Key result
Edoxaban matches warfarin for preventing ischemic stroke and reduces CV death ~12% in AF.
Why the study?
It was unclear whether the advantages of edoxaban over warfarin remain consistent across different AF patient subgroups with distinct clinical phenotypes and interventions.
Does edoxaban improve outcomes compared to warfarin in patients with atrial fibrillation with different clinical phenotypes?
Meta-Analysis
Does edoxaban improve outcomes compared to warfarin in patients with atrial fibrillation with different clinical phenotypes?
Effect estimate: RR 0.98 (95% CI 0.83-1.16)
p-value: p=0.81
Edoxaban provides consistent efficacy for stroke prevention and reduces cardiovascular death and ICH compared to warfarin across various AF phenotypes, though bleeding risk may be higher in TAVI patients.
Edoxaban matches warfarin for stroke prevention with CV death reduction; confirms benefit across AF phenotypes.
Background Patients with atrial fibrillation (AF) may exhibit different clinical phenotypes and receive various interventions, such as percutaneous coronary intervention (PCI) for coronary artery disease, catheter ablation, and transcatheter aortic valve implantation (TAVI) for aortic stenosis. These patients may differ significantly in clinical characteristics and outcomes. Therefore, whether the advantages of edoxaban over warfarin remain consistent across these patient subgroups is unclear. In this study, we conducted a meta-analysis of randomized controlled trials (RCTs) to investigate this issue. Methods We systematically searched the literature for randomized clinical trials comparing edoxaban to warfarin in AF patients. Results A total of five randomized trials were identified, including ENSURE-AF (AF patients undergoing electrical cardioversion), ENTRUST-AF PCI, ENGAGE AF-TIMI 48, ENVISAGE-TAVI AF, and ELIMINATE-AF (AF patients undergoing catheter ablation). Edoxaban was found to be as effective as warfarin in preventing ischemic stroke, with a relative risk (RR) of 0.98 (95% confidence interval [CI] 0.83–1.16; p = 0.81), and no significant heterogeneity was observed between the different trials (Figure 1). Compared to warfarin, edoxaban reduced the risk of cardiovascular death by 12% (RR 0.88, 95% CI 0.79–0.98; p = 0.02) (Figure 1). For the safety endpoint, the risk of major bleeding was similar between edoxaban and warfarin (RR = 1.01, p = 0.97)(Figure 2). However, significant heterogeneity was observed, as edoxaban reduced the risk of major bleeding by 20% (RR 0.80, 95% CI 0.70–0.90) in the ENGAGE AF-TIMI 48 trial but increased the risk by 44% (RR 1.44, 95% CI 1.08–1.93) in the ENVISAGE-TAVI AF trial. In contrast, edoxaban consistently reduced the risk of intracranial hemorrhage (ICH) by 48% (RR 0.52, 95% CI 0.37–0.74) across different trials without significant heterogeneity (p = 0.38)(Figure 2). Conclusions This meta-analysis suggests that edoxaban is as effective as warfarin for stroke prevention while reducing the risks of cardiovascular death and ICH across different trials without significant heterogeneity. However, AF patients with aortic stenosis undergoing TAVI may represent a unique subgroup that requires further research to determine the optimal antithrombotic strategy.
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Chao et al. (2025) conducted a meta-analysis in Atrial fibrillation. Edoxaban vs. Warfarin was evaluated on Ischemic stroke (RR 0.98, 95% CI 0.83-1.16, p=0.81). Edoxaban was as effective as warfarin in preventing ischemic stroke (RR 0.98; 95% CI 0.83-1.16) and reduced cardiovascular death by 12% (RR 0.88; 95% CI 0.79-0.98) in patients with atrial fibrillation.
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