Increasing Very Low-Dose Edoxaban Prescription: Effectiveness and Safety Data of Korean AF Patients

Abstract

Background and objectives: Evidence remains limited on the real-world prescription of very low-dose oral anticoagulation among frail patients with atrial fibrillation (AF). We described the practice patterns, effectiveness, and safety of very low-dose edoxaban (15 mg once daily).

Methods: Patients with AF prescribed edoxaban 15 mg once daily in 2 tertiary hospitals between 2016 and September 2022 were included. Baseline clinical characteristics and clinical outcomes of interest were thromboembolic and bleeding events.

Results: A total of 674 patients were included (mean age 78.3±9.1, 49.7% aged ≥80 years, 49.3% women, median follow-up 1.0±1.2 years). Mean CHA₂DS₂-VASc score was 3.9±1.6, and the modified HAS-BLED score was 2.0±1.1. Between 2016 and 2022, the number of very low-dose edoxaban prescriptions increased. The main reasons for the prescription of very low-dose were low body weight (55.5% below 60 kg), anaemia (62.8%), chronic kidney disease (40.2%), active cancer (15.3%), concomitant anti-platelet use (26.7%), and prior major bleeding (19.7%). During a median follow-up duration of 8 (interquartile range 3-16) months, overall thromboembolic and bleeding events occurred in 16 (2.3%) and 88 (13.1%) patients, respectively. Compared to the expected event rates on the established risk scoring systems, patients receiving very low-dose edoxaban demonstrated a 61% reduction in ischemic stroke, a 68% reduction of ischemic stroke/transient ischemic attack/systemic embolism, whereas a 49% increase in major bleeding.

Conclusions: The prescription of very low-dose edoxaban was increased over time, attributable to various clinical factors. The use of very low-dose edoxaban reduced the expected risk of thromboembolic events.

Keywords: Atrial fibrillation; Bleeding; Factor Xa inhibitor; Off-label use; Stroke.

Figure 1. Study flow. Total 674 patients who were prescribed edoxaban 15 mg once daily for stroke prevention in AF was enrolled from SNUH and AMC.

AF = atrial fibrillation; AMC = Asan Medical Center; SNUH = Seoul National University Hospital.

Figure 2. The temporal trend of edoxaban 15 mg prescription. The prescription of very low-dose edoxaban increased over time in Korea, with a substantial rise observed after landmark events.

AF = atrial fibrillation; ELDERCARE-AF = Edoxaban Low-Dose for Elder Care Atrial Fibrillation Patients; KFDA = Korean Food and Drug Administration; KHRS = Korean Heart Rhythm Society; RCT = randomized clinical trial.

Figure 3. Expected risk versus actual rate. Based on the CHA₂DS₂-VASc score, the RRR for ischemic stroke was 61%, and 68% for stroke/TIA/SE. According to the modified HAS-BLED score, there was a 49% increase in the relative risk of major bleeding.

RRI = relative risk increase; RRR = relative risk reduction; SE = systemic embolism; TIA = transient ischemic attack. ^*Modified HAS-BLED score used.

Figure 4. In Korean practice, very low-dose edoxaban increased over time with low body weight, anaemia, chronic kidney disease, active cancer, concomitant antiplatelet agents, and prior major bleeding as the main cause. The use of very low-dose edoxaban reduced the expected risk of thromboembolic events.

AF = atrial fibrillation; AMC = Asan Medical Center; ELDERCARE-AF = Edoxaban Low-Dose for Elder Care Atrial Fibrillation Patients; KFDA = Korean Food and Drug Administration; KHRS = Korean Heart Rhythm Society; SE = systemic embolism; SNUH = Seoul National University Hospital; TIA = transient ischemic attack.