Incidence of direct oral anticoagulation use for non valvular atrial fibrillation and characteristics of users in six European countries (2008-2015) : A cross-national drug utilization study

Background: The newer direct oral anticoagulants (DOACs) have been approved by the European Union since 2008. Utilization of DOACs for stroke prevention in non-valvular atrial fibrillation (NVAF) and their effectiveness and safety in clinical practice have been assessed in several European countries. However, little is still known about their use beyond the clinical trial conditions, especially in patients with hepatic or renal impairment. Objectives: To estimate the incidence of Direct Oral Anticoagulant Drugs use in non-valvular atrial fibrillation (NVAF) and to describe user and treatment characteristics in 8 European health databases (Mondriaan, Bavarian CD, AOK Nordwest, BIFAP, SIDIAP, CPRD, EGB and DNR) representing 6 European countries (The Netherlands, Germany, Spain, United Kingdom, France and Denmark). Methods: Descriptive cohort study from January 2008 to December 2015. A common protocol approach was applied. Annual period incidences and direct standardization by age and sex were performed. An incidence percentage change in DOAC use, dose adjustment related to change in age and by renal function as well as concomitant use of potential interacting drugs during first DOAC episode were assessed. Results: A total of 186,405 new DOAC users (≥18 years) were identified. The standardized incidence increased for all DOACs over the study period, with the highest increase for apixaban (554.5%) followed by rivaroxaban (80.7%). The highest incidence for all DOACs was found in Denmark and Germany, with lower values and slight differences among the remaining databases. The incidence of DOAC use increased for both genders in most databases and especially in those older than 75. Concomitant use of contraindicated drugs varied between 16.4% (SIDIAP), and 70.5% (EGB) and dose adjustment ranged from 4.6% in the Spanish (BIFAP) to 15.6% in the French (EGB) population. Conclusions: The overall incidence of new DOAC users increased, with the highest increase for apixaban. Cross national drug utilization studies with a standard protocol may help to compare drug use and enable health care decisions.