Eplerenone in patients with myocardial infarction and mid-range ejection fraction: An analysis from the EPHESUS trial

Background Trials using mineralocorticoid receptor antagonists (MRAs) in myocardial infraction (MI) without heart failure (HF) or systolic impairment have been underpowered to assess morbidity-mortality benefit. In EPHESUS 6632 patients were included, of whom 11% had an ejection fraction (EF) of 40% and HF or diabetes. We aim to assess the potential benefit of MRAs in MI with EF of 40%. Methods Cox models with interaction term for EF. The primary outcome was a composite of cardiovascular death or hospitalization for cardiovascular reasons. Hypothesis Patients with an EF of 40% benefit similarly from MRA therapy to those with an EF <40%. Results In EPHESUS, 753 patients had an EF = 40% and 5864 an EF < 40%. Patients with an EF = 40% were younger (63 vs 64 years), had lower heart rate (73 vs 75 bpm), less atrial fibrillation (10% vs 14%), previous MI (21% vs 28%), HF hospitalization (5% vs 8%), and had more often reperfusion therapy and/or revascularization (55% vs 44%). The mean EF was 40.0 +/- 0.3% in those with EF = 40% vs 32.2 +/- 5.9% in those with EF < 40%. The primary outcome occurred in 13.3% (10 events per 100 py) of the patients with EF = 40% vs 22.9% (19 events per 100 py) in those with EF < 40%; adjusted HR for EF = 40% vs <40% = 0.65 (0.53-0.81). Eplerenone reduced the event-rate homogenously regardless of EF (interaction(p) EF = 40% vs EF < 40% = 0.21). Similar findings were observed for cardiovascular and all-cause death. Conclusion Eplerenone reduces hospitalizations and mortality in patients with MI and EF = 40% similarly to patients with EF < 40%. These findings suggest that MI patients with EF in the mid-range zone may also benefit from MRA therapy which might help clinicians in their treatment decisions.