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Impact of eplerenone on major cardiovascular outcomes in patients with systolic heart failure according to baseline heart rate

Journal article
Authors K. L. Chin
T. Collier
S. Pocock
B. Pitt
J. J. V. McMurray
D. J. van Veldhuisen
Karl Swedberg
J. Vincent
F. Zannad
D. Liew
Published in Clinical Research in Cardiology
Volume 108
Issue 7
Pages 806-814
ISSN 1861-0684
Publication year 2019
Published at Institute of Medicine
Pages 806-814
Language en
Keywords ClinicalTrials, gov identifier: NCT00232180, Heart rate, Aldosterone antagonists, Aldosterone, Heart, reduced ejection fraction, mild patients hospitalization, atrial-fibrillation, cost-effectiveness, aldosterone, risk, spironolactone, association, ivabradine, survival, Cardiovascular System & Cardiology
Subject categories Other Medical Sciences


BackgroundIncreased resting heart rate is a risk factor for cardiovascular mortality and morbidity. Mineralocorticoid receptor antagonists (MRAs) have been shown to improve cardiac sympathetic nerve activity, reduce heart rate and attenuate left ventricular remodelling. Whether or not the beneficial effects of MRA are affected by heart rate in heart failure patients with reduced ejection fraction (HFREF) is unclear.MethodsWe undertook a secondary analysis of data from the Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure study to assess if clinical outcomes, as well as the efficacy of eplerenone, varied according to heart rate at baseline.ResultsHigh resting heart rate of 80bpm and above predisposed patients to greater risk of all outcomes in the trial, regardless of treatment allocation. The beneficial effects of eplerenone were observed across all categories of heart rate. Eplerenone reduced the risk of primary endpoint, the composite of cardiovascular death and hospitalisation for heart failure, by 30% (aHR 0.70; 95% CI 0.54-0.91) in subjects with heart rate80bpm, and by 48% (aHR 0.52; 95% CI 0.33-0.81) in subjects with heart rate60bpm. Eplerenone also reduced the risks of hospitalisation for heart failure, cardiovascular deaths and all-cause deaths independently of baseline heart rate.ConclusionsBaseline heart rate appears to be an important predictor of major clinical outcome events in patients with HFREF, as has been previously reported. The benefits of eplerenone were preserved across all categories of baseline heart rate, without observed heterogeneity in the responses.

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