Eplerenone mechanism in HF independent of diuretic effect
MedWire News: Analysis of the EPHESUS trial has shown that the benefits of eplerenone on long-term survival and outcomes in heart failure (HF) patients appear to go beyond effects related to its diuretic properties.
In the setting of HF post-myocardial infarction, these data provide important pathophysiological insights into eplerenone's beneficial effects that may involve, but are independent from, an early detectable significant diuretic and potassium-sparing effect, report Patrick Rossignol (Nancy-Université, France) and co-authors.
As reported previously by MedWire News, EPHESUS (Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study) randomly allocated 6632 patients with systolic HF or left ventricular dysfunction with diabetes within 2 weeks of experiencing acute MI, to receive treatment with eplerenone 25 mg daily (titrated to 50 mg daily), or placebo on top of standard therapy, including loop diuretics.
Over a mean follow-up period of 16 months, the eplerenone group showed a 15% reduction in mortality (p=0.008) and a 13% reduction in cardiovascular mortality or hospitalization (p=0.002), compared with the placebo group.
In the current analysis, Rossignol et al studied the outcomes of the 6080 EPHESUS patients who survived to 1-month follow-up.
Multivariate analysis revealed that diuresis, which was indirectly calculated using estimated plasma volume reduction, was independently associated with significant 11-19% reductions in the risk for all-cause death or hospitalization, cardiovascular death or hospitalization, and hospitalization for HF.
Potassium-sparing, defined as a serum potassium increase greater than the median change in the placebo group (0.11 mmol/L) was also independently associated with a 12-34% reduction in the risk for these outcomes.
Of note, there was no statistically significant interaction between the observed beneficial effects of eplerenone (9-17% reductions in risk) on cardiovascular outcomes and potassium-sparing or diuretic effects, write the authors.
"Thus, although our results suggest that a diuretic-like effect and a potassium-sparing effect of eplerenone can be detected in EPHESUS, the benefit of eplerenone on cardiovascular outcomes cannot be solely explained by these effects, suggesting additional protective cardiovascular pleiotropic effects of eplerenone," they conclude.
The findings are reported in the Journal of the American College of Cardiology.
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By Piriya Mahendra