Indirect comparison of dabigatran, rivaroxaban, apixaban and edoxaban for the treatment of acute venous thromboembolism

Four target-specific oral anticoagulants (TSOA’s) have been compared to a vitamin K antagonist for the treatment of acute venous thromboembolism (VTE): dabigatran (D), rivaroxaban (R), apixaban (A) and edoxaban (E). We performed an indirect comparison of the TSOA’s, based on the six phase III trials identified (RE-COVER I, RE-COVER II, EINSTEIN-DVT, EINSTEIN-PE, AMPLIFY and Hokusai-VTE). There was no statistically significant difference in risk of recurrent VTE or all-cause mortality between the TSOA’s. For major bleeding, the RR of an event was 0.42 (95 % CI 0.21–0.87, p = 0.02) for A versus D, compared with 0.57 (95 % CI 0.29–1.15, p = 0.12) for A versus R, 0.37 (95 % CI 0.19–0.73, p < 0.001) for A versus E, 0.74 (95 % CI 0.42–1.30, p = 0.30) for R versus D, 0.64 (95 % CI 0.38–1.08, p = 0.10) for R versus E and 1.15 (95 % CI 0.66–2.00, p = 0.62) for E versus D. For the composite endpoint of major or clinically relevant nonmajor bleeding, the RR was 0.71 (95 % CI 0.53–0.96, p = 0.02) for A versus D, 0.47 (95 % CI 0.37–0.61, p < 0.001) for A versus R, 0.54 (95 % CI 0.42–0.70, p < 0.001) for A versus E, 1.50 (95 % CI 1.17–1.92, p = 0.001) for R versus D, 1.15 (95 % CI 0.95–1.39, p = 0.16) for R versus E and 1.31 (95 % CI 1.02–1.68, p = 0.04) for E versus D. Overall, apixaban appears to be associated with a lower risk of bleeding than the other TSOA’s. This analysis may be helpful to the clinician in trying to balance risk versus benefit in selecting a new anticoagulant. A dedicated randomized trial directly comparing the new agents would be required to confirm these results.