Table 1.
Description of characteristics for included trials.
| Study name (year) [reference number] | Population characteristics | Information on Intervention/Control (dosage, administration, duration) | Outcome measure | Follow-up period (months) | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Number of randomized patients | Study arm | Sample size for each arm (% for females) | Age: years | % for patientswith cancer | Time in therapeutic range | % for patient with creatinine clearance <50 ml/min | Efficacy | Safety | |||
| DABIGATRAN (n = 3) | |||||||||||
| RE-COVER I (2009) (15) | 2,539 | DOAC | 1,273 (42%) | 55 | 5% | NA | 5.0% | Dabigatran (150 mg orally twice daily for 6 months) | Venous thromboembolism or related death | Major bleeding event or clinically relevant bleeding | 6 |
| VKA | 1,266 (41%) | 54 | 4.5% | 60.0% | 4.5% | Warfarin (150 mg dose-adjusted for 6 months) | |||||
| RE-MEDY (2013) (17) | 2,856 | DOAC | 1,430 (39%) | 55 | 4.2% | NA | NA | Dabigatran (150 mg orally twice daily for 6 months) | Recurrent symptomatic VTE or VTE mortality | Major bleeding event or clinically relevant bleeding | 36 |
| VKA | 1,426 (39%) | 54 | 4.1% | 65.3% | NA | Warfarin (at a fixed dose of 150 mg twice daily for 6 months) | |||||
| RE-COVER II (2014) (16) | 2,568 | DOAC | 1,280 (39%) | 56 | 3.9% | NA | NA | Dabigatran (150 mg twice daily for 6 months) | Recurrent symptomatic, confirmed VTE and related deaths | Major bleeding | 6 |
| VKA | 1,288 (40%) | 57 | 3.9% | 56.9% | NA | Warfarin (150 mg for 6 months) | |||||
| RIVAROXABAN (n = 6) | |||||||||||
| ODIXa-DVT (2007) (22) | 604 | DOAC | 119 (41%) | 58.5 | NA | NA | NA | Rivaroxaban (10 mg twice daily for 12 weeks) | Proximal deep vein thrombosis, symptomatic PE, or VTE-related death | Major bleeding | 3 |
| 117 (43%) | 57.5 | NA | NA | NA | Rivaroxaban (20 mg twice daily for 12 weeks) | ||||||
| 121 (35%) | 61.4 | NA | NA | NA | Rivaroxaban (30 mg twice daily for 12 weeks) | ||||||
| 121 (38%) | 59.5 | NA | NA | NA | Rivaroxaban (40 mg twice daily for 12 weeks) | ||||||
| LMWH+VKA | 126 (38.9%) | 58.4 | NA | NA | NA | Enoxaparin 1 mg/kg BID followed by VKA for 12 weeks | |||||
| Einstein-DVT Dose-Ranging Study (2008) (23) | 543 | DOAC | 135 (53%) | 58 | 8% | NA | NA | Rivaroxaban (20 mg once daily for 84 days) | Composite of symptomatic venous thromboembolism and asymptomatic deterioration in thrombotic burden | Major bleeding and clinically relevant nonmajor bleeding | 3 |
| 134 (49%) | 57 | 10% | NA | NA | Rivaroxaban (30 mg once daily for 84 days) | ||||||
| 136 (48%) | 60 | 12% | NA | NA | Rivaroxaban (40 mg once daily for 84 days) | ||||||
| LMWH+VKA | 137(47%) | 57 | 7% | NA | NA | Combination of LMWH and VKA | |||||
| EINSTEIN-DVT (2010) (18) | 3,449 | DOAC | 1,731 (43%) | 56 | 6.8% | NA | 6.9% | Rivaroxaban (15 mg twice daily for 3 weeks, then 20 mg daily for 3, 6, or 12 months) | Symptomatic recurrent VTE | Clinically relevant bleeding | 12 |
| LMWH+VKA | 1,718 (44%) | 56 | 5.2% | 57.7% | 7.5% | Enoxaparin followed by a warfarin or acenocoumarol for 3, 6, or 12 months | |||||
| EINSTEIN-PE (2012) (19) | 4,832 | DOAC | 2,419 (46%) | 58 | 4.7% | NA | 8.8% | Rivaroxaban (15 mg twice daily for 3 week, then 20 mg daily for 3, 6, or 12 months) | Symptomatic recurrent VTE | Clinically relevant bleeding | 12 |
| LMWH+VKA | 2,413 (48%) | 58 | 4.5% | 62.7% | 8.0% | Enoxaparin followed by an adjusted-dose VKA for 3, 6, or 12 months | |||||
| MAGELLAN (2013) (20) | 8,101 | DOAC | 4,050 (44%) | 71 | 7.3% | NA | 21.5% | Rivaroxaban (10 mg once daily for 35 days) | Composite of asymptomatic proximal or symptomatic VTE | Composite of major or clinically relevant nonmajor bleeding | 3 |
| LMWH | 4,051 (46%) | 71 | 7.3% | NA | 21.5% | Enoxaparin (subcutaneously 40 mg once daily for 10 days) | |||||
| SELECT-D (2018) (21) | 406 | DOAC | 203 (43%) | 67 | 100% | NA | NA | Rivaroxaban (15 mg twice daily for 3 weeks, then 20 mg once daily for 6 months) | Symptomatic recurrent VTE | Major bleeding and clinically relevant non-major bleeding | 24 |
| UFH | 203 (52%) | 67 | 100% | NA | NA | Dalteparin (200 IU/kg daily during month 1, then 150 IU/kg daily for months 2–6) | |||||
| APIXABAN (n = 5) | |||||||||||
| Botticelli DVT dose-ranging study (2008) (28) | 520 | DOAC | 130 (36%) | 56 | 8.5 | NA | NA | Apixaban (5 mg twice-daily for 84–91 days) | Symptomatic recurrent VTE and asymptomatic deterioration in thrombotic burden | Composite of major and clinically relevant, non-major bleeding | 3 |
| 134 (43%) | 59 | 4.5 | NA | NA | Apixaban (10 mg twice-daily for 84–91 days) | ||||||
| 128 (35%) | 60 | 7.0 | NA | NA | Apixaban (20 mg once-daily for 84–91 days) | ||||||
| LMWH+VKA | 128 (36%) | 59 | 8.6% | NA | NA | LMWH followed by a VKA for 3 months | |||||
| ADOPT (2011) (25) | 6,528 | DOAC | 3,255 (50%) | 67 | 9.6% | NA | NA | Apixaban (2.5 mg twice daily for 30 days) | Composite of death related to VTE, PE, symptomatic DVT, or asymptomatic proximal-leg DVT | Major bleeding or clinically relevant bleeding | 3 |
| LMWH | 3,273 (52%) | 67 | 9.8% | NA | NA | Enoxaparin (subcutaneously 40 mg once daily for 6 to 14 days) | |||||
| AMPLIFY (2013) (24) | 5,395 | DOAC | 2,691 (42%) | 57 | 2.5% | NA | 6.5% | Apixaban (10 mg, twice daily for 7 days, then 5 mg twice daily for 6 months) | Recurrent symptomatic VTE or VTE mortality | Major bleeding | 6 |
| VKA | 2,704 (41%) | 57 | 2.8% | NA | 6.1% | Enoxaparin, followed by warfarin for 6 months | |||||
| AMPLIFY-J Study (2015) (27) | 80 | DOAC | 40 (45%) | 64.3 | NA | NA | 5.0% | Apixaban was initiated at 10 mg twice daily for 7 days, followed by 5 mg twice daily for 23 weeks | Recurrent symptomatic VTE or VTE-related death | Major bleeding | 8 |
| UFH | 40 (57.5%) | 66.1 | NA | 70.1% | 20.0% | Unfractionated heparin (UFH) and warfarin for 24 weeks | |||||
| ADAM VTE Trial (2020) (26) | 300 | DOAC | 150 (52%) | 64.4 | 100% | NA | 9.3% | Apixaban (10 mg twice daily for 7 days followed by 5 mg twice daily for 6 months) | Recurrent VTE or arterial thromboembolism | Major bleeding | 6 |
| UFH | 150 (51.3%) | 64.0 | 100% | NA | 9.3% | Dalteparin (200 IU/Kg daily for 30 days followed by 150 IU/kg for months 2 through 6) | |||||
| EDOXABAN (n = 2) | |||||||||||
| Hokusai-VTE (2013) (29) | 8,240 | DOAC | 4,118 (43%) | 56 | 9.2% | NA | 6.5% | Edoxaban (30 or 60 mg once daily for 3 to 12 months) | Symptomatic recurrent VTE | Clinically relevant bleeding | 12 |
| VKA | 4,122 (43%) | 56 | 9.5% | 63.5% | 6.6% | Warfarin for 12 months | |||||
| Hokusai VTE Cancer (2018) (30) | 1,046 | DOAC | 522 (47%) | 64 | 100% | NA | 7.3% (30–50 mL/min) | Edoxaban (60 mg once daily for 3 to 12 months) | Symptomatic recurrent VTE | Major bleeding | 12 |
| UFH | 524 (50%) | 64 | 100% | NA | 6.5% (30–50 mL/min) | Dalteparin at a dose of 200 IU/kg for 3 to 12 months | |||||