Efficacy and Safety of Edoxaban Compared to Warfarin According to the Burden of Diseases in Patients with Atrial Fibrillation: Insights from the ENGAGE AF-TIMI 48.

INTRODUCTION: Non-vitamin K antagonist oral anticoagulants represent a new option for prevention of embolic events in patients with atrial fibrillation (AF). However, little is known about the impact of non-cardiac comorbidities on the efficacy and safety profile of these drugs. METHODS: In a post-hoc analysis of the ENGAGE AF-TIMI 48 trial, we analyzed 21,105 patients with AF followed for an average of 2.8 years and randomized to either a higher-dose edoxaban regimen (HDER), a lower-dose edoxaban regimen (LDER), or warfarin. We used the Updated Charlson Comorbidity Index (CCI) to stratify the patients according to the burden of concomitant disease (CCI=0, 1, 2, 3 and ≥4). The treatment groups were then compared for safety, efficacy, and net clinical outcomes across CCI categories. RESULTS: There were 32.0%, 7.3%, 42.1%, 12.7%, and 6.0% of patients with CCI scores of 0, 1, 2, 3, and ≥4, respectively. A CCI score ≥4 was associated with significantly higher rates of thromboembolic events, bleeding, and death compared to CCI=0 (P  0.10 for each). CONCLUSIONS: Although increasing CCI scores are associated with worse outcomes, the efficacy, safety, and net clinical outcomes of edoxaban vs warfarin were independent of the degree of comorbidity present.