Comparison of clinical outcomes with edoxaban versus apixaban, dabigatran, rivaroxaban, and vitamin K antagonist in patients with atrial fibrillation in Germany: a real-world cohort study
Authors: Marston X.L , Wang R , Yeh Y.C , Zimmermann L , Ye X , Gao X , Unverdorben M 
Published: November 2020

Abstract

Background
Vitamin K antagonists (VKA) and non-VKA oral anticoagulants (NOACs) are used to prevent thromboembolic conditions in patients with atrial fibrillation (AF). Unlike VKA, NOACs have fixed dosage schemes, do not require regular laboratory tests, and have fewer drug and food interactions. The use of NOACs has increased substantially in recent years in Germany. However, there is limited evidence on the comparative effectiveness and safety between different NOACs and VKA in real-world settings.

Purpose
The objective of the study was to compare the clinical outcomes, including systemic embolism (SE), ischemic stroke (IS), and major bleeding, of edoxaban with other NOACs (apixaban, dabigatran, rivaroxaban) and VKA in AF patients in Germany.

Methods
Using an administrative database from our institution (Deutsche Analysedatenbank für Evaluation und Versorgungsforschung) between January 2013 and December 2017, a retrospective cohort study was conducted to compare the effectiveness (risk of SE or IS) and safety (risk of major bleeding) in NOAC-naïve AF patients who initiated anticoagulant therapy. Continuous enrolment for 12 months before anticoagulant initiation was required to assess baseline characteristics. Patients were followed up until (1) the first outcome event (SE, IS, or major bleeding), (2) disenrollment from health plans, or (3) discontinuation of the index NOAC or VKA or therapy switch, whichever occurred first. Inverse probability treatment weighting (IPTW) using propensity score was applied to control for differences in baseline characteristics. Cox proportional hazards models were used to estimate the hazard ratios (HR) for each outcome comparing edoxaban versus other NOACs and VKA. Sensitivity analyses were conducted with follow-up period cut-off at 1 year.

Results
A total of 1236 edoxaban, 6053 apixaban, 1306 dabigatran, 7013 rivaroxaban, and 5430 VKA patients were included. Patient cohorts were well balanced after weighting. The adjusted risks of SE or IS were lower for edoxaban compared to apixaban (HR 0.83, 95% CI 0.69–0.99), dabigatran (HR 0.54, 95% CI 0.40–0.74), rivaroxaban (HR 0.72, 95% CI 0.60–0.87), and VKA (HR 0.65, 95% CI 0.53–0.78) (all p&lt;0.05). Edoxaban was associated with a significantly lower risk of major bleeding compared to dabigatran (HR 0.73, 95% CI 0.55–0.98), rivaroxaban (HR 0.74, 95% CI 0.63–0.87), and VKA (HR 0.47, 95% CI 0.40–0.55) (all p&lt;0.05). The risk of major bleeding was comparable between edoxaban and apixaban (HR 1.09, 95% CI 0.92–1.30, p=0.33). Results were consistent in the sensitivity analyses.

Conclusions
Edoxaban was associated with a significantly lower risk of SE or IS compared to other NOACs and VKA, indicating improved effectiveness. Edoxaban also had a favourable safety profile with a significantly lower risk of major bleeding compared to dabigatran, rivaroxaban, and VKA.

Funding Acknowledgement
Type of funding source: Private company. Main funding source(s): This study was sponsored by Daiichi Sankyo Inc.