Adherence to Direct Oral Anticoagulants in Patients With Non-Valvular Atrial Fibrillation: A Cross-National Comparison in Six European Countries (2008–2015)

Abstract

Aims: To describe and compare the adherence to different direct oral anticoagulants (DOACs) in eight European databases representing six countries.Methods: Longitudinal drug utilization study of new users (≥18 years) of DOACs (dabigatran, rivaroxaban, apixaban) with a diagnosis of non-valvular atrial fibrillation (2008–2015). Adherence was examined by estimating persistence, switching, and discontinuation rates at 12 months. Primary non-adherence was estimated in BIFAP and SIDIAP databases.Results: The highest persistence rate was seen for apixaban in the CPRD database (81%) and the lowest for dabigatran in the Mondriaan database (22%). The switching rate for all DOACs ranged from 2.4 to 13.1% (Mondriaan and EGB databases, respectively). Dabigatran had the highest switching rate from 5.0 to 20.0% (Mondriaan and EGB databases, respectively). The discontinuation rate for all DOACs ranged from 16.0 to 63.9% (CPRD and Bavarian CD databases, respectively). Dabigatran had the highest rate of discontinuers, except in the Bavarian CD and AOK NORDWEST databases, ranging from 23.2 to 64.6% (CPRD and Mondriaan databases, respectively). Combined primary non-adherence for examined DOACs was 11.1% in BIFAP and 14.0% in SIDIAP. There were differences in population coverage and in the type of drug data source among the databases.Conclusion: Despite the differences in the characteristics of the databases and in demographic and baseline characteristics of the included population that could explain some of the observed discrepancies, we can observe a similar pattern throughout the databases. Apixaban was the DOAC with the highest persistence. Dabigatran had the highest proportion of discontinuers and switchers at 12 months in most databases (EMA/2015/27/PH).

Adherence and persistence to oral anticoagulants in patients with atrial fibrillation: A Belgian nationwide cohort study

“…Differences in persistence to individual NOACs were in line with previous studies, which have demonstrated higher persistence to apixaban than to rivaroxaban or dabigatran ( 8 , 11 , 13 – 15 , 17 , 24 , 34 , 39 , 40 ), except for one study ( 41 ) in which persistence to rivaroxaban was highest. Likewise, other studies also observed predominant switching of dabigatran followed by rivaroxaban ( 30 , 39 – 41 ).…”

“…Differences in persistence to individual NOACs were in line with previous studies, which have demonstrated higher persistence to apixaban than to rivaroxaban or dabigatran ( 8 , 11 , 13 – 15 , 17 , 24 , 34 , 39 , 40 ), except for one study ( 41 ) in which persistence to rivaroxaban was highest. Likewise, other studies also observed predominant switching of dabigatran followed by rivaroxaban ( 30 , 39 – 41 ). Frequent switching and discontinuation of dabigatran may be due to its high dependency on renal clearance, specific side effects such as dyspepsia, longest market approval (resulting in increased switching when other NOACs became available) ( 40 ), twice-daily dosing regimen, and dabigatran being administered in capsules sensitive to moisture which should not be opened or repackaged to other dispensing systems ( 1 , 11 , 18 , 34 , 39 – 42 ).…”

“…Likewise, other studies also observed predominant switching of dabigatran followed by rivaroxaban ( 30 , 39 – 41 ). Frequent switching and discontinuation of dabigatran may be due to its high dependency on renal clearance, specific side effects such as dyspepsia, longest market approval (resulting in increased switching when other NOACs became available) ( 40 ), twice-daily dosing regimen, and dabigatran being administered in capsules sensitive to moisture which should not be opened or repackaged to other dispensing systems ( 1 , 11 , 18 , 34 , 39 – 42 ).…”

“…However, since apixaban and edoxaban have only been available since September 2013 and October 2016 respectively, whereas dabigatran and rivaroxaban since August and September 2012, differences in approval dates may have impacted our results. Physicians may be more familiar and confident with the use of NOACs over time, resulting in less discontinuation ( 15 , 39 ). However, trends were consistent after restricting the study population to subjects having initiated treatment between October 2016 and December 2019, when all NOACs were commercially available in Belgium.…”

Sex and gender differences in the use of oral anticoagulants for non-valvular atrial fibrillation: A population-based cohort study in primary health care in catalonia

“…Also diverse studies, including some conducted by our group ( Giner-Soriano et al, 2016 ; 2020 ; Gomez-Lumbreras et al, 2018 ), have described the clinical profile of OAC-users ( Giner-Soriano et al, 2016 ; Rodríguez-Mañero et al, 2017 ), for instance Rodríguez-Mañero et al described different clinical characteristics and outcomes in octogenarians with AF to those in younger people; the adequacy of the prescription ( Dalmau Llorca et al, 2021 ), reporting inadequate OAC prescriptions in up to 67.6% of the cases; or the adherence and persistence to the treatment, using different methods and finding different compliance levels ( Hurtado-Navarro et al, 2018 ; Banerjee et al, 2020 ; Sabaté et al, 2021 ).…”