Impact of off-label under-dose direct oral anticoagulant on coagulation and fibrinolytic markers in patients with atrial fibrillation

Objectives: Direct oral anticoagulants (DOAC) have been approved for oral anticoagulation in patients with non-valvular atrial fibrillation (AF). On the other hand, DOAC are sometimes prescribed off-label under-doses for patients with AF. This study aimed to compare the effects of different DOAC doses on coagulation and fibrinolytic markers. Methods: A total of 88 patients with AF (age, 68 ± 11 years; male sex, 45%; persistent AF, 43%) were analyzed. All patients received edoxaban (60 or 30 mg) once daily. For this study, patients were divided into three groups according to whether they had been treated before the ablation procedure under an appropriate standard-dose group (n = 30 [34.1%]), appropriate low-dose group (n = 35 [39.8%]), or off-label under-dose group (n = 23 [26.1%]). Coagulation and fibrinolytic markers and echocardiographic parameters were examined before ablation. Results: There were no significant baseline differences in AF type, plasma B-type natriuretic peptide, protein C, fibrinogen, D-dimer level, left ventricular ejection fraction, or left atrial dimension among the three groups. The prothrombin fragment 1+2 (F1+2) level was significantly different among the appropriate standard-dose, appropriate low-dose, and off-label under-dose groups (105.9 ± 29.4, 142.6 ± 41.3, and 142.8 ± 84.9 pmol/L, respectively; P = 0.011). After multivariate analysis, the F1+2 was significantly higher in the off-label low-dose group than in the standard-dose group when compared among the three groups (P = 0.034, Bonferroni test). Conclusion: Our results suggest that an appropriate standard dose of edoxaban is required to suppress hypercoagulability in patients with AF.