OBJECTIVES: Direct oral anticoagulants (DOACs) play an essential role in the pharmacotherapy of atrial fibrillation (AF) for preventing cardiovascular complications. However, poor adherence to DOACs is a major concern due to the elevated risk of stroke and mortality. This study aimed to investigate the association between adherence to DOACs and the risk of stroke, systemic embolism, and acute coronary syndrome (ACS) using a marginal structural model (MSM).

METHODS: This retrospective cohort study was conducted using Texas Medicare Advantage Plan data from January 2016-December 2020. Patients with AF were included if they received any DOAC (between July 2016-December 2017) and were continuously enrolled in the plan throughout the study. The follow-up period was started from the index date (first DOAC fill) and divided into 6-monthly intervals and 4 time periods (T1-T4). Adherence to DOACs was the time-varying exposure and was measured during 6-monthly intervals using proportion of days covered. Composite events (stroke, systemic embolism, ACS) were the outcome of the study and were identified for each of the four time periods using ICD-10 codes. A MSM was conducted to estimate the association between adherence and composite events by controlling for time dependent variables and other covariates.

RESULTS: A total of 1,969 AF patients were included in the study with majority using rivaroxaban (55.8%) and apixaban (38%). Adherence was suboptimal with declining patterns over the 6-monthly intervals, ranging from 53.1% to 39.8%. MSM results showed that adherence to DOACs was not significantly associated with the incidence of composite events (OR:1.17 [95% CI: 0.86-1.58]).

CONCLUSIONS: This study revealed that although adherence to DOACs declined over time in AF patients, the incidence of composite events was comparable among the adherent and nonadherent patients. Future studies should explore the association between adherence to DOACs and health outcomes for a longer duration of follow-up using MSM.