Clinical characteristics and outcomes of super-low-dose edoxaban 15 mg compared with reduced dose 30 mg for high-bleeding-risk patients with venous thromboembolism: from the COMMAND VTE Registry-2

Introduction The current guidelines recommend specific durations of anticoagulation therapy depending on the risks of recurrent venous thromboembolism (VTE), and prolonged anticoagulation therapy is recommended for patients at non-low risk of recurrence. However, clinicians are sometimes reluctant to continue anticoagulation therapy for patients with high-bleeding risk. Recently, super-low-dose edoxaban of 15 mg has been reported to be useful for preventing thromboembolic events in elderly patients with atrial fibrillation who were considered as high-bleeding risk patients. However, super-low-dose edoxaban of 15 mg is currently off-label for VTE worldwide and may represent a potential therapeutic option for patients with VTE at high bleeding risk. Purpose The current study aimed to investigate clinical characteristics and outcomes of VTE patients with super-low-dose edoxaban of 15 mg compared with reduced dose of 30 mg for high-bleeding risk patients, using a real-world observational database of patients with VTE in Japan. Methods The COMMAND VTE Registry-2 is a multicenter registry enrolling 5,197 consecutive patients with acute symptomatic VTE from 31 centers in Japan between January 2015 and August 2020. Based on previous studies focusing on fragile patients, high-bleeding risk patients were defined as those with one or more of the following criteria: age ≥ 75 years, body weight ≤ 50 kg, and creatinine clearance ≤ 50 mL/min. After excluding 3,193 patients without edoxaban, 820 patients without high-bleeding risk profile, and 184 patients with edoxaban of 60 mg/day, the current study population consisted of 1,000 high-bleeding risk patients, who were divided into 2 groups according to initial dosage of edoxaban; 15 mg/day (N=28) and 30 mg/day (N=972). Results Patients with edoxaban of 15 mg/day were older (15 mg/day: 82.5 years vs. 30 mg/day: 79.0 years, P=0.02). Pulmonary embolism as initial presentation was less frequent in patients with edoxaban of 15 mg/day (14% vs. 43%, P=0.002). The discontinuation rates of anticoagulation therapy were not significantly different between the 2 groups (59.5% vs. 53.5%, log rank P=0.47). The cumulative 3-year incidences of recurrent VTE were not significantly different between the 2 groups (0% vs. 6.5%, log rank P=0.29). Similarly, the cumulative 3-year incidences of major bleeding were not significantly different between the 2 groups (16.8% vs. 10.8%, log rank P=0.62). The cumulative 3-year incidences of all-cause death were also not significantly different between the 2 groups (31.2% vs. 34.5%, log rank P=0.78). Conclusions In this real-world registry, high-bleeding risk patients with VTE receiving edoxaban of 15 mg/day were markedly older compared with those of 30 mg/day and did not show an apparent signal of increased risk of recurrent VTE, suggesting a potential therapeutic option of anticoagulation therapy for patients with VTE at high bleeding risk.