Table 1.
Major randomized trials in extended anticoagulation after the first episode of VTE.
| Trial | Year | n | Drugs evaluated | Major findings |
|---|---|---|---|---|
| Kearon et al.13 | 1999 | 162 (Unprovoked) |
Warfarin versus placebo for 24 months | Reduction in VTE recurrence of 95% (p < 0.001). VTE recurrence warfarin 1.3% versus 27.4% placebo. Major bleeding 3.8% versus 0 placebo (p = 0.09) |
| PREVENT14 | 2003 | 508 (Unprovoked) | Low-intensity warfarin (INR 1.5–1.9) versus
placebo. Mean of follow up 2.1 years |
Reduction in VTE recurrence of 64% (p < 0.05). VTE recurrence, low-intensity warfarin 2.6% versus 7.2% placebo. Major bleeding 5 patients versus 2 placebo (p = 0.25) |
| ELATE15 | 2003 | 738 (Unprovoked) | Low-intensity warfarin (INR 1.5–1.9) versus
Conventional warfarin Mean of follow up 2.4 years |
Conventional warfarin with fewer VTE events (0.7% versus 1.9% p < 0.05) and the same major bleeding rates (0.9% versus 1.1%) |
| EINSTEIN-EXT39 | 2010 | 1196 (70% unprovoked) | Rivaroxaban versus placebo followed for 6 or 12 months | Reduction in VTE recurrence of 82% (p < 0.001). VTE recurrence, rivaroxaban 1.3% versus 7.1% placebo. Major bleeding, 0.7% versus 0 placebo |
| WARFASA30 | 2012 | 402 (Unprovoked) | Aspirin versus placebo followed for 2 years | VTE recurrence 6.6% aspirin versus 11.2% placebo per year. HR 0.58; 95% CI 0.36–0.93. No difference in major bleeding |
| ASPIRE31 | 2012 | 822 (Unprovoked) | Aspirin versus placebo followed for 4 years | VTE recurrence 4.8% aspirin versus 6.5% placebo per year. HR 0.74; 95% CI 0.52–1.05. No difference in major bleeding |
| RE-SONATE40 | 2013 | 1353 | Dabigatran versus placebo followed for 6 or 12 months | Reduction in VTE recurrence of 92% with dabigatran (0.4 versus 5.6%; HR 0.08; 95% CI 0.02–0.25). Major bleeding 0.3% versus 0 placebo |
| RE-MEDY41 | 2013 | 2856 | Dabigatran versus warfarin followed for 6 months | Dabigatran was noninferior to warfarin in VTE recurrence (1.8 versus 1.3%; HR 1.44; 95% CI 0.27–1.02; p = 0.01 for noninferiority), and induced less clinically relevant bleeding (5.6 versus 10.2%; HR 0.54; 95% CI 0.41–0.71) |
| AMPLIFY-EXT43 | 2013 | 2486 (90% unprovoked) | Apixaban 2.5 mg 2 × d (prophylactic dosage) versus Apixaban 5 mg 2 × d (anticoagulation dosage) versus placebo followed for 12 months | Recurrent VTE occurred in 8.8% placebo, 1.7% apixaban prophylactic, 1.7% in the apixaban anticoagulation (p < 0.001). Major bleeding 0.5% placebo, 0.2% apixaban prophylactic, 0.1% apixaban anticoagulation |
| SURVET34 | 2015 | 615 (Unprovoked) | Sulodexide 50 mg 2 × d versus placebo followed for 2 years | VTE recurrence 4.9% sulodexide, 9.7% placebo (p = 0.025). No major bleeding in both groups |
| EINSTEIN CHOICE33 | 2017 | 3396 (40% Unprovoked) | Aspirin 100 mg versus rivaroxaban 10 mg 1 × d (prophylactic dosage) versus rivaroxaban 20 mg 1 × d (anticoagulation dosage) followed for 12 months | VTE recurrence 4.4% aspirin, 1.2% rivaroxaban prophylactic 1.5% rivaroxaban anticoagulation (p < 0.001). Major bleeding 0.3% aspirin, 0.4% rivaroxaban prophylactic, 0.5% rivaroxaban anticoagulation |
VTE, venous thromboembolism.