Adherence to direct oral anticoagulants in patients with non-valvular atrial fibrillation cross-national comparison in six european countries

Introduction: Since 2011 direct oral anticoagulant drugs (DOACs) have been approved for the prevention of stroke in patients with non-valvular atrial fibrillation (NVAF).Different studies showed that treatment adherencewithDOACs is higher than with VKA, but the comparisons are scarce and results are contradictory. Objectives: To describe the adherence to three DOAC compounds using information from eight European databases (Mondriaan, Danish National Registers, Bavarian, AOK Nordwest, BIFAP, SIDIAP, CPRD and EGB) representing six European countries (The Netherlands, Denmark, Germany, Spain, United Kingdom and France). Methods: Retrospective cohort study of new users (aged ≥18 years) of DOACs (dabigatran, rivaroxaban, apixaban) with a diagnosis of NVAF identified from eight electronic health care databases (2008-2015). Switching and discontinuation percentages and probability of continuation, using the the Kaplan-Meier method, were estimated for all DOACs and for each individual DOAC at 3, 6 and 12 months. Results: For all DOAC Mondriaan was the database with the lowest proportions of switchers (2.4%), EGB showed the highest proportions of switchers (13.1%) at 12 months. Regarding discontinuers CPRD had the lowest percentage (16%) and the Bavarian database the highest (63.9%). Discontinuers where most often patients using dabigatran (23.2% CPRD-64.6% Mondriaan), except in the Bavarian database where apixaban had the highest proportion (69.5%) and in the AOK Nordwest where rivaroxaban had the highest proportion (40.2%), followed by rivaroxaban (15.5% CPRD-50.2% Mondrian) and apixaban (12.3% CPRD-46.3% Mondriaan). Apixaban showed the highest probability of continuation at 12 months (range: 0.6-0.8), except inMondriaan (rivaroxaban 0.43) and in AOK Nordwest (dabigatran 0.64). Dabigatran had the lowest probability of continuation at 12 months (range: 0.2-0.7), except in AOK Nordwest (apixaban 0.46). Summary / Conclusions: Dabigatran was the DOAC with the highest proportion of discontinuers and switchers and apixaban had the lowest one, in most databases. More research is needed to evaluate whether low discontinuation rates for apixaban translate into lower rates of cerebrovascular outcomes and bleeding episodes. This study was funded by the European Medicines Agency (EMA/2015/27/PH; EU PAS Register No: 16014).