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

M Sabaté; X Vidal; E Ballarin; M Rottenkolber; S Schmiedl; B Grave; C Huerta; E Martin-Merino; D Montero; L M Leon-Muñoz; C Gasse; N Moore; C Droz; R Lassalle; M Aakjær; M Andersen; M L De Bruin; P Souverein; O H Klungel; H Gardarsdottir; L Ibáñez

doi:10.3389/fphar.2021.682890

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

Front Pharmacol. 2021 Nov 3:12:682890. doi: 10.3389/fphar.2021.682890. eCollection 2021.

Authors

M Sabaté^{1

2

3}, X Vidal^{1

2

3}, E Ballarin^{1

2}, M Rottenkolber⁴, S Schmiedl^{5

6}, B Grave⁷, C Huerta⁸, E Martin-Merino⁸, D Montero⁸, L M Leon-Muñoz⁸, C Gasse⁹, N Moore¹⁰, C Droz¹⁰, R Lassalle¹⁰, M Aakjær¹¹, M Andersen¹¹, M L De Bruin¹², P Souverein¹³, O H Klungel^{13

14}, H Gardarsdottir^{13

15

16}, L Ibáñez^{1

2

3}

Affiliations

¹ Fundació Institut Català de Farmacologia (FICF), Barcelona, Spain.
² Department of Clinical Pharmacology, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
³ Department of Pharmacology, Toxicology and Therapeutics, Universitat Autònoma de Barcelona, Barcelona, Spain.
⁴ Diabetes Research Group, Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany.
⁵ Department of Clinical Pharmacology, School of Medicine, Faculty of Health, Witten/Herdecke University, Witten, Germany.
⁶ Philipp Klee-Institute for Clinical Pharmacology, Helios University Hospital Wuppertal, Wuppertal, Germany.
⁷ AOK NORDWEST, Dortmund, Germany.
⁸ Pharmacoepidemiology and Pharmacovigilance Division, Spanish Agency of Medicines and Medical Devices (AEMPS), Madrid, Spain.
⁹ Aarhus University, Aarhus, Denmark.
¹⁰ Bordeaux PharmacoEpi, INSERM CIC1401, Université de Bordeaux, CHU de Bordeaux, Bordeaux, France.
¹¹ Pharmacovigilance Research Centre, Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
¹² Copenhagen Centre for Regulatory Science (CORS), Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
¹³ Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Universiteit Utrecht, David de Wiedgebouw, Utrecht, Netherlands.
¹⁴ Julius Center, University Medical Center Utrecht, Utrecht, Netherlands.
¹⁵ Department of Clinical Pharmacy, University Medical Center Utrecht, Utrecht, Netherlands.
¹⁶ Faculty of Pharmaceutical Sciences, University of Iceland, Reykjavik, Iceland.

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).

Keywords: adherence; anticoagulants; cardiovascular; drug utilization; europe; non valvular atrial fibrillation; persistence; pharmacoepidemiology.

Copyright © 2021 Sabaté, Vidal, Ballarin, Rottenkolber, Schmiedl, Grave, Huerta, Martin-Merino, Montero, Leon-Muñoz, Gasse, Moore, Droz, Lassalle, Aakjær, Andersen, De Bruin, Souverein, Klungel, Gardarsdottir and Ibáñez.