Comparative Effects Between Direct Oral Anticoagulants for Acute Venous Thromboembolism: Indirect Comparison From Randomized Controlled Trials

Background: There is no direct comparison from clinical trials amongst the direct oral anticoagulants (DOACs) in patients with acute venous thromboembolism (VTE), leaving an evidence gap in decision-making regarding the choice of a DOAC. Methods: We performed a systematic review for an indirect comparison from randomized controlled trials (RCTs) for comparative effects amongst DOACs in the patients with acute VTE. Results: A total of 16 RCTs were included for analyses, among which three for dabigatran (n = 7,963 patients), six rivaroxaban (n = 17,935), five apixaban (n = 12,823), and two edoxaban (n = 9,286). There was no significant difference in risk of recurrent VTE (evidence quality: low) and major bleeding (evidence quality: very low) for treatment effects between the four DOACs. Albeit non-significantly, apixaban seemed to have a lowest risk of major bleeding while rivaroxaban had a smallest risk of VTE. Although in general all the included trials were comparable, data from the included trials indicated that the assumption of transitivity may be challenged. Further methodological research including simulation studies, using a net-benefit or benefit-harm approach, running ranking probability analysis, and developing decision aids with machine-learning may be a worthwhile endeavor to help with the choice of DOACs in patients with acute VTE. Conclusions: To conclude, based on results from the indirect comparison no significant difference in the efficacy and safety was found among the DOACs in patients with acute VTE. More evidence from direct comparative trials is needed to further inform the choice of DOACs in patients with acute VTE.