Phase III trials of new oral anticoagulants in the acute treatment and secondary prevention of VTE: comparison and critique of study methodology and results

Abstract

The traditional treatment of venous thromboembolism (VTE) has been use of heparin and vitamin K antagonists (VKA), and although shown to be effective, they have numerous limitations. New oral anticoagulants (NOACs) including direct thrombin (factor IIa) inhibitors (dabigatran) and selective factor Xa inhibitors (rivaroxaban, apixaban and edoxaban) have emerged as promising alternatives with the potential to overcome the limitations of traditional treatments. Clinical trials have been performed with a view to making significant changes to the acute, long-term and extended treatment of VTE. Data are now available on the efficacy and safety, including bleeding rates, of the NOACs in comparison with VKA in the acute treatment and secondary prevention of VTE as well as in comparison with placebo extended VTE treatment. This review compares and contrasts the design and results of the Phase III trials of NOACs in VTE and discusses the implications of the NOACs in terms of treatment strategies in VTE patients.

Fig. 1

VTE recurrence and rates of major or CRNM bleeding in VTE studies that compared NOACs with either LMWH and VKAs or VKAs. CI confidence interval, CRNM clinically relevant non-major. DVT deep-vein thrombosis, HR hazard ratio, LMWH low molecular weight heparin, NOAC new oral anticoagulant, VKA vitamin K antagonist, VTE venous thromboembolism [–27]

Fig. 2

VTE recurrence and rates of major or CRNM bleeding in placebo-controlled VTE extension studies of NOACs. CI confidence interval, CRNM clinically relevant non-major, HR hazard ratio, NOAC new oral anticoagulant, VTE venous thromboembolism [20, 21, 24]