New subanalysis data demonstrate edoxaban (Lixana, Daiichi Sankyo) provide comparable efficacy and greater safety compared to warfarin, across non-valvular atrial fibrillation patients with different stroke risk scores. The findings are based on a subanalysis of the ENGAGE AF-TIMI 48 (Effective anticoagulation with factor XA next generation in atrial fibrillation) clinical study and provide more specific insights into the use of oral, once-daily direct factor Xa-inhibitor edoxaban compared to warfarin in non-valvular atrial fibrillation.
The ENGAGE AF-TIMI 48 study has previously shown that once-daily edoxaban is as effective as warfarin for the prevention of stroke or systemic embolic events, while significantly reducing the risk of bleeding. This new subanalysis, which was presented at the European Society of Cardiology (ESC) congress (26–30 August, Barcelona, Spain), has established that the benefit of edoxaban over warfarin is maintained, with no significant effect modification by CHA2DS2-VASc score, which assesses stroke risk more accurately than the previously used CHADS2 score.
Providing insights into edoxaban’s risk-benefit profile in stroke prevention, the subanalysis shows that edoxaban provides an incremental absolute reduction in safety events (including major bleeding, intracranial haemorrhage and cardiovascular hospitalisations) for non-valvular atrial fibrillation patients, over those receiving warfarin, as the risk of stroke increases.
While overall results from ENGAGE AF-TIMI 48 demonstrate that edoxaban provides superior safety for non-valvular atrial fibrillation patients in terms of major bleeding risk compared to warfarin, these data further shows that the safety benefit remains in place in patients with higher CHA2DS2-VASc scores (p-int=0.99 for major bleeding). Major bleeding is a key consideration in assessing appropriate treatment in non-valvular atrial fibrillation, and as such, this data highlights the value of edoxaban for patients at varying levels of stroke risk.
The subanalysis shows that edoxaban provides effective protection against stroke and systemic embolic events, even in patients at high stroke risk. The efficacy of edoxaban compared to warfarin for the prevention of stroke and systemic embolic events is maintained among patients with different CHA2DS2-VASc scores (p-int=0.546 for stroke and systemic embolic events).
Joris De Groot (University of Amsterdam), lead author of the study, says: “These findings can greatly benefit physicians in clinical practice. Reducing stroke risk is paramount to effective non-valvular atrial fibrillation management. The availability of data regarding the use of edoxaban in non-valvular atrial fibrillation management patients of varying levels of stroke risk will help better inform treatment decisions and support treatment assurance for physicians and patients.”