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

Abstract

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).

Resultsand conclusions: Among 10,222 patients included in the HERA-FIB registry, 4,239 (41.5 %) were prescribed DOACs, and 3,031were eligible for the analysis. Of these, 2,199 (72.6 %) received appropriate dosages, 627 (20.7 %) were under-dosed, and 205 (6.8 %) were over-dosed. Under-dosed AF-patients demonstrated a significantly increased risk of the composite endpoint compared to those receiving appropriate dosages (HR 1.84, 95 %CI:1.55-2.18, p < 0.0001). Over-dosage had no significant effect on the HR for the composite endpoint, all-cause mortality, stroke, MI, or major bleeding compared to correct dosing but was associated with higher risks of the composite endpoint (HR 1.43, 95 %CI:1.04-1.96, p = 0.029) relative to under-dosage. This study underscores the critical importance of accurate DOAC dosing in patients with AF presenting to 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.

Keywords: Atrial fibrillation; Direct oral anticoagulants; Real-world evidence; Registry.

Fig. 1

Patient recruitment and selection flow diagram. This flow diagram illustrating the recruitment and selection process for study participants, including the applied inclusion and exclusion criteria. Abbreviations: AF, atrial fibrillation; CPU, chest pain unit; DOAC, direct oral anticoagulants.

Fig. 2

Changes in oral anticoagulant (OAC) regimens during ED visits. This figure depicts the distribution of oral anticoagulant (OAC) use among patients at admission to the ED and at discharge from the ED. The graph illustrates the changes in OAC use over the course of the ED visit. Abbreviations: ED, emergency department; OAC, oral anticoagulation; VKA, vitamin K antagonist.

Fig. 3

Impact of DOAC dosage accuracy on clinical outcomes. This figure presents a forest plot summarizing the hazard ratios (HRs) and their 95% confidence intervals (CIs) for clinical outcomes, including all-cause mortality, stroke, major bleeding events, myocardial infarction, and a composite endpoint, in relation to the accuracy of direct oral anticoagulant (DOAC) dosing. The plot visually compares the risk of these events across different levels of DOAC dosage accuracy.

Fig. 4

Kaplan-Meier curves for composite endpoint by DOAC dosage. This figure depicts Kaplan-Meier curves illustrating the survival differences over time among patients receiving direct oral anticoagulants (DOACs) with varying levels of dosage accuracy for the composite endpoint. The curves demonstrate that under-dosed patients have the poorest survival outcomes, followed by over-dosed patients, while correctly dosed patients exhibit the best survival.