https://orcid.org/0000-0003-0672-6876
Abstract
Background
An essential contribution regarding the prevention of thromboembolic events in patients with (non-valvular) atrial fibrillation (AF) is good adherence to direct oral anticoagulants (DOACs). However, it is an open question what “good” adherence means for DOACs or below which threshold non-adherence is clinically relevant for AF patients. Ultimately, such a classification could prevent strokes and associated costs through adjusted treatment regimens or supportive measures.
Methods
We selected 10,092 AF patients from health insurance claims data between 2014 and 2018 who were issued a majority (at least half of the number) of maximum approved strength prescriptions of one of the following DOACs, namely rivaroxaban, apixaban, or dabigatran. Due to the limited sample size, the prescriptions of dabigatran had to be finally excluded for the cut-off analysis. DOAC adherence was calculated as the proportion of days covered (PDC) by dividing the days of theoretical use (days covered) of the drug by the duration in days of the observation interval. PDC cut-off values were derived from stroke risk as a function of continuous PDC values in time-to-event analyses and corresponding dose-response models. The influence of adherence-promoting interventions (targeted and untargeted) on the occurrence of strokes and related costs was then projected, considering intervention costs per patient.
Results
The population had a mean age of 74.5 years and 50% were female. The median PDC was 0.79 ± 0.28 with a median follow-up time of 1218 days, in which 2% of all DOAC patients had a stroke. The adherence cut-offs for good adherence were identified at 0.78 for rivaroxaban and 0.8 for apixaban. Targeted interventions appeared to be far more cost-effective than untargeted interventions.
Conclusion
Clear adherence cut-offs enable healthcare professionals to identify patients with clinically relevant non-adherence. Interventions based on these cut-offs appear to be a promising means to optimize DOAC treatment.
Acknowledgments
Andreas D. Meid is thankful for being supported by the Physician-Scientist Programme of the Medical Faculty of Heidelberg University. We would like to thank Claudia Marquart for her expert assistance with the linguistic revision of the manuscript.
The ARMIN study group: Christiane Eickhoff, Uta Mueller, Martin Schulz (ABDA – Federal Union of German Associations of Pharmacists, Berlin); Andreas Fuchs, Dorit Braun, Ulf Maywald (AOK PLUS, Dresden); Catharina Doehler, Mike Maetzler (Association of Statutory Health Insurance Physicians – Saxony, Dresden); Anja Auerbach, Urs Dieter Kuhn, Anke Moeckel (Association of Statutory Health Insurance Physicians – Thuringia, Weimar); Christine Honscha, Susanne Donner (State Association of Pharmacists – Saxony, Leipzig); Stefan Fink, Kathrin Wagner (State Association of Pharmacists – Thuringia, Erfurt); Andreas D. Meid, Robert Moecker, Carmen Ruff, Hanna M. Seidling, Felicitas Stoll, Marina Weissenborn, Lucas Wirbka (Heidelberg University Hospital, Heidelberg).
Disclosure
Lucas Wirbka is funded by the German Innovation Funds according to § 92a (2) Volume V of the Social Insurance Code (§ 92a Abs. 2, SGB V - Fünftes Buch Sozialgesetzbuch), grant number: 01VSF18019. Andreas D. Meid is funded by the Physician-Scientist Programme of the Medical Faculty of Heidelberg University. The funding bodies did not play any role in the design of the study and data collection, analysis, and interpretation of data, and in writing the manuscript. Prof. Dr. Walter E Haefeli report grants, personal fees from Daiichi-Sankyo, outside the submitted work. The authors report no other conflicts of interest in this work.