Estimated Thresholds of Minimum Necessary Adherence for Effective Treatment with Direct Oral Anticoagulants – A Retrospective Cohort Study in Health Insurance Claims Data

Lucas Wirbka, Walter Emil Haefeli, Andreas Daniel Meid On behalf of ARMIN Study GroupDepartment of Clinical Pharmacology and Pharmacoepidemiology, University of Heidelberg, Heidelberg, 69120, GermanyCorrespondence: Andreas Daniel MeidDepartment of Clinical Pharmacology and Pharmacoepidemiology, University of Heidelberg, Im Neuenheimer Feld 410, Heidelberg, 69120, GermanyTel +49 6221 56 37113Fax +49 6221 56 4642Email Andreas.Meid@med.uni-Heidelberg.deBackground: 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