METHODS: Medline, Embase and Web of Science were searched to March 8, 2014 for prospective, randomized controlled trials (RCTs) that assessed the safety profile of
edoxaban with
warfarin. Safety outcomes examined included
bleeding risk and mortality.
RESULTS: Five trials including 31,262 patients that met the inclusion criteria were pooled. Overall,
edoxaban was associated with a significant decrease in major or clinically relevant nonmajor
bleeding events [risk ratio (RR) 0.78, 95% confidence interval (CI) 0.74 to 0.82, p<0.001] and any
bleeding events [RR 0.82, 95% CI 0.79 to 0.85, p<0.001].
Edoxaban also showed superiority to
warfarin both in all-cause mortality [RR 0.92, 95% CI 0.85 to 0.99, p = 0.02] and cardiovascular mortality [RR 0.87, 95% CI 0.79 to 0.96, p = 0.004]. Subgroup analyses indicated that RRs of
edoxaban 30, 60 or 120 mg/d were 0.67 (p<0.001), 0.87 (p<0.001) and 3.3 (p = 0.004) respectively in major or clinically relevant nonmajor
bleeding; 0.71 (p<0.001), 0.89 (p<0.001) and 2.29 (p = 0.002) respectively in any
bleeding; as well as 0.86 (p = 0.01), 0.87 (p = 0.01) and 0.28 (p = 0.41) respectively in cardiovascular death… Meanwhile, paramount to note that pooled results other than the largest trial showed
edoxaban was still associated with a decrease in the rate of major or clinically relevant nonmajor
bleeding event (p = 0.02) and any
bleeding (p = 0.002), but neither in all-cause death (p = 0.66) nor cardiovascular death (p = 0.70).
CONCLUSIONS:
Edoxaban, a novel orally available
direct factor Xa inhibitor, seems to have a favorable safety profiles with respect to
bleeding risk and non-inferior in mortality when compared to
warfarin. Further prospective RCTs are urgently needed to confirm the results of this meta-analysis.