Determinants of Inappropriate Dosing of Direct Oral Anticoagulants in Non-Valvular Atrial Fibrillation in a Low-Income Country

Abstract

Introduction The appropriate use of direct oral anticoagulants (DOACs) is crucial in patients with non-valvular atrial fibrillation (NVAF) to prevent thromboembolic complications. The use of inappropriate doses is common, but information on its prevalence and determining factors in low-income countries is insufficient. Objective The objective of this study is to quantify the prevalence and identify demographic, clinical, and treatment-related factors associated with inappropriate dosing of DOACs in patients with NVAF in a low-income country. Methods A retrospective and observational study was conducted from June 2023 to July 2024 at the Dominican Institute of Cardiology Association. Outpatients over 18 years of age with a diagnosis of NVAF and treatment with DOACs were included and classified into two groups based on dose appropriateness. Univariate analyses, such as chi-square and Student's t-tests or Mann-Whitney U tests, were used, along with a multivariate logistic regression analysis, to adjust for potential confounding factors. Results In a study involving 392 patients with NVAF treated with DOACs, 72.19% (283 patients) received appropriate doses, whereas 27.81% (109 patients) were dosed inappropriately. Specifically, 15.56% were underdosed and 12.24% were overdosed. Among the 268 patients prescribed apixaban, 71.64% received an appropriate dose, whereas 28.36% were prescribed an inappropriate dose, with 80.26% of these cases involving low doses. Furthermore, a significantly greater proportion of these patients received apixaban at a reduced dose of 2.5 mg every 12 hours (p<0.001). In contrast, 73.39% of the 124 patients on rivaroxaban had appropriate dosing, but 26.61% were dosed inappropriately, all of which were overdoses. Patients who received inappropriate dosing were older (79.22 vs. 76.06 years; p=0.006), had higher serum creatinine levels (1.23 vs. 1.1 mg/dL; p=0.004), and had lower creatinine clearance (39.38 vs. 51.69 mL/min; p<0.001). The prevalence of vascular disease (15.60% vs. 7.77%; p=0.02) and anemia (7.34% vs. 1.77%; p=0.01) was also higher in this group. Multivariate analysis identified advanced age (OR=1.04; 95% CI: 1.01-1.06; p=0.006), vascular disease (OR=2.28; 95% CI: 1.11-4.67; p=0.024), and elevated creatinine levels (OR=2.00; 95% CI: 1.1-3.63; p=0.024) as significant predictors of inappropriate dosing. Conclusion The study found that 27.81% of patients with NVAF received inappropriate DOACs doses, primarily due to underdosing. Significant factors associated with dosing inadequacy included advanced age, reduced creatinine clearance, and vascular disease.

Keywords: atrial fibrillation; direct oral anticoagulant; inappropriate dosing; inappropriate prescribing; low-income country.

Figure 1. Distribution of patients on DOACs according to dose appropriateness.

The pie chart illustrates the proportion of patients who received appropriate, inappropriately low, or inappropriately high doses of DOACs. DOAC, direct oral anticoagulant