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

Abstract

Abstract Background Atrial fibrillation (AF) is known to increase the risks of cerebral and systemic embolism. Apart from vitamin K antagonists, edoxaban, a direct oral anticoagulant (DOAC), has been approved for oral anticoagulation in patients with non-valvular AF. On the other hand, DOACs are sometimes prescribed at off-label under-doses for patients who have undergone ablation for AF. Prothrombin fragment F1+2 is an activation peptide released from prothrombin during thrombin formation. The purpose of this study is to compare the effects of DOAC doses on coagulation and fibrinolytic markers. Methods and results A total of 88 patients with AF (age: 68±11 years, male:45%, paroxysmal AF n=49, persistent AF n=39) were recruited. All patients were received edoxaban (60mg or 30mg) once a day. For the purpose of the 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%]). We examined the coagulation and fibrinolytic markers, and echocardiographic parameters before ablation. All patients were followed up for 12 months after AF ablation. Creatinine clearance was significantly higher in appropriate standard-dose group than in appropriate low-dose or off-label under-dose group (101.1±38.4, 57.1±15.9 and 73.2±14.6 mL/min, respectively; P<0.001). There were no significant baseline differences in AF type, history of stroke/transient ischemic attack (TIA), plasma B-type natriuretic peptide, protein C, fibrinogen, D-dimer level, left ventricular ejection fraction or left atrium dimension among the three groups. Prothrombin fragment F1+2 level was significantly lower in the appropriate standard-dose group than the 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, Figure). One patient in the appropriate low-dose group had a TIA and 1 patient in the off-label under-dose group had a bleeding event during the follow up period after ablation. Conclusion Our results suggest that an appropriate standard dose of edoxaban is needed to suppress hypercoagulability in patients with AF. Funding Acknowledgement Type of funding sources: None. Prothrombin fragment F1+2 level