Eplerenone in Patients with Systolic Heart Failure and Mild Symptoms: Analysis of Repeat Hospitalizations
Background—Eplerenone is known to reduce time to first hospitalization for heart failure or cardiovascular death in patients with mild heart failure. In chronic diseases such as heart failure, characterised by repeat hospitalizations, analysing all heart failure hospitalizations, not just the first, should give a more complete picture of treatment benefits.
Methods and Results—The Eplerenone in Mild Patients Hospitalization and SurvIval Study in Heart Failure trial (EMPHASIS-HF), compared eplerenone with placebo in 2737 patients with mild heart failure, followed for a median 2.08 years (IQR: 1.08 to 3.10 years). Data were collected on all hospitalizations, with a focus on those due to heart failure. Heart failure hospitalization rates in the eplerenone and placebo groups were 10.70 and 16.99 per 100 patient years respectively. Allowing for skewness in the frequency of hospitalizations by using the Negative Binomial generalized linear model, the rate ratio (eplerenone versus placebo) was 0.53 (95% confidence interval 0.42 to 0.66, P<0.0001). A plot of cumulative hospitalization rates over time revealed that most of the reduced risk on eplerenone occurred in the first year of follow-up. Several baseline variables strongly predicted the risk of hospitalization. More complex statistical methods, adjusting for mortality (as informative censoring), made negligible difference to these findings.
Conclusions—Eplerenone markedly reduces the risk of heart failure hospitalizations in patients with mild heart failure, to a greater extent than is captured by only studying time to first hospitalization. Future clinical trials in heart failure would gain from incorporating repeat hospitalizations into their primary evaluation of treatment effects.
Clinical Trial Registration Information—clinicaltrials.gov; Identifier: NCT00232180.
- Received April 17, 2012.
- Accepted August 28, 2012.
- Copyright © 2012, American Heart Association, Inc. All rights reserved. Unauthorized use prohibited