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

Abstract

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.

Reappraisal on pharmacological and mechanical treatments of heart failure

“…Eplerenone was well-tolerated in Japanese patients with HFrEF and showed results consistent with those reported in the EMPHASIS-HF [60]. In EPHESUS, eplerenone reduced hospitalizations and mortality in HFrEF/HEpEF [61], regardless of percutaneous coronary intervention [62]. However, no relevant studies support the hypothesis that eplerenone has a significantly beneficial effect on glucose homeostasis in patients with HFrEF and either glucose intolerance or diabetes [63].Finerenone was well tolerated and induced a 30% or greater decrease in NT-proBNP levels in a similar proportion of patients to eplerenone [64], and finerenone was well tolerated in Japanese patients in ARTS-HF Japan [65].…”

Predictors of the Use of Mineralocorticoid Receptor Antagonists in Patients With Left Ventricular Dysfunction Post‐ST‐Segment–Elevation Myocardial Infarction

“…However, there was a mortality benefit across the LVEF range studied in the EPHESUS trial. 7 , 19 This highlights that clinicians caring for patients post‐MI with LV dysfunction should consider therapy even among patients with only “mildly” reduced LVEF.…”

Prognostic impact of additional mineralocorticoid receptor antagonists in octogenarian heart failure patients

“…Although medical management including GDMT and MRA has not been sufficiently studied in patients with HFmrEF, more than 70% of them received RASi and BB, and more than 40% received MRA 20 . There are some studies demonstrating the benefit of these medications in HFmrEF patients 34–37 . Considering the results from these studies and the current medical management practice for patients with HFmrEF, we included this population for analysis in the current study.…”

“…20 There are some studies demonstrating the benefit of these medications in HFmrEF patients. [34][35][36][37] Considering the results from these studies and the current medical management practice for patients with HFmrEF, we included this population for analysis in the current study. However, we need to be careful in adapting this result to patients with HFmrEF.…”