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.

Abstract:

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', > or =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 (> or =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 (> or =7days).

journal_name

Eur J Heart Fail

authors

Adamopoulos C,Ahmed A,Fay R,Angioi M,Filippatos G,Vincent J,Pitt B,Zannad F,EPHESUS Investigators.

doi

10.1093/eurjhf/hfp136

subject

Has Abstract

pub_date

2009-11-01 00:00:00

pages

1099-105

issue

11

eissn

1388-9842

issn

1879-0844

pii

hfp136

journal_volume

11

pub_type

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