Prediction of long-term adherence to Direct Oral Anti-Coagulants in patients with Atrial Fibrillation using first-order Markov models

Elias Edward Tannous^1,2*shlomo Selitzky²shlomo Vinker³Nicola Toukan⁴David Stepensky¹Eyal Schwarzberg¹

• ¹Department of Clinical Biochemistry and Pharmacology, School of Public Health, Faculty of Health Sciences, Ben Gurion University of the Negev, Be'er Sheva, Israel
• ²Pharmacy Services, Hillel Yaffe Medical Center, Hadera, Israel
• ³Leumit Health Care Services, Tel Aviv-Yafo, Israel
• ⁴Department of Cardiology, Hillel Yaffe Medical Center, Hadera, Israel

Direct Oral Anti-Coagulants (DOACs) are the primary treatment for the long-term prevention of stroke in patients with atrial fibrillation. Strict adherence to DOAC therapy is crucial and must be maintained over the long term. Therefore, predicting long-term adherence is valuable for identifying patients at risk of non-adherence. We developed a novel method for predicting long-term adherence using first-order Markov models to assess adherence in new DOAC users during years 2-5. The prediction utilized age, CHA2DS2-VASc score, and first-year adherence data as predictors. Adherence was measured by calculating the proportion of days covered within consecutive 90-day windows, which were then stratified into deciles. We subsequently calculated the probability of a patient being in a specific adherence decile. The developed model demonstrated good calibration. We discovered that missing even one day of treatment per month in the first year was predictive of a lower likelihood of achieving the highest adherence decile in years 2-5. Additionally, we noted a non-linear relationship between age and adherence; adherence increased linearly with age but plateaued around age 75. This innovative approach to modelling and predicting adherence to DOACs for long-term therapy can help identify patients at risk of low adherence and may be applicable to other chronic medications.