From: Treatment options for venous thromboembolism: lessons learnt from clinical trials
Drug | Indication | Study name | Treatments | Main findings |
---|---|---|---|---|
Rivaroxaban | Acute treatment of DVT without PE | EINSTEIN DVT [32] | Rivaroxaban 15 mg bid for 3 weeks, then 20 mg od for 3–12 months or Enoxaparin for ≥5 days with VKA (target INR 2.0–3.0) for 3–12 months | VTE recurrence for rivaroxaban vs LMWH/VKA 2.1% vs 3.0% (HR 0.68; 95% CI 0.44–1.04; p < 0.001 for non-inferiority; p = 0.08 for superiority). Major or non-major clinically relevant bleeding for rivaroxaban vs LMWH/VKA 8.1% vs 8.1% (HR 0.97; 95% CI 0.76–1.22; p = NS) |
 | Acute treatment of PE with or without DVT | EINSTEIN PE [33] | Rivaroxaban 15 mg bid for 3 weeks, then 20 mg od for 3–12 months or Enoxaparin for ≥5 days with VKA (target INR 2.0–3.0) for 3–12 months | VTE recurrence for rivaroxaban vs LMWH/VKA 2.1% vs 1.8% (HR 1.12; 95% CI 0.75–1.68; p = 0.003 for non-inferiority). Major or non-major clinically relevant bleeding for rivaroxaban vs LMWH/VKA 10.3% vs 11.4%; p = NS |
 | Secondary prevention of VTE | EINSTEIN EXT [32] | After completion of 6–12 months’ treatment: Rivaroxaban 20 mg od for 6 or 12 months or Placebo for 6 or 12 months | VTE recurrence for rivaroxaban vs placebo 1.3% vs 7.1% (HR 0.18; 95% CI 0.09–0.39; p < 0.001 for superiority). Major bleeding for rivaroxaban vs placebo 0.7% vs 0% (HR not available; p = 0.11) |
Apixaban | Acute treatment of VTE | AMPLIFY | Apixaban 10 mg bid for 7 days then 5 mg bid for 6 months or Enoxaparin 1 mg/kg (s.c.) bid until INR ≥2, warfarin (target INR 2.0–3.0) | VTE recurrence or VTE-related death for apixaban vs LMWH/warfarin 2.3% vs 2.7% (RR 0.84; 95% CI 0.60–1.18; p < 0.001 for non-inferiority for apixaban). Major bleeding for apixaban vs LMWH/warfarin 0.6% vs 1.8% (RR 0.31; 95% CI 0.17–0.55; p < 0.001 for superiority for apixaban) |
 | Secondary prevention of VTE | AMPLIFY-EXT [37] | After 6–12 months of apixaban or warfarin: Apixaban 2.5 mg or 5 mg bid for 12 months or Placebo for 12 months | VTE recurrence or any-cause death for apixaban 2.5 mg or 5.0 mg vs placebo, 3.8% or 4.2% vs 11.6% (2.5 mg RR 0.33; 95% CI 0.22–0.48; 5 mg RR 0.36; 95% CI 0.25–0.53; p < 0.001 for superiority for both apixaban doses). Major bleeding for apixaban 2.5 mg or 5.0 mg vs placebo, 0.2% (RR 0.49; 95% CI 0.09–2.64) or 0.1% (RR 0.25; 95% CI 0.03–2.24) vs 0.5% (p values not available) |
Edoxaban | Acute treatment of VTE | Hokusai-VTE [39] | LMWH or UFH for ≥5 days then edoxaban 60 mg od for 3–12 months or LMWH or UFH for ≥5 days then warfarin (target INR 2.0–3.0) for 3–12 months | VTE recurrence or VTE-related death for edoxaban vs warfarin 3.2% vs 3.5% (HR 0.89; 95% CI 0.70–1.13; p < 0.001 for non-inferiority for edoxaban). First major or non-major clinically relevant bleeding event 8.5% vs 10.3% (HR 0.81; 95% CI 0.71–0.94; p = 0.004 for superiority for edoxaban) |
 | Acute treatment of VTE | eTRIS (NCT01662908) | Edoxaban 90 mg od for 10 days then 60 mg od (total 90 days) or Warfarin (target INR 2.0–3.0) for 90 days, with enoxaparin or UFH for ≥5 days until target INR reached | Ongoing |
Dabigatran | Acute treatment of VTE | RE-COVER [35] | LMWH or UFH for ≥5 days; dabigatran 150 mg bid for 6 months or LMWH or UFH for ≥5 days; warfarin (target INR 2.0–3.0) for 6 months | VTE recurrence for dabigatran vs warfarin 2.4% vs 2.1% (HR 1.10; 95% CI 0.65–1.84; p < 0.001 for non-inferiority). Major bleeding for dabigatran vs warfarin 1.6% vs 1.9% (HR 0.82; 95% CI 0.45–1.48; p = 0.38) |
 | Acute treatment of VTE | RE-COVER II [36] | LMWH or UFH for 5–11 days; dabigatran 150 mg bid for 6 months or LMWH or UFH for 5–11 days; warfarin (target INR 2.0–3.0) for 6 months | VTE recurrence or VTE-related death for dabigatran vs warfarin 2.3% vs 2.2% (HR 1.08; 95% CI 0.64–1.80; p < 0.001 for non-inferiority)*. Major bleeding for dabigatran vs warfarin 1.2% vs 1.7% (HR 0.69; 95% CI 0.36–1.32; p value not available) |
 | Secondary prevention of VTE | RE-MEDY [38] | After 3–12 months of anticoagulant therapy: Dabigatran 150 mg bid for 6–36 months or Warfarin (target INR 2.0–3.0) for 6–36 months | VTE recurrence for dabigatran vs warfarin 1.8% vs 1.3% (HR 1.44; 95% CI 0.78–2.64; p = 0.01 for non-inferiority). Major bleeding for dabigatran vs warfarin 0.9% vs 1.8% (HR 0.52; 95% CI 0.27–1.02; p = 0.06) |
 | Secondary prevention of VTE | RE-SONATE [38] | After 6–18 months of anticoagulant therapy: Dabigatran 150 mg bid for 6 months or Placebo for 6 months | VTE recurrence for dabigatran vs placebo 0.4% vs 5.6% (HR 0.08; 95% CI 0.02–0.25; p < 0.001). Major bleeding for dabigatran vs placebo 0.39% vs 0% (HR not available; 95% CI 0.04–1.05; p = 0.5) |