Elsevier

American Heart Journal

Volume 160, Issue 5, November 2010, Pages 915-921
American Heart Journal

Clinical Investigation
Congestive Heart Failure
Effect of eplerenone versus spironolactone on cortisol and hemoglobin A1c levels in patients with chronic heart failure

https://doi.org/10.1016/j.ahj.2010.04.024Get rights and content

Background

It has been reported that mineralocorticoid receptor antagonist improves the prognosis of chronic heart failure (CHF). Recently, hemoglobin A1c (HbA1c) levels have been reported to be an independent risk factor for mortality in CHF, suggesting the important role of insulin resistance in CHF. We compared the metabolic effect of a selective mineralocorticoid receptor blocker eplerenone with spironolactone in CHF patients.

Methods

One hundred seven stable outpatients with mild CHF, who were already receiving standard therapy for CHF, were randomized (1:2) to spironolactone (25 mg/d) or eplerenone (50 mg/d). Plasma levels of B-type natriuretic peptide, adiponectin, HbA1c and cortisol were measured before and after 4 months treatment with spironolactone or eplerenone.

Results

There were no differences in baseline characteristics including hemodynamic parameters and plasma levels of biomarkers between 2 groups. In both groups, plasma B-type natriuretic peptide levels were significantly decreased and plasma aldosterone levels were significantly increased after 4 months. In patients receiving spironolactone (n = 34), plasma adiponectin levels were significantly decreased (12.6 ± 1.4-11.2 ± 1.3 μg/mL, P < .0001) and HbA1c and cortisol levels were significantly increased (5.61 ± 0.1-5.8 ± 0.1%, P < .0001, 11.3 ± 0.8-14.7 ± 1.3 μg/dL, P = .003, respectively). In patients receiving spironolactone, there was a significant positive correlation between the change in cortisol and the change in HbA1c (r = 0.489, P = .003). In contrast, in patients receiving eplerenone (n = 73), plasma levels of adiponectin, HbA1c and cortisol did not change.

Conclusion

These findings indicated that the metabolic effect of eplerenone differed from that of spironolactone and that eplerenone had a superior metabolic effect especially on HbA1c in CHF patients.

Section snippets

Patients

The study subjects were 107 stable outpatients with mild CHF (NYHA class I or II) who had already been receiving standard therapy for >6 months. Patients with CHF were defined as patients who had previously been admitted to hospital for management of CHF due to systolic heart failure, which was defined as left ventricular ejection fraction (LVEF) <45% by 2-dimensional echocardiography or ventriculography using contrast medium or radioisotope, or had already been receiving treatment for CHF

Baseline clinical characteristics

There was no difference in baseline hemodynamic parameters including LVEF between the 2 groups (Table I). At entry into the study, most patients were receiving ACEI or ARB and β-blockers. There were no significant differences in the proportion of CHF patients with diabetes mellitus (DM) (P = .35) or the distribution of anti-diabetic therapies including diet therapy between the 2 groups (P = .76). Further, hydrophilic statin was mainly used for lipid lowering therapy and there was no difference

Discussion

In this study, we demonstrated for the first time that treatment with spironolactone for 4 months increased plasma HbA1c levels and serum cortisol levels in patients with CHF, while treatment with eplerenone did not. Furthermore, Δincrease in plasma HbA1c levels was positively correlated with Δincrease in cortisol levels after treatment with spironolactone. These findings suggest that eplerenone may be more useful than spironolactone for the treatment of CHF patients with DM, who easily

Conclusions

These findings indicated that a selective MR blocker eplerenone was superior to spironolactone due to differences in metabolic effects especially those on HbA1c in CHF patients. Compared with spironolactone, eplerenone may be more useful for treatment of CHF patients from the perspective of insulin resistance and cortisol levels, which were related to poor prognosis.

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