Effect of eplerenone versus spironolactone on cortisol and hemoglobin A1c levels in patients with chronic heart failure

Background It has been reported that mineralocorticoid receptor antagonist improves the prognosis of chronic heart failure (CHF). Recently, hemoglobin A1c (HbA(1c)) 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 mu g/mL, P<.0001) and HbA(1c) and cortisol levels were significantly increased (5.61 +/- 0.1-5.8 +/- 0.1%, P<.0001, 11.3 +/- 0.8-14.7 +/- 1.3 mu g/dL, P=.003, respectively). In patients receiving spironolactone, there was a significant positive correlation between the change in cortisol and the change in HbA(1c) (r=0.489, P=.003). In contrast, in patients receiving eplerenone (n=73), plasma levels of adiponectin, HbA(1c) 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 HbA(1c) in CHF patients. (Am Heart J 2010;160:915-21.)