EPHESUS trial (treatment of heart failure)

Last reviewed 09/2022

The EPHESUS trial (1) recruited 6632 patients with heart failure or left ventricular dysfunction in the context of acute myocardial infarction. In addition to conventional treatment patients were randomised to the selective aldosterone antagonist eplerenone or placebo.

The study found a clear 15% reduction in all-cause mortality. Eplerenone (in addition to standard therapy) significantly reduced mortality in patients with LVSD and heart failure equating to a NNT of 44 for all-cause mortality and 50 for mortality associated with cardiovascular disease.

This trial shows that aldosterone antagonists are useful even in asymptomatic left ventricular dysfunction as well as more severe heart failure (2).

Eplerenone use is associated with the an increased risk of hyperkalaemia compared with placebo (3.4% vs 2%, p < 0.001). The incidence of gynaecomastia as an adverse effect is low and occurred with equal incidence in the eplerenone and placebo treated groups (3).


  1. Pitt B, Remme W, Zannad F, Neaton J, Martinez F, Roniker B, Bittman R, Hurley S, Kleiman J, Gatlin M; Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study Investigators. (2003). Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med. 348(22):2271.
  2. Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, Palensky J, Wittes J. (1999). The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med. 341(10):709-17.
  3. Midland Therapeutic Review and Advisory Committee (March 2005). Eplerenone.