Eplerenone Reduces Atrial Fibrillation Incidence in Heart Failure Patients

Atrial fibrillation (AF) is commonly seen with systolic heart failure and may be associated with worse prognosis and clinical deterioration. For this reason, there is widespread interest in better characterizing the development of AF and working to develop novel therapies for decreasing its incidence. Recently, the aldosterone antagonists have entered the armamentarium of heart failure therapies and have been shown in clinical trials to significantly decrease adverse cardiovascular outcomes.

The EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure) study was a large randomized controlled trial of 2737 patients with New York Heart Association (NYHA) Class II symptoms and a left ventricular ejection fraction of ≤35%.¹ This trial was prematurely terminated after a median follow-up of 21 months because of a significant benefit with eplerenone in the primary outcome measure of death from cardiovascular causes or hospitalization for heart failure (HR = 0.63; 95% CI, 0.54-0.74).
 
Swedberg et al² have subsequently published a fascinating sub-study from this trial in The Journal of the American College of Cardiology showing that aldosterone antagonism significantly reduced new-onset AF or flutter (2.7% vs 4.5%) in this population. Interestingly, there was no significant difference in the rate of the primary composite end point stated above in those with and without AF/flutter at baseline and no difference in benefit derived from eplerenone based on the presence of AF/flutter at baseline.
 
The mechanism underlying this reduction in incidence remains uncertain, but it may be a result of decreased atrial fibrosis and remodeling with eplerenone or diminished electrical instability as a result of reduced hypokalemia. Additional research will shed light on how it works; right now, however, for primary care physicians who have patients with NYHA Class II systolic heart failure and are at risk for developing AF or flutter, therapy with an aldosterone antagonist should be considered.

References:
1. Zannad F, McMurray JJ, Krum H, et al. Eplerenone in patients with systolic heart failure and mild symptoms. N Engl J Med. 2011;364:11-21.
2. Swedberg K, Zannad F, McMurray JJ, et al. 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. J Am Coll Cardiol. 2012;59:1598-1603. (Abstract)