Biomarkers such as galectin-3 which reflect
ongoing remodeling may provide complementary
information regarding the natriuretic peptides used
in the management of chronic HF with regard to risk
stratification for future adverse cardiac events including
death, myocardial infarction, and need for heart
transplantation.[
10] Plasma galectin-3 measurement is
cost-effective, readily available, easily interpretable,
and suitable for low-income individuals similar to
those included in our study.
The physiological importance of spironolactone is
indirect regulation of blood volume and blood pressure
by sodium retention. However, spironolactone also
plays an essential role in the pathogenesis of HF.[17] By antagonizing spironolactone, MRAs can prevent
the pathophysiological effects of sodium retention,
cardiac hypertrophy, and cardiac fibrosis.[12]
Currently, the success of several MRAs has been
already established in HF. First, the Randomized
Aldactone Evaluation Study (RALES) trial determined
the efficacy of co-therapy with spironolactone in
patients with severe HF (LVEF ?35%) compared
to placebo.[18] The primary efficacy end-point was
all-cause mortality and secondary endpoints included
cardiovascular death and hospitalization and change
in the NYHA class. Spironolactone treatment proved
to be successful in reducing the risk for all-cause
mortality (30% risk reduction) and prespecified
secondary outcomes, compared to placebo, regardless
of age. Second, The Eplerenone in Patients with Heart
Failure Due to Systolic Dysfunction Complicating
Acute Myocardial Infarction (EPHESUS) trial
investigators investigated the efficacy of eplerenone
treatment in addition to optimal treatment in a multicenter,
double-blind, randomized trial in patients with
LV dysfunction (LVEF ?40%) after acute myocardial
infarction. Treatment with eplerenone led to a reduction
of overall mortality (by 15%) and to a reduction of
cardiovascular death and hospitalization (by 13%)
compared to placebo. The Effect of Eplerenone versus
Placebo on Cardiovascular Mortality and Heart Failure
Hospitalization in Subjects with NYHA Class II
Chronic Systolic Heart Failure (EMPHASIS-HF)
trial also investigated the effectiveness of eplerenone
in patients with systolic HF (LVEF ?35%) and mild
HF symptoms.[19,20]
In the present study, plasma galectin-3 concentration
in clinical groups were identical at the beginning of
treatment. Upon randomization, in the eplerenone
group, plasma galectin significantly decreased after
four months than in patients receiving spironolactone.
In the patients receiving spironolactone, plasma
galectin-3 level did not significantly change. Although
eplerenone and spironolactone have the same effect
on the treatment of HF,[21,22] they have different
molecular structures, pharmacodynamics, and
pleiotropic effects.[16] Clinical practice guidelines do
not specifically discriminate between these two agents
for the use of an MRA in this setting.[21,22] There
may be slight differences in the MRAs' metabolic
activities. We can detect these differences via new
emerging biochemical markers, such as galectin-3.
In our study, we showed that, there was a significant
difference in reducing galectin-3 levels in favor of the
eplerenone group. Eplerenone treatment differs from
spironolactone in this setting. Although there is no
clear discrimination in the clinical practice guidelines
so far, we can obtain new data with metabolic studies
to clarify the difference of these agents.
The main limitation of our study is its limited
sample size. In addition, we were unable to test
clinical outcomes. Nevertheless, this study provides
evidence regarding the superiority of eplerenone to
spironolactone in reducing galectin-3 levels.
In conclusion, our study findings indicate that
the metabolic effects of eplerenone are different from
those of spironolactone and eplerenone may be superior
to spironolactone in the way of metabolic aspect in
patients with HF. Additional large-scale studies are
still needed to clarify the relationship of eplerenone
treatment and plasma galectin-3 levels in adjusting
HF treatment.
Declaration of conflicting interests
The authors declared no conflicts of interest with respect
to the authorship and/or publication of this article.
Funding
The authors received no financial support for the research
and/or authorship of this article.
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