Abstract

<h3>BACKGROUND</h3> Medication taking is a dynamic behavior that changes over time. Conventional adherence summary measures (e.g. proportion days covered) used in the OAC adherence studies conducted so far, however, are insensitive to the fluid nature of adherence. For example, identical PDC values can be calculated for patients with initial good adherence followed by poor adherence, and for those with periodic nonadherence throughout the course of therapy. The objective of this study was to characterise atrial fibrillation (AF) patients' long-term unique oral anticoagulant (OAC) adherence trajectories. <h3>METHODS AND RESULTS</h3> Using linked, population-based administrative data containing physician billings, hospitalization and prescription records of 4.8 million British Columbians (1996-2019), incident adult cases of AF were identified. Only patients who had prescription refill data available for five years were included in the analysis. The primary measure of OAC adherence was the proportion of days covered (PDC) over consecutive 90-day rolling windows. We modeled continuous 90-day PDC values over time. The time variable was number of years since OAC initiation. Group-Based Trajectory Modeling (GBTM) was used to identify patients' unique longitudinal adherence trajectories. To determine the best model, a relative comparison was done between models using Bayesian information criteria (BIC), and the Akaike information criterion (AIC). The study cohort was 19,749 AF patients [mean age 70.6y (SD 10.64), 56% male, mean CHA2DS2-VASc score 2.77 (SD 1.39]. The model that best fit our data identified four distinct OAC adherence trajectories. These were "consistent good adherence" (n=14,631 patients, 74.1% of the cohort), "rapid decline and discontinuation" (n=2327, 11.8%), "rapid decline with recovery"(n=1973, 9.99%), and "slow decline and discontinuation" (n=819, 4.2%). Our results show that there is heterogeneity among non-adherers. PDC dropped significantly in the first year after therapy initiation for those with "rapid decline and discontinuation" trajectory. Patients exhibiting "rapid decline with recovery" also displayed a rapid decline in adherence in the first year but showed improvements around the third year. Those in the "slow decline and discontinuation" trajectory displayed slow decline in adherence over first three years which eventually led to permanent discontinuation of therapy. <h3>CONCLUSION</h3> In this retrospective study we distinguished between the different kinds of non-adherence in terms of timing and rate. While a majority of our cohort adhered to their medications, we identified three unique trajectories displaying declining adherence over time at varying rates. Our results emphasize the importance of early intervention and have direct implications for improving the design of adherence interventions.

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