Eplerenone in chronic heart failure with depressed systolic function.

Eplerenone is a selective mineralocorticoid receptor antagonist that has been recently included in the treatment of patients with chronic heart failure (CHF) and reduced systolic function. This brief review aims to summarize current evidence on the role of eplerenone in the therapy of patients with CHF. In the EPHESUS trial, 6632 post-myocardial infarction patients with ejection fraction (EF) <40% and clinical HF signs were randomized to eplerenone or placebo added to standard therapy 3 to 14 days after the event. After a 16 month follow-up period, eplerenone given early (<7 days) reduced the primary endpoints of all-cause mortality by 15% and cardiovascular death or cardiovascular hospitalization by 13%. In the subsequent EMPHASIS-HF trial, the efficacy and tolerability of eplerenone were tested in patients with mild CHF (NYHA functional class II) and EF ≤ 30% or between 30 and 35% with QRS duration >130 ms. After a median follow-up of 21 months eplerenone significantly reduced (by 37%) the primary composite outcome of risk of death from CV causes and first hospitalization for HF. Based on the above findings, the addition of eplerenone to standard therapy, at doses to be titrated from 25 to 50mg per day, is currently recommended in CHF patients with functional classes II to IV closely resembling those enrolled in these large clinical trials, with adequate monitoring for side effects (mainly hyperkalemia and renal failure). Whether the same beneficial effects of eplerenone extend to CHF patients with mild symptoms and no additional risk factors are unknown.