Abstract 18342: Post Discharge and Early Clinical Benefits of Eplerenone in Patients With Systolic Nyha Ii Heart Failure: Insight From Emphasis-hf

Purpose: Patients with heart failure (HF) have a high adverse event rate in the early post-discharge period after hospitalization for HF. No treatment initiated during this period is proven to improve outcome. In EMPHASIS-HF, which evaluated the impact of eplerenone (epl) in patients with HF with reduced ejection fraction (HFrEF) and mild symptoms, most participants were included within 180 days following a cardiovascular hospitalization (CVH). We examined the effect of eple on outcomes early after hospital discharge. Methods: In EMPHASIS-HF, eple was compared to placebo (pbo) in 2737 patients with NYHA class II HF and LVEF ≤35%. In a first post-hoc analysis in 2338 patients randomized within 180 days of a CVH, we assessed the interaction between the time from index CVH to randomization and the primary outcome of CV death or HF hospitalization (HHF) using multivariable Cox survival models. In a second analysis, the effect of epl on 30-day outcome was assessed in the complete cohort. Results: The most common reason for CVH within 180 days was HHF (N=1496, 64.0%). The median time from index CVH to randomization was 42 days. In the <42 days group, median time from the index CVH was 12 days (IQR 5-26 days). The relative risk reductions in CV death/HHF and HHF were similar (p for interaction=0.65 and 0.44) whether treatment was initiated <42 days or ≥42 days after the index CVH. Because event rates were higher in the <42 days group, this subgroup had higher absolute risk reductions (rate of CV death/HHF 11.4% in epl versus 17.0% in the pbo arm in the <42 days group, 10.0% versus 13.6% in the ≥42 days group). In the second analysis, patients randomized to epl had a lower risk for CV death/HHF at 30 days compared to patients receiving pbo (HR=0.51, CI=0.31-0.85, p<0.01). Similarly effects were observed for 30 day HHF (HR=0.44, CI=0.25-0.78, p<0.01). Conclusion: These analyses show that in patients with HFrEF and mild symptoms, epl 1) improves outcome when initiated shortly after a CVH, 2) leads to a significant decrease in CV death/HFH as early as 30 days. These data suggest that initiating eple in patients with HF and mild symptoms soon after hospitalization might reduce the high event rate observed.