Study details and baseline patient characteristics
| . | Hokusai-VTE . | RE-COVER . | RE-COVER II . | AMPLIFY . | EINSTEIN-DVT . | EINSTEIN-PE . | Combined . | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| . | Edoxaban (n = 4118) . | VKA (n = 4122) . | Dabigatran (n = 1273) . | VKA (n = 1266) . | Dabigatran (n = 1280) . | VKA (n = 1288) . | Apixaban (n = 2691) . | VKA (n = 2704) . | Rivaroxaban (n = 1731) . | VKA (n = 1718) . | Rivaroxaban (n = 2419) . | VKA (n = 2413) . | DOAC (n = 13 512) . | VKA (n = 13 511) . |
| Treatment duration | 3, 6, or 12 mo* | 6 mo | 6 mo | 6 mo | 3, 6 or 12 mo* | 3, 6 or 12 mo* | — | — | ||||||
| Design | Double-blinded | Double-blinded | Double-blinded | Double-blinded | Open-label | Open-label | — | — | ||||||
| Treatment regimen | — | — | ||||||||||||
| Initial treatment | LWMH or UFH for ≥5 d | LWMH or UFH for ≥5 d | LWMH or UFH for ≥5 d | Apixaban 10 mg bid for 7 d | LMWH† or UFH for ≥5 d | Rivaroxaban 15 mg bid for 3 wk | LMWH† for ≥5 d | Rivaroxaban 15 mg bid for 3 wk | LMWH† for ≥5 d | — | — | |||
| Long-term treatment | Edoxaban 60 mg od‡ | Warfarin (INR 2-3) | Dabigatran 150 mg bid | Warfarin (INR 2-3) | Dabigatran 150 mg bid | Warfarin (INR 2-3) | Apixaban 5 mg bid | Warfarin (INR 2-3) | Rivaroxaban 20 mg od | Any VKA (INR 2-3) | Rivaroxaban 20 mg od | Any VKA (INR 2-3) | — | — |
| Mean age (y) | 55.7 | 55.9 | 55.0 | 54.4 | 54.7 | 55.1 | 57.2 | 56.7 | 55.8 | 56.4 | 57.9 | 57.5 | 56.2 | 56.2 |
| Men | 57% | 57% | 58% | 59% | 61% | 60% | 58% | 59% | 57% | 56% | 54% | 52% | 7750 (57%) | 7690 (57%) |
| Index event | ||||||||||||||
| DVT only | 60% | 60% | 69% | 69% | 69% | 68% | 65% | 66% | 99% | 99% | 0% | 0% | 7682 (57%) | 7675 (57%) |
| PE ± DVT | 40% | 40% | 31% | 31% | 31% | 32% | 35% | 34% | 0% | 0% | 100% | 100% | 5792 (43%) | 5797 (43%) |
| Risk factors | ||||||||||||||
| Unprovoked | 66% | 65% | NR | NR | NR | NR | 90% | 90% | 61% | 63% | 65% | 64% | 7750 (71%) | 7760 (71%) |
| Malignancy (at baseline) | 9% | 10% | 5% | 5% | 4% | 4% | 2% | 3% | 7% | 5% | 5% | 5% | 790 (6%) | 775 (6%) |
| Previous VTE | 19% | 18% | 26% | 25% | 19% | 16% | 17% | 15% | 19% | 19% | 19% | 20% | 2612 (19%) | 2489 (18%) |
| TTR in VKA group | — | 64% | — | 60% | — | 57% | — | 60% | — | 58% | — | 63% | — | — |
| Intended treatment duration | ||||||||||||||
| 3 mo | 12% | 13% | 0% | 0% | 0% | 0% | 0% | 0% | 12% | 12% | 5% | 5% | 820 (6%) | 853 (9%) |
| 6 mo | 48% | 47% | 100% | 100% | 100% | 100% | 100% | 100% | 63% | 63% | 57% | 57% | 9686 (72%) | 9663 (72%) |
| 12 mo | 40% | 40% | 0% | 0% | 0% | 0% | 0% | 0% | 25% | 25% | 37% | 37% | 3006 (22%) | 2995 (22%) |
| . | Hokusai-VTE . | RE-COVER . | RE-COVER II . | AMPLIFY . | EINSTEIN-DVT . | EINSTEIN-PE . | Combined . | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| . | Edoxaban (n = 4118) . | VKA (n = 4122) . | Dabigatran (n = 1273) . | VKA (n = 1266) . | Dabigatran (n = 1280) . | VKA (n = 1288) . | Apixaban (n = 2691) . | VKA (n = 2704) . | Rivaroxaban (n = 1731) . | VKA (n = 1718) . | Rivaroxaban (n = 2419) . | VKA (n = 2413) . | DOAC (n = 13 512) . | VKA (n = 13 511) . |
| Treatment duration | 3, 6, or 12 mo* | 6 mo | 6 mo | 6 mo | 3, 6 or 12 mo* | 3, 6 or 12 mo* | — | — | ||||||
| Design | Double-blinded | Double-blinded | Double-blinded | Double-blinded | Open-label | Open-label | — | — | ||||||
| Treatment regimen | — | — | ||||||||||||
| Initial treatment | LWMH or UFH for ≥5 d | LWMH or UFH for ≥5 d | LWMH or UFH for ≥5 d | Apixaban 10 mg bid for 7 d | LMWH† or UFH for ≥5 d | Rivaroxaban 15 mg bid for 3 wk | LMWH† for ≥5 d | Rivaroxaban 15 mg bid for 3 wk | LMWH† for ≥5 d | — | — | |||
| Long-term treatment | Edoxaban 60 mg od‡ | Warfarin (INR 2-3) | Dabigatran 150 mg bid | Warfarin (INR 2-3) | Dabigatran 150 mg bid | Warfarin (INR 2-3) | Apixaban 5 mg bid | Warfarin (INR 2-3) | Rivaroxaban 20 mg od | Any VKA (INR 2-3) | Rivaroxaban 20 mg od | Any VKA (INR 2-3) | — | — |
| Mean age (y) | 55.7 | 55.9 | 55.0 | 54.4 | 54.7 | 55.1 | 57.2 | 56.7 | 55.8 | 56.4 | 57.9 | 57.5 | 56.2 | 56.2 |
| Men | 57% | 57% | 58% | 59% | 61% | 60% | 58% | 59% | 57% | 56% | 54% | 52% | 7750 (57%) | 7690 (57%) |
| Index event | ||||||||||||||
| DVT only | 60% | 60% | 69% | 69% | 69% | 68% | 65% | 66% | 99% | 99% | 0% | 0% | 7682 (57%) | 7675 (57%) |
| PE ± DVT | 40% | 40% | 31% | 31% | 31% | 32% | 35% | 34% | 0% | 0% | 100% | 100% | 5792 (43%) | 5797 (43%) |
| Risk factors | ||||||||||||||
| Unprovoked | 66% | 65% | NR | NR | NR | NR | 90% | 90% | 61% | 63% | 65% | 64% | 7750 (71%) | 7760 (71%) |
| Malignancy (at baseline) | 9% | 10% | 5% | 5% | 4% | 4% | 2% | 3% | 7% | 5% | 5% | 5% | 790 (6%) | 775 (6%) |
| Previous VTE | 19% | 18% | 26% | 25% | 19% | 16% | 17% | 15% | 19% | 19% | 19% | 20% | 2612 (19%) | 2489 (18%) |
| TTR in VKA group | — | 64% | — | 60% | — | 57% | — | 60% | — | 58% | — | 63% | — | — |
| Intended treatment duration | ||||||||||||||
| 3 mo | 12% | 13% | 0% | 0% | 0% | 0% | 0% | 0% | 12% | 12% | 5% | 5% | 820 (6%) | 853 (9%) |
| 6 mo | 48% | 47% | 100% | 100% | 100% | 100% | 100% | 100% | 63% | 63% | 57% | 57% | 9686 (72%) | 9663 (72%) |
| 12 mo | 40% | 40% | 0% | 0% | 0% | 0% | 0% | 0% | 25% | 25% | 37% | 37% | 3006 (22%) | 2995 (22%) |
bid, twice daily; d, day; mo, month(s); od, once daily, UFH, unfractionated heparin; y, year(s).
Treatment duration was left to the discretion of the physician.
Enoxaparin 1 mg/kg twice daily.
An edoxaban dose of 30 mg once daily was administered to patients with a creatinine clearance of 30 to 50 mL per minute, a body weight <60 kg, and in those receiving concomitant treatment with potent P-glycoprotein inhibitors.