Background The introduction of the direct oral anticoagulants (DOACs) widened the options for anticoagulation in atrial fibrillation (AF) and venous thromboembolism. Although they have made anticoagulation more convenient, caution is warranted in patients with renal impairment to decrease bleeding risk as they are partly renally cleared.

Purpose The purpose of this study was to determine the prescribing accuracy of dabigatran etexilate, rivaroxaban and apixaban according to the summaries of product characteristics. Second, bleeding complications or thromboembolic events following inappropriate dosing were investigated. A high rate of dosing errors could lead us to develop clinical decision support systems to prevent such errors.

Material and methods Single-centre, retrospective cohort study conducted in patients≥60 years admitted to UZ Brussel (721-bed university hospital) in 2016 with at least one intake of dabigatran etexilate, rivaroxaban or apixaban. Renal function was estimated using three formulas (Cockcroft–Gault, MDRD and CKD-EPI). Prescribers were divided into interns and non-interns. Statistical differences between groups were evaluated using ANOVA and the Chi Square test.

Results A total of 998 admissions for 777 patients were consequently included. The median CrCl for dabigatran, rivaroxaban and apixaban users was respectively 58, 59 and 54 mL/min: the median eGFR 65.5; 65 and 59 mL/min/1.73 m² (CKD-EPI) (p<0.05). Stroke prevention in AF was the most common indication for all DOACs, with the highest frequency among apixaban users (96.9%). Inappropriate dosing regarding renal function (CrCl), age, weight, serum creatinine and/or indication accounted for 24.8%, 22.3% and 30.3% respectively for dabigatran, rivaroxaban and apixaban (p=0.084). Underdosing was statistically higher for apixaban (84.5%) compared to dabigatran (61.1%) and rivaroxaban (56.2%) (p<0.05). Among the inappropriate doses initiated at the hospital, most of them were started by interns. At least 12 cases with bleeding events were documented while being overdosed. For the underdosed cases, at least three thromoembolic events (two for apixaban and one for rivaroxaban) were retrieved from medical records.

Conclusion Inappropriate dosing was observed among patients with normal and insufficient renal function. Underdosing was mainly seen in apixaban users who form a greater risk to develop thromboembolic events. Further education and development of decision support systems are warranted to increase therapy appropriateness and improve patient safety.

No conflict of interest