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
D Baba, Y Yamashita, M Oi, Y Kobayashi, R Chatani, K Kaneda, Y Nishimoto, N Ikeda, R Nishikawa, K OnoAbstract
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.Major bleeding KMFor image description, please refer to the figure legend and surrounding text.Recurrence KMFor image description, please refer to the figure legend and surrounding text.