Key result
Edoxaban significantly reduced the risk of major or clinically relevant nonmajor bleeding events (RR 0.78) and all-cause mortality (RR 0.92) compared to warfarin.
Why the study?
Does edoxaban reduce bleeding risk and mortality compared to warfarin?
Meta-Analysis (n=31,262)
Double-blind
Yes
Yes
Does edoxaban reduce bleeding risk and mortality compared to warfarin?
Relative Risk: 0.78 (95% CI 0.74–0.82)
p-value: p=<0.001
Edoxaban demonstrates a favorable safety profile with reduced bleeding risk and lower all-cause mortality compared to warfarin.
Supports preferring edoxaban over warfarin to reduce bleeding and mortality; confirms benefits in pooled trial data.
OBJECTIVE(S): Edoxaban, a factor Xa inhibitor, is a new oral anticoagulant that has been developed as an alternative to vitamin K antagonists. However, its safety remains unexplored. 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.
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Li et al. (2014) conducted a meta-analysis in Nonvalvular atrial fibrillation, deep vein thrombosis, or pulmonary embolism (n=31,262). Edoxaban vs. Warfarin was evaluated on Major or clinically relevant nonmajor bleeding events (RR 0.78, 95% CI 0.74-0.82, p=<0.001). Edoxaban significantly reduced the risk of major or clinically relevant nonmajor bleeding events (RR 0.78) and all-cause mortality (RR 0.92) compared to warfarin.
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