Background
Initial management
Oral anticoagulants
Review
Acute and long-term treatment of venous thromboembolism
Thrombolytic and interventional treatment for acute venous thromboembolism
Outpatient treatment of venous thromboembolism
Vitamin K antagonists versus direct oral anticoagulants
Trial name | RE-COVER | RE-COVER II | EINSTEIN-DVT | EINSTEIN-PE | AMPLIFY | Hokusai-VTE |
---|---|---|---|---|---|---|
Year of Publication [Ref] | 2009 [15] | 2014 [16] | 2010 [17] | 2012 [18] | 2013 [19] | 2013 [20] |
Design | Double-blinded | Double-blinded | PROBE | PROBE | Double-blinded | Double-blinded |
Number of Patients | 2539 | 2589 | 3449 | 4832 | 5395 | 8292 |
Indication for Anticoagulation | Acute VTE | Acute VTE | Acute DVT | Acute PE | Acute VTE | Acute VTE |
DOAC Treatment Protocol | Dabigatran 150 mg twice daily | Dabigatran 150 mg twice daily | Rivaroxaban 15 mg twice daily for 3 weeks; then 20 mg once daily | Rivaroxaban 15 mg twice daily for 3 weeks; then 20 mg once daily | Apixaban 10 mg twice daily for days; then 5 mg twice daily | Edoxaban 60 once daily; patients with CrCl 30–50 mL/min, body weight ≤60 kg, or receiving strong P-glycoprotein inhibitors: edoxaban 30 mg once daily |
Non-inferiority Margin for Hazard Ratio | 2.75 | 2.75 | 2.0 | 2.0 | 1.8 | 1.5 |
Need for initial Parenteral Anticoagulation | Yes | Yes | No | No | No | Yes |
Duration of Therapy (months) | 6 | 6 | 3, 6, or 12 | 3, 6, or 12 | 6 | ≤12 |
TTR (%) | 60 | 57 | 58 | 63 | 61 | 64 |
Trial Name [Ref] | RE-COVER [15] | RE-COVER II [16] | EINSTEIN-DVT [17] | EINSTEIN-PE [18] | AMPLIFY [19] | Hokusai-VTE [20] |
---|---|---|---|---|---|---|
Primary Efficacy Outcome DOAC vs VKA (%) | Recurrent symptomatic VTE or related death: 2.4 vs 2.1a
| Recurrent symptomatic VTE or related mortality: 2.3 vs 2.2a
| Recurrent symptomatic VTE: 2.1 vs 3.0a
| Recurrent symptomatic VTE: 2.1 vs 1.8a
| Recurrent symptomatic VTE or related mortality: 2.3 vs 2.7a
| Recurrent symptomatic VTE or related mortality: 3.2 vs 3.5a
|
Primary Safety Outcome(s) | Major bleeding; Major or CRNM bleeding: Any bleeding | Major bleeding Major or CRNM bleeding: Any bleeding | Major or CRNM bleeding | Major or CRNM bleeding | Major bleeding | Major or CRNM bleeding |
Major Bleeding DOAC vs VKA (%) | 1.6 vs 1.9 | 1.2 vs 1.7 | 0.8 vs 1.2 | 1.1a vs 2.2 | 0.6a vs 1.8 | 1.4 vs 1.6 |
Major or CRNM Bleeding DOAC vs VKA (%) | 5.6 vs 8.8 | 5.0 vs 7.9 | 8.1 vs 8.1 | 10.3 vs 11.4 | 4.3a vs 9.7 | 8.5a vs 10.3 |
Management of VTE in patients with cancer
Trial Name | CANTHANOX | CLOT | MAIN-LITE | ONCENOX | CATCH |
---|---|---|---|---|---|
Year of Publication [Ref] | 2002 [43] | 2003 [44] | 2006 [45] | 2006 [46] | 2015 [47] |
Design | Open-label | Open-label | Open-label | Open-label | Open-label |
Number of Patients | 146 | 676 | 200 | 122 | 900 |
Treatment Protocol | Enoxaparin 1.5 mg/kg daily | Dalteparin 200 IU/kg once daily for the first month then 150 IU/kg for 5 months | Tinzaparin 175 IU/kg once daily | Enoxaparin 1 mg/kg every 12 h for 5 days then enoxaparin 1 mg/kg or 1.5 mg/kg daily | Tinzaparin 175 IU/kg once daily |
Duration of Therapy (months) | 3 | 6 | 3 | 6 | 6 |
Primary Efficacy Outcome LMWH vs VKA (%) | Combination of major bleeding or recurrent VTE: 10.5 vs 21.1 | Recurrent symptomatic VTE: 9a vs 17 | Recurrent symptomatic VTE: 7 vs 10 | Recurrent symptomatic VTE: enoxaparin 1 mg vs. 1.5 mg vs VKA 6.8 vs 6.3 vs 10.0 | Composite of recurrent symptomatic VTE, fatal PE, or incidental VTE: 7.2 vs 10.5 |
Safety Bleeding Outcomes LMWH vs VKA (%) | Major bleeding: 7 vs 16; Fatal bleeding: 0 vs 8a
| Major bleeding: 6 vs 4; Any bleeding 14 vs 19 | Major bleeding: 7 vs 7; Any bleeding: 27 vs 24 | Major bleeding: enoxaparin 1 mg vs. 1.5 mg vs VKA : 6.5 vs 11.1 vs 2.9 | Major bleeding: 2.7 vs 2.4 CRNM bleeding: 10.9a vs 15.3 |
Extended treatment of venous thromboembolism
Trial Name | EINSTEIN-EXTENSION | AMPLIFY-EXT | RE-MEDY | RE-SONATE |
---|---|---|---|---|
Year of Publication [Ref] | 2010 [17] | 2013 [50] | 2013 [51] | 2013 [51] |
Design | Double-blinded | Double-blinded | Double-blinded | Double-blinded |
Comparison Arm | Placebo | Placebo | Warfarin | Placebo |
Number of Patients | 1197 | 2486 | 2866 | 1353 |
Treatment Protocol | Rivaroxaban 20 mg once daily | Apixaban 5 mg or 2.5 twice daily | Dabigatran 150 mg twice daily | Dabigatran 150 mg twice daily |
Duration of Therapy (months) | 6 to12 | 12 | 6 to 36 | 6 |
Primary Efficacy Outcome DOAC vs VKA or Placebo (%) | Recurrent symptomatic VTE: 1.3a vs 7.1 | Recurrent symptomatic VTE or all-cause mortality: 3.8a vs 4.2a vs 11.6 | Recurrent symptomatic VTE or related mortality: 1.8a vs 1.3 | Recurrent symptomatic VTE or related mortality: 0.4a vs 5.6 |
Major Bleeding DOAC vs VKA or Placebo (%) | 0.7 vs 0 | 0.2 vs 0.1 vs 0.5 | 0.9 vs 1.8 | 0.3 vs 0 |
Major and CRNM Bleeding DOAC vs VKA or Placebo (%) | 6.0a vs 1.2 | 3.2 vs 4.3 vs 2.7 | 5.6a vs 10.2 | 5.3a vs 1.8 |
Treatment of VTE in special situations
Management of sub-segmental pulmonary embolism
Study | Musset et al. | Eyer et al. | Donato et al. | Pena et al. | Mehta et al. | Goy et al. | Ghazvinian et al. |
---|---|---|---|---|---|---|---|
Year of Publication [Ref] | 2002 [59] | 2005 [60] | 2010 [61] | 2012 [62] | 2014 [63] | 2015 [64] | 2016 [65] |
Method of Detection | SDCT | MDCT | MDCT | MDCT | MDCT | MDCT | V/P SPECT |
Number of Patient with Positive CTPA | 360 | 499 | 1463 | 724 | NAb
| 550 | NAb
|
Number of Patients with SSPE n/N (%) | 12 (3.3) | 67 (13.4) | 93 (6.4) | 70 (9.6) | 32 (100) | 82 (15) | 54 (100) |
Number of Untreated SSPE (%) | 9 (75) | 25 (37.3) | 22 (22.9) | 18 (25.7) | 12 (37.5) | 39 (47.6) | 54 (100) |
VTE (%) | 0 | 0 | 0 | 0 | 0 | 0 | 4a
|