Evaluation of eplerenone in the subgroup of EPHESUS patients with baseline left ventricular ejection fraction ≤30%

Abstract

Aims: Because of the prognostic importance of LV dysfunction following an AMI and the increasing use of electrical and/or mechanical interventions in patients with LV systolic dysfunction, this retrospective analysis of EPHESUS patients with LVEF 30% at baseline was conducted to determine the value of eplerenone in this setting. Methods and results: In EPHESUS, 6632 patients with LVEF 40% and clinical heart failure (HF) post-AMI who were receiving standard therapy were randomized to eplerenone 25 mg/day titrated to 50 mg/day or placebo for a mean follow-up of 16 months. Treatment with eplerenone in the subgroup of patients with LVEF 30% (N = 2106) resulted in relative risk reductions of 21% versus placebo in both allcause mortality ( P = 0.012) and cardiovascular (CV) mortality/CV hospitalization ( P = 0.001), and 23% for CV mortality ( P = 0.008). The relative risk of sudden cardiac death (SCD) was reduced 33% ( P = 0.01) and HF mortality/HF hospitalization was reduced 25% ( P = 0.005) with eplerenone compared with placebo. Within 30 days of randomization, eplerenone resulted in relative risk reductions of 43% for all-cause mortality ( P = 0.002), 29% for CV mortality/CV hospitalization ( P = 0.006), and 58% for SCD ( P = 0.008). Conclusions: Treatment with eplerenone plus standard therapy in patients with post-AMI HF and LVEF 30% provided significant incremental benefits in reducing both early and late mortality and morbidity.

Effect of spironolactone on ventricular arrhythmias in patients with left ventricular systolic dysfunction and implantable cardioverter defibrillators

“…6 In a subgroup of patients in the EPHESUS trial with LVEF < 30%, the relative risk reduction for sudden cardiac death and all-cause mortality was significantly incremental with the use of a selective AA (Eplerenone). 7 Systematic reviews of clinical trials studying the efficacy of AA in HF revealed a significant reduction in all-cause mortality and sudden cardiac death. 8,9 Mortality and morbidity was improved in a randomised clinical trial among patients with mild chronic systolic HF (NYHA Class II) and LV dysfunction.…”

ICD Implantation in Patients with Nonischemic Heart Failure

“…These treatments reduce not only total mortality but also specifically the rate of sudden cardiac death. 4,5 We agree with the comment by McMurray in the accompanying editorial that trials involving patients at higher risk should be considered. …”

A systematic review and economic evaluation of the clinical effectiveness and cost-effectiveness of aldosterone antagonists for postmyocardial infarction heart failure

“…A subgroup of patients with severe LSVD in EPHESUS with LVEF < 35% has been investigated. 52 Baseline LVEF was approximately 25% in RALES, 33% in EPHESUS and 38% for the ischaemic group from AREA IN-CHF; the range of LVEF in the ischaemic group from AREA IN-CHF was 16-58%, therefore some patients were recruited who did not have LVSD despite the inclusion criteria.…”

“…Given the small size and poorer quality of the trials by Ruta et al 48 and Tu and Chen, 49 clinical effectiveness can only be reliably assessed using the three main trials: EPHESUS (eplerenone), 27,52 RALES (spironolactone), 31 and AREA IN-CHF (canrenone). 50 The exchangeability between the the drugs and the three trials are discussed in the following sections.…”