Aldosterone blockade and left ventricular dysfunction: a systematic review of randomized clinical trials

Context Aldosterone blockade has been used to treat acute myocardial infarction (MI) and chronic heart failure. Objective The aim of this study is to summarize the evidence on the efficacy of spironolactone (SP), eplerenone (EP), or canrenoate (CAN) in patients with left ventricular dysfunction. Dat...

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Bibliographic Details
Published in:European heart journal 2009-02, Vol.30 (4), p.469-477
Main Authors: Ezekowitz, Justin A., McAlister, Finlay A.
Format: Article
Language:English
Subjects:
Aged
Biological and medical sciences
Cardiology. Vascular system
Cause of Death
Female
Heart
Heart failure
Heart Failure - drug therapy
Heart Failure - mortality
Heart Failure - physiopathology
Heart failure, cardiogenic pulmonary edema, cardiac enlargement
Hospitalization
Humans
Male
Medical sciences
Meta-analysis
Middle Aged
Mineralocorticoid Receptor Antagonists - adverse effects
Mineralocorticoid Receptor Antagonists - therapeutic use
Randomized Controlled Trials as Topic
Spironolactone
Spironolactone - therapeutic use
Stroke Volume - drug effects
Systematic review
Treatment Outcome
Ventricular Dysfunction, Left - drug therapy
Ventricular Dysfunction, Left - mortality
Ventricular Dysfunction, Left - physiopathology
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Summary:Context Aldosterone blockade has been used to treat acute myocardial infarction (MI) and chronic heart failure. Objective The aim of this study is to summarize the evidence on the efficacy of spironolactone (SP), eplerenone (EP), or canrenoate (CAN) in patients with left ventricular dysfunction. Data sources A search of multiple electronic databases until June 2008 was supplemented by hand searches of reference lists of included studies and review articles, meeting abstracts, FDA reports, and contact with study authors and drug manufacturers. Study selection and data extraction Studies were eligible for inclusion if they included patients with left ventricular systolic or diastolic dysfunction, treatment with SP, EP, or CAN vs. control, and reported clinical outcomes. Nineteen randomized controlled trials (four in acute MI and 15 in heart failure, n = 10 807 patients) were included—14 of SP, three of EP, and three of CAN. Analysis was performed using relative risks (RRs) with 95% confidence intervals (CIs) and a random effects model with statistical heterogeneity assessed by I2. Data synthesis Aldosterone blockade reduced all-cause mortality by 20% (RR 0.80, 95% CI 0.74–0.87). All-cause mortality was reduced in both heart failure (RR = 0.75, 95% CI 0.67–0.84) and post-MI (RR 0.85, 95% CI 0.76–0.95) patients. Only nine trials reported hospitalizations, and the RR reduction was 23% (RR 0.77, 95% CI 0.68–0.87), although 98% of the outcomes came from two trials. Ejection fraction (EF) improved in the seven heart failure trials, which assessed this outcome (weighted mean difference 3.1%, 95% CI 1.6–4.5). Conclusion We demonstrated a 20% reduction in all-cause mortality with the use of aldosterone blockade in a clinically heterogeneous group of clinical trial participants with heart failure and post-MI. In addition, we found a 3.1% improvement in EF. Further study in those with less severe symptoms or preserved systolic function is warranted.
ISSN:0195-668X
1522-9645
DOI:10.1093/eurheartj/ehn543