Venous thromboembolism therapy with rivaroxaban in daily-care patients: Results from the Dresden NOAC registry
Introduction
Although vitamin K antagonists (VKA) have been the standard anticoagulation therapy for patients with venous thromboembolism (VTE) for decades, they are more and more replaced by direct-acting, non-vitamin K antagonist oral anticoagulants (NOAC), which demonstrate a much better dose–response relationship and less interactions with food or co-medications and, therefore, do not require routine monitoring and frequent dose adjustments [1], [2]. The NOAC rivaroxaban is a direct factor Xa inhibitor that is approved for the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), based on the results of two large phase III trials (EINSTEIN DVT and EINSTEIN PE), in which rivaroxaban demonstrated non-inferior efficacy to VKA [3], [4], [5]. Even more important, in a pooled analysis of the EINSTEIN DVT and PE trials rivaroxaban demonstrated superior safety over VKA with an absolute risk reduction for major bleeding of 0.8%, which translated into a relative risk reduction of 46% [5].
However, the external validity of phase III trials needs to be confirmed in daily-care settings, in which patients may have significant co-morbidities and are treated without a strict protocol under less intense surveillance, also because the specific design of phase-III trial protocols can have a major impact on outcomes [6]. Consequently, observational studies are needed to confirm trial findings of rivaroxaban in daily-care settings. Furthermore, such studies should not only evaluate short-term outcomes of VTE treatment but should include a long-term follow up and also evaluate patients who continue oral anticoagulation beyond the initial therapy as well as patients who discontinue anticoagulation therapy for whatever reason.
Using data from an ongoing large multicentric cross-indicational NOAC registry, we prospectively evaluated the management and long-term outcome of patients with VTE treated with rivaroxaban.
Section snippets
Patients
The Dresden NOAC Registry (NCT01588119) is a prospective registry in the administrative district of Dresden (Saxony), Germany. In this ongoing project, a network of > 230 physicians from private practices and hospitals are enrolling consecutive NOAC recipients treated for VTE or atrial fibrillation. All patients are prospectively followed up by the central registry office. The design and methodology of the Dresden NOAC Registry has been published previously [7], [8], [9], [10], [11], [12].
Results
Between December 1st 2011 and 30th September 2016, a total of 878 patients receiving rivaroxaban for VTE treatment were enrolled. Of these, 418 patients were treated for acute lower limb DVT and/or PE, started rivaroxaban and were enrolled into the registry within 14 days after VTE diagnosis (Fig. 1). These patients constituted the study cohort for the present analysis and, of these, 337 (80.6%) were enrolled with isolated DVT without confirmed PE and 81 (19.4%) patients had an objectively
Discussion
In a large cohort of patients treated with rivaroxaban for acute VTE in daily care, we confirmed the effectiveness and safety of rivaroxaban seen in phase III studies. In the EINSTEIN phase III trials which did not report annualized rates, absolute rates of recurrent VTE and ISTH major bleeding were 2.1% and 1.0% respectively for patients treated for 3–12 months [3], [4]. In our study, recurrent VTE occurred in 1.9% of patients (1.8/100 pt. years) and ISTH major bleeding in 3.8% of patients
Limitations
There are several limitations to our study, which have been discussed in detail in our previous publications [9], [11], [16], [26].
Conclusion
In daily care, rivaroxaban treatment for acute VTE is effective and acceptably safe. We found initial rivaroxaban dosing to be in accordance with label in over 90% of patients and, at 6 and 12 months, persistence to rivaroxaban therapy was high with low rates of unplanned complete discontinuation. Fatal VTE and fatal bleeding are rare events during rivaroxaban therapy and all-cause mortality is mostly related to underlying diseases, age or acute conditions. Treatment discontinuation resulted in
Funding
The NOAC registry is supported by the Gesellschaft für Technologie- und Wissenstransfer der Technischen Universität Dresden (GWT-TUD GmbH), Germany (sponsor); by research funds of the University Hospital “Carl Gustav Carus”, Dresden, and by grants from Bayer HealthCare, Boehringer Ingelheim, Daiichi Sankyo and Pfizer. All authors declare that these companies and institutions had no influence on the study design, conduct of the study, data collection, statistical analysis, or preparation of the
Acknowledgements
We are grateful to all participating patients and physicians, who continue to be maximally supportive in helping to follow patients and provide detailed information/documentation on suspected outcome events.
Conflict of interest
J.B.-W. has received honoraria and research support from Bayer HealthCare, Boehringer Ingelheim, Daiichi Sankyo, Pfizer and Portola. S.M. has received honoraria from Bayer HealthCare and Daiichi Sankyo. None of the other authors declared a conflict of interest with regard to the NOAC registry or this manuscript.
Authors' contributions
J.B.-W. has designed this analysis. L.T. has written the first draft of the manuscript. L.K., S.M. and J.H. have collected the data. K.S. and L.T. has performed the statistical analyses and drafted the figures. All authors have provided significant contributions to the written presentation, have critically reviewed and approved the final version of the manuscript.
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