Clinical impact of inappropriate DOAC dosing in atrial fibrillation: insights from a real-world registry

Background. A significant number of patients with atrial fibrillation (AF) on direct oral anticoagulants (DOACs) receives off-label or inappropriate doses. This study examines the prevalence, dosages, and clinical outcomes in AF-patients on DOAC therapy admitted to an emergency department (ED).

Methods. This retrospective single-center observational study utilized data from the Heidelberg Registry of Atrial Fibrillation (HERA-FIB), consecutively including patients with AF presenting to the ED of the University Hospital of Heidelberg from June 2009 to March 2020. Rates of DOAC dosages at discharge from the ED were correlated with outcomes, focusing on a composite endpoint that included all-cause mortality, stroke, major bleeding, and myocardial infarction (MI).

Results. Among 10,222 patients included in the HERA-FIB registry, 4,239 (41.5%) were prescribed DOACs. Of these, 3,031 patients were eligible for the analysis. Among eligible patients, 2,183 (72%) received appropriate dosages, 612 (20.2%) were under-dosed, and 236 (7.8%) were over-dosed. Under-dosed AF-patients demonstrated a significantly increased risk of the composite endpoint compared to those receiving appropriate dosages (HR 1.91, 95% CI 1.38-2.64, p <0.0001). In contrast, DOAC over-dosage was associated with a higher risk of bleeding compared to under-dosage (HR 2.91, 95% CI 1.24-6.85, p=0.01437), without an effect on HR for MI or stroke (p=0.1200 and p=0.8517, respectively).

Conclusion. This study underscores the critical importance of accurate DOAC dosing in patients with AF presenting in the setting of an ED. Both under-dosing and over-dosing are linked to significant clinical risks, highlighting the urgent need for improved dosing protocols and careful monitoring to enhance patient outcomes.