title: Indirect comparison of dabigatran, rivaroxaban, apixaban and edoxaban for the treatment of acute venous thromboembolism.
abstract: 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.
authors.affiliation: Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY, 10065, USA, manthas@mskcc.org.
authors.forename: Simon
authors.initials: S
authors.lastname: Mantha
authors.forename: Jack
authors.initials: J
authors.lastname: Ansell
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects; D017326:Clinical Trials, Phase III as Topic; D000069604:Dabigatran / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced* / Q000517:prevention & control; D006801:Humans; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D011655:Pulmonary Embolism / Q000175:diagnosis / Q000188:drug therapy / Q000401:mortality; D011720:Pyrazoles / Q000008:administration & dosage / Q000009:adverse effects; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects; D011728:Pyridones / Q000008:administration & dosage / Q000009:adverse effects; D012008:Recurrence; D018570:Risk Assessment; D000069552:Rivaroxaban / Q000008:administration & dosage / Q000009:adverse effects; D016019:Survival Analysis; D013844:Thiazoles / Q000008:administration & dosage / Q000009:adverse effects; D020246:Venous Thrombosis / Q000175:diagnosis / Q000188:drug therapy / Q000401:mortality
chemical_list: D000925:Anticoagulants; D011720:Pyrazoles; D011725:Pyridines; D011728:Pyridones; D013844:Thiazoles; C522181:apixaban; D000069552:Rivaroxaban; D000069604:Dabigatran; C552171:edoxaban