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

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.