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

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.

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

“…Aiming for a high adherence to anticoagulants is crucial, as recent studies have shown that the risk of adverse outcomes was lowest in patients with a PDC of ≥ 90% ( 7 , 8 ). Although the observed high adherence to NOACs is in line with previous literature ( 6 , 8 , 10 , 12 , 24 , 34 , 41 ), results on differences in adherence to individual NOACs are more conflicting, with some studies ( 6 , 13 , 24 , 34 ) favoring adherence to once-daily dosed NOACs, whereas other studies ( 7 , 10 , 30 ) described a higher adherence to twice-daily dosed apixaban. However, missing one dose of twice-daily dosed NOACs may not result in a comparably reduced thromboembolic protection as missing one dose of once-daily dosed NOACs, especially since once-daily dosed rivaroxaban and edoxaban actually have the shortest half-lives of NOACs ( 6 , 24 , 46 ).…”

“…The PDC was calculated as the number of days covered with NOAC supply during a time interval, divided by the total number of days of that time interval (PDC range 0–100%). In order to specifically investigate patient-related NOAC adherence at home, only ambulatory prescription claims were considered, consistent with previous studies ( 7 , 10 , 12 ). In case of hospitalization, the length of inpatient stay was deducted from the number of days in the studied time interval ( 7 , 10 , 12 ).…”

“…In order to specifically investigate patient-related NOAC adherence at home, only ambulatory prescription claims were considered, consistent with previous studies ( 7 , 10 , 12 ). In case of hospitalization, the length of inpatient stay was deducted from the number of days in the studied time interval ( 7 , 10 , 12 ). A PDC of < 90% was defined as non-adherence, as higher thromboembolic and mortality risks have been observed in OAC-treated patients with an adherence below 90% ( 7 , 8 , 34 ).…”

Can Machine Learning from Real-World Data Support Drug Treatment Decisions? A Prediction Modeling Case for Direct Oral Anticoagulants

“…Our analysis thus built on already processed data (described in detail elsewhere). 24 In brief, DOAC-naive patients with AF who newly initiated either rivaroxaban or apixaban treatment were followed up from their first DOAC prescription if they met the inclusion criterion of at least 3 follow-up prescriptions and had no exclusion criterion in their medical history. Supplementary Figure S1 depicts the flow of participants and how the study cohort was defined by inclusion and exclusion criteria.…”