Lixiana is indicated in:
- Prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation with one or more risk factors (such as congestive heart failure, hypertension, age ≥75 years, diabetes, prior stroke or transient ischaemic attack)
- Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE)
- Prevention of recurrent DVT and PE
In a randomised, double-blind, double-dummy trial (ENGAGE-AF-TIMI), high- and low-dose edoxaban regimens (60mg and 30mg once daily) were tested for non-inferiority to warfarin in patients with moderate- to high-risk atrial fibrillation (n=21,105). The principal safety endpoint was major bleeding.
During the treatment period, a stroke or systemic embolic event occurred in 232 patients in the warfarin group compared with 182 patients in the high-dose edoxaban group (1.50% vs 1.18%, hazard ratio 0.79, 97.5% CI 0.63–0.99; p<0.001 for non-inferiority) and 253 patients (1.61%) in the low-dose edoxaban group (hazard ratio 1.07, 97.5% CI 0.87–1.31; p=0.005 for non-inferiority).
The annualised rate of major bleeding was 3.43% with warfarin versus 2.75% with high-dose edoxaban and 1.61% with low-dose edoxaban (p<0.001 for both doses vs warfarin). The annualised rates of death from cardiovascular causes were 3.17% for warfarin versus 2.74% (hazard ratio 0.86, 95% CI 0.77–0.97; p=0.01) and 2.71% (hazard ratio 0.85, 95% CI 0.76–0.96; p=0.008) for high- and low-dose edoxaban respectively.
The investigators concluded that both edoxaban regimens were non-inferior to warfarin with respect to prevention of stroke or systemic embolism. Edoxaban was also associated with significantly lower rates of bleeding and death from cardiovascular causes than warfarin.
A second randomised, double-blind, non-inferiority study (Hokusai-VTE) examined the use of edoxaban and warfarin in patients with DVT or PE.
Treatment with edoxaban or warfarin was continued for at least 3 months in all patients and for a maximum of 12 months, with the duration based on patients’ clinical features and preference.
Recurrence of venous thromboembolism occurred in 130 of 4118 patients (3.2%) in the edoxaban group and in 146 of 4122 patients (3.5%) in the warfarin group (hazard ratio 0.89, 95% CI 0.70−1.13; p<0.001 for non-inferiority). The difference in risk (edoxaban minus warfarin) was −0.39 percentage points (95% CI −1.16 to 0.39).
Rates of major or clinically relevant non-major bleeding were significantly lower with edoxaban than warfarin (8.5% vs 10.3%; hazard ratio 0.81, 95% CI 0.71–0.94; p=0.004 for superiority).
The finding showed that edoxaban was non-inferior to warfarin therapy and caused significantly less bleeding in a broad spectrum of patients with venous thromboembolism.
As with all anticoagulants, bleeding is a risk in patients taking edoxaban and should be monitored. Anaemia may also occur, as well as skin reactions and altered liver function tests.
Draft NICE recommendation
NICE has issued a Final Appraisal Determination recommending edoxaban as an option for the treatment and prevention of recurrent DVT and PE in adults.