Real-World Edoxaban Safety Monitoring in European Afib Patients

The Edoxaban Treatment in Routine Clinical Practice for Patients With Non Valvular Atrial Fibrillation (ETNA-AF-Europe) was designed as part of the risk management plan of edoxaban in order to assess the risks and benefits of the drug in routine care in unselected European patients with AF. ETNA-AF-Europe is part of the global ETNA initiative, which is composed of separate, non-interventional prospective ETNA-AF registries in Europe, East Asia, Brazil and Japan. The final ETNA-AF-Europe protocol was developed based on discussions with, and finally approved by the Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency. The primary objective of ETNA-AF Europe is to assess the safety of edoxaban by evaluating bleeding events, including intracranial haemorrhage; drug related adverse events, such as liver adverse events; and cardiovascular (CV) as well as all-cause mortality in routine care patients with AF treated with edoxaban up to 4 years, with regard to onset (relative to treatment with edoxaban) of the event, duration, severity and outcomes.
Details of the design of ETNA-AF-Europe including the statistical rationale have been published [21 (link)]. In short, ETNA-AF-Europe is a multinational, multi-centre, post-authorisation, observational study (Clinicaltrials.gov: NCT02944019) conducted in 825 sites (with at least one patient enrolled) in 10 European countries. All patients with non-valvular AF treated with edoxaban according to the summary of product characteristics (SmPC), could participate in the study with prior provision of written informed consent and no simultaneous participation in an interventional trial. No explicit exclusion criteria were defined. Over a period of 3 years, ETNA-AF-Europe enrolled 13,980 patients with AF confirmed within the last 12 months before enrolment. AF had to be confirmed by the investigators by electrical tracing (e.g., ECG, Holter monitoring, pacemaker or other implantable device). Detailed information on AF history and diagnosis, and on previous AF-related therapies was collected, including former anticoagulant treatment with VKAs, NOACs or heparins; previous or current antiplatelet drugs, antiarrhythmic and rate-control drugs and other therapies. The CHA₂DS₂-VASc and HAS-BLED scores were both reported by the investigators as well as calculated based on the baseline clinical characteristics of the patients. For the analysis here reported, calculated scores are used. Specific subgroup analyses are planned by edoxaban dose, patient age and country. Figure 1 provides an overview of the patient disposition in ETNA-AF-Europe. Of 13,980 enrolled patients, 13,638 were included in the baseline analysis set. Patients are to be followed up once a year for a total of 4 years.Fig. 1

Overview of the ETNA-AF-Europe registry. *Some patients fulfilled more than one exclusion criteria

The patient baseline characteristics from ENGAGE AF-TIMI 48 are used as an external comparator to the baseline data collected in ETNA-AF-Europe to better understand how the usage of edoxaban in routine clinical practice reflects on the trial setting in which edoxaban was tested. The ENGAGE AF-TIMI 48 cohort used for this purpose includes patients from only those European countries that are also participating in the ETNA-AF-Europe registry.