Inappropriate dose of nonvitamin-K antagonist oral anticoagulants: prevalence and impact on clinical outcome in patients with nonvalvular atrial fibrillation

Abstract

Background Limited real-world data are available regarding the outcome of patients treated with inappropriate dose of nonvitamin-K antagonist oral anticoagulants (NOACs). Objective To assess the prevalence and factors associated with inappropriate dose prescription of NOACs and to evaluate adverse events that come from this inappropriate prescription. Methods Single-center multidisciplinary registry including nonvalvular atrial fibrillation patients treated with NOACs. Based on guidelines criteria for dose reduction, two subcohorts were defined as treated with appropriate or inappropriate NOACs dose. Primary efficacy endpoint was 2-year rate of thromboembolic events. Primary safety endpoint was 2-year rate of major bleeding. Event-free survival curves among groups were compared using Cox–Mantel test. Results A total of 760 nonvalvular atrial fibrillation patients were included; 32% patients were treated with dabigatran, 34% with apixaban, 24% with rivaroxaban and 10% with edoxaban. An inappropriate dose was prescribed in 96 patients (12.6%), and in most cases (68%) it was too low. Rivaroxaban (15%) and apixaban (18.5%) were the most frequently prescribed with an inappropriate dose. Patients treated with an inappropriate dose were elderly people, with low-creatinine clearance value, who had experienced previous bleeding and with a high CHADS2 VASc score. In 2 years, a trend for higher numbers of thromboembolic events (5.2 vs. 3.3%, P = 0.348) and less major bleeding (2.1 vs. 4.2%, P = 0.316) has been observed in patients with inappropriate NOACs prescriptions. Conclusion Nearly 13% of patients were treated with an inappropriate dose of NOACs, in this single-center study. A trend for higher numbers of thromboembolic events was observed in these patients. The results should be considered as hypothesis generating.

Assessment of treatment patterns and patient awareness in atrial fibrillation patients using non-vitamin K antagonist oral anticoagulants (ASPECT-NOAC)

“…Inappropriate dosing of NOACs has been associated with increased thromboembolism and mortality in AF patients [21] , [22] , [23] (Godino2020, Camm2020, Steinberg2018). In accordance with these publications, we found that the rate of undertreatment with NOACs was higher in the deceased.…”

Impact of Weight on Clinical Outcomes of Edoxaban Therapy in Atrial Fibrillation Patients Included in the ETNA-AF-Europe Registry

“…Inappropriate dosing is not uncommon with NOACs. Use of off-label dosing regimen may be influenced by various factors including clinician perception of higher bleeding risk and lack of familiarity with dosing guidelines [19,20]. More commonly, inappropriate low dosing has been reported in studies exploring daily practice of NOACs [21,22].…”

Effectiveness and safety of dabigatran compared to vitamin K antagonists in patients with atrial fibrillation: a systematic review and metanalysis.

“…In contrast to the other DOACs, in which dose adjustment was performed in the phase III clinical trials, in RE-LY, patients were randomized to receive either dabigatran 150 mg or 110 mg, but no dose adjustment was required [8,[46][47][48]. A great concern with DOACs is the prescription of inappropriate doses that could translate into more events [49]. However, our study showed that in clinical practice, both doses of dabigatran seem effective and safe.…”