Eplerenone and Atrial Fibrillation in Mild Systolic Heart Failure: Results From the EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization And SurvIval Study in Heart Failure) Study

Study Questions:

Does eplerenone prevent atrial fibrillation/flutter (AF/Fl) when added to an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin-receptor blocker (ARB)?


Patients (mean age 69 years) with New York Heart Association functional class II heart failure (HF) and an ejection fraction <35% who were being treated with an ACEI or ARB were randomly assigned to treatment with eplerenone (n = 1,364) or a matching placebo (n = 1,373). The study endpoint was new-onset AF/Fl.


Thirty-four percent of patients had AF/Fl at baseline. New-onset AF/Fl occurred during the study period significantly less often in the eplerenone group (2.7%) than in the placebo group (4.5%). Eplerenone significantly reduced the risk of cardiovascular mortality and HF hospitalization by approximately 35% regardless of whether or not AF/Fl was present at baseline.


The authors concluded that eplerenone reduces the risk of new-onset AF/Fl in patients with mild HF by approximately 40%.


Activation of the renin-angiotensin-aldosterone system in HF promotes atrial fibrosis and remodeling, which contribute to the pathogenesis of AF/Fl. ACEIs and ARBs initially were thought to prevent AF/Fl by causing reverse remodeling, but this has not been borne out in large randomized clinical trials. Eplerenone is a mineralocorticoid antagonist (MRA) and has been shown to attenuate structural remodeling in animal models. This may explain why eplerenone reduced the risk of AF/Fl in the present study.

Clinical Topics: Heart Failure and Cardiomyopathies, Acute Heart Failure, Chronic Heart Failure

Keywords: Heart Diseases, Risk, Proto-Oncogene Proteins, Renin-Angiotensin System, New York, Heart Failure, Systolic, Receptors, G-Protein-Coupled

< Back to Listings