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Timing of eplerenone initiation and outcomes in patients with heart failure after acute myocardial infarction complicated by left ventricular systolic dysfunction: insights from the EPHESUS trial †
Author(s) -
Adamopoulos Chris,
Ahmed Ali,
Fay Renaud,
Angioi Michael,
Filippatos Gerasimos,
Vincent John,
Pitt Bertram,
Zannad Faiez
Publication year - 2009
Publication title -
european journal of heart failure
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.149
H-Index - 133
eISSN - 1879-0844
pISSN - 1388-9842
DOI - 10.1093/eurjhf/hfp136
Subject(s) - eplerenone , medicine , cardiology , myocardial infarction , heart failure , placebo , spironolactone , randomization , proportional hazards model , randomized controlled trial , alternative medicine , pathology
Aims To test the hypothesis that an earlier post‐acute myocardial infarction (AMI) eplerenone initiation in patients with left ventricular systolic dysfunction (LVSD) and heart failure (HF) is associated with better long‐term outcomes. Methods and results The 6632 patients of the EPHESUS study were randomized from day 3 to 14 after the index AMI (median = 7 days), of these 3319 were assigned to eplerenone. We analysed the differential effects of time‐to‐eplerenone initiation vs. placebo, based on the median time to initiation of treatment (<7 days—‘earlier’, ≥7days—‘later’). Effects on outcomes were evaluated over a mean 16‐month follow‐up, using Cox proportional hazards regression analysis. The earlier eplerenone initiation (<7 days) reduced the risk of all‐cause mortality by 31% ( P = 0.001) when compared with the ‘earlier’ placebo’ and also reduced the risks of cardiovascular (CV) hospitalization/CV mortality by 24% ( P < 0.0001) and sudden cardiac death (SCD) by 34% ( P < 0.0001). In contrast, later eplerenone initiation (≥7 days) had no significant effect on outcomes. Interactions between time‐to‐randomization and treatment were significant. These associations remained substantially unchanged after risk adjustment in multivariable models. Conclusion An earlier eplerenone administration (3–7days) post‐AMI improved outcomes in patients with LVSD and HF. This benefit was not observed when eplerenone was initiated later (≥7days).