Abstract 12680: Efficacy and Safety of Edoxaban Compared With Warfarin in Patients With Atrial Fibrillation and Heart Failure: Insights From Engage-AF TIMI 48

Abstract

BACKGROUND: Atrial fibrillation (AF) and heart failure (HF) have emerged as the two epidemics of cardiovascular (CV) disease. The prevalence of AF increases with the severity of HF and contributes to HF disability. Among patients treated with vitamin K antagonists (VKAs), symptomatic HF is an independent risk factor for lower time in therapeutic range (TTR), which reduces the efficacy and safety of VKAs. METHODS: In the ENGAGE AF-TIMI 48 trial, both once-daily regimens of the direct oral factor Xa inhibitor edoxaban [high (HDE) and low dose (LDE)], were non inferior to warfarin (W) for prevention of stroke and systemic embolic events (SEE) in patients with AF and were associated with lower rates of bleeding. We evaluated the safety and the efficacy of edoxaban compared with W in patients with HF presenting with different severity of functional limitation (NYHA class). RESULTS: Among 21,105 patients enrolled 8,981(43%) had no history of HF, 9,489 (45%) had history of HF and a NYHA class I-II, whereas 2,635 (13%) had symptomatic HF with NYHA class III-IV. Patients with more severe HF symptoms had higher rates of stroke SEE, CV death and CV hospitalization (p<0.0005 for all) and among those treated with W we observed a lower mean TTR (62.6% vs. 70.0%, p<0.001). Compared with W, the efficacy of both edoxaban doses in reducing stroke or SEE was similar between patients with and without HF (HDE vs. W, p int=0.96; LDE vs. W, p int=0.63, Fig.) and there were no differences between NYHA classes. CV hospitalization was significantly reduced with HDE relative to W, without heterogeneity by different NYHA classes (p int=0.5, Fig.). Both edoxaban regimens reduced consistently major bleeding and intracranial hemorrhage, regardless of HF severity (Fig.). CONCLUSION: The relative efficacy and safety of both edoxaban regimens, compared to well-managed W in AF patients with HF, was consistent irrespective of the severity of functional class.