–12 months |
| Recurrent VTE or VTE-related death HR (95% CI)* | 1.10 (0.65–1.84) 1.08 (0.64–1.80) | 0.68 (0.44–1.04) 1.12 (0.75–1.68) | 0.84 (0.60–1.18) | 0.89 (0.70–1.13) |
| Major bleeding HR (95% CI)* | 0.82 (0.45–1.48) 0.69 (0.36–1.32) | 0.65 (0.33–1.30) 0.49 (0.31–0.79) | 0.31 (0.17–0.55) | 0.84 (0.59–1.21) |
| Major or clinically relevant non-major bleeding HR (95% CI)* | 0.63 (0.51–0.77) 0.62 (0.45–0.84) | 0.97 (0.76–1.22) 0.90 (0.76–1.07) | 0.44 (0.36–0.55) | 0.81 (0.71–0.94) |
| Intracranial bleeding, % (warfarin/VKA) | 0.1 (0.2) | NS | 0.1 (0.2) | 0.1 (0.4) |
| Gastrointestinal bleeding, % (warfarin/VKA) | 4.0 (2.8) | NS | 0.3 (0.7) | NS |
All comparisons versus LMWH/warfarin or vitamin K antagonist.
↵*Data for apixaban are presented as relative risk (95% CI)
1Dose of 30 mg od in patients with one of CrCl 15–50 mL/min, weight ≤60kg or concomitant treatment with potent P-glycoprotein inhibitors.
bd = twice per day; HR = hazard ratio; LMWH = low molecular weight heparin; NOAC = non-vitamin K oral anticoagulant; NS = not stated; od = once daily; VKA = vitamin K antagonist; VTE = venous thromboembolism