Research in context
Evidence before this study
We did not do a formal literature search before we started the XALIA study because at study initiation, EINSTEIN DVT was the only study of a direct oral anticoagulant without parenteral pre-treatment to be published and so there were no published contemporary references. The phase 3 EINSTEIN DVT trial showed similar rates of recurrent venous thromboembolism and major bleeding with rivaroxaban treatment compared with standard anticoagulation (low-molecular-weight heparin, overlapping with and followed by a dose-adjusted vitamin K antagonist) for the treatment of acute deep-vein thrombosis. Additionally, in EINSTEIN EXT, extended treatment with rivaroxaban was superior to placebo for the prevention of venous thromboembolism, with an acceptable risk of bleeding. Subsequent to these studies, rivaroxaban (15 mg twice daily for 21 days, followed by 20 mg once daily) became the first direct oral anticoagulant to be approved by the European Medicines Agency for the treatment of acute deep-vein thrombosis and secondary prevention of venous thromboembolism in December, 2011. In June, 2012, the EINSTEIN PE trial showed that rivaroxaban was non-inferior to standard of care, with a significant reduction in major bleeding events; this finding formed the basis of the regulatory approval for the treatment of acute pulmonary embolism in December, 2012. The XALIA study was initiated on June 26, 2012, and on Aug 15, 2013, following the approval by the European Medicines Agency of rivaroxaban for the treatment of pulmonary embolism, the study protocol was amended to allow patients with deep-vein thrombosis and concomitant pulmonary embolism into the study, although patients with isolated pulmonary embolism were still ineligible.
Added value of this study
XALIA is the first prospective, non-interventional study of the safety and effectiveness of a direct oral anticoagulant for the treatment of deep-vein thrombosis, which also included patients with concomitant pulmonary embolism. Propensity score-adjusted analyses showed the rates of major bleeding and recurrent venous thromboembolism to be similar to those recorded with standard anticoagulation therapy (a parenteral agent overlapping with, and followed by, a vitamin K antagonist). Additionally, rivaroxaban was associated with shorter hospital stays than occurred in patients receiving standard anticoagulation therapy.
Implications of all the available evidence
This study is the first international, prospective, non-interventional study of a direct oral anticoagulant, and it shows that the findings from the phase 3 studies of rivaroxaban can be translated to patients with deep-vein thrombosis treated in routine practice. With fixed-dosing regimens and no routine coagulation monitoring, rivaroxaban as a single-drug therapy has the potential to simplify the management of patients with venous thromboembolism, which could offer advantages over the conventional dual-drug anticoagulant therapy.