Edoxaban vs. Warfarin in Vitamin K Antagonist Experienced and Naïve AFib Patients | Journal Scan

Study Questions:

What are the efficacy and safety outcomes of edoxaban versus warfarin in patients with and without prior warfarin treatment experience?


The authors performed a subgroup analysis of the ENGAGE AF-TIMI 48 trial, where 21,105 patients with atrial fibrillation (AF) at moderate-to-high risk of stroke were randomized to once-daily edoxaban versus warfarin. Stroke and bleeding outcomes were assessed based on the anticoagulant used (warfarin, lower-dose edoxaban or higher-dose edoxaban) and a patient’s prior warfarin experience (warfarin use for at least 60 days vs. warfarin naïve).


Higher-dose edoxaban significantly reduced the risk of stroke or systemic embolism in warfarin-naïve patients (hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.56-0.90), but had similar efficacy in warfarin-experienced patients (HR, 1.01; 95% CI, 0.82-1.24) as compared to warfarin therapy. Lower-dose edoxaban had similar effects on stroke and systemic embolism in warfarin-naïve patients (HR, 0.92; 95% CI, 0.73-1.15), but was inferior to warfarin in warfarin-experienced patients (HR, 1.31; 95% CI, 1.09-1.60) as compared to warfarin therapy. Both higher-dose and lower-dose edoxaban significantly reduced the risk of major bleeding independent of prior warfarin experience.


The authors concluded that edoxaban appears to have greater efficacy for stroke prevention in AF patients who were warfarin-naïve compared to those who were warfarin-experienced. The authors also concluded that edoxaban reduced the risk of major bleeding compared to warfarin therapy in patients irrespective of their prior warfarin experience.


In a subgroup analysis of the fourth largest randomized controlled trial of a direct oral anticoagulant versus warfarin for stroke prevention in AF, the authors demonstrate that edoxaban’s efficacy for stroke prevention is more pronounced in patients who were warfarin-naïve at the time of randomization compared to warfarin in those who had prior warfarin-treatment experience. This finding was not seen in any of the three prior trials comparing dabigatran, rivaroxaban, or apixaban to warfarin for stroke prevention in AF. This may have occurred due to two unique factors associated with edoxaban: 1) edoxaban’s efficacy at higher levels of renal function (creatinine clearance >95 ml/min) is diminished as compared to warfarin, and 2) unlike dabigatran or rivaroxaban, edoxaban has a lower risk of major bleeding in AF patients as compared to warfarin. It remains to be seen how the unique dosing and efficacy aspects of edoxaban will influence its use for stroke prevention in AF.

Clinical Topics: Anticoagulation Management, Arrhythmias and Clinical EP, Prevention, Anticoagulation Management and Atrial Fibrillation, Implantable Devices, EP Basic Science, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias

Keywords: Anticoagulants, Atrial Fibrillation, Embolism, Stroke, Warfarin, Pyridines, Thiazoles, Primary Prevention, Arrhythmias, Cardiac, Anti-Arrhythmia Agents

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