PRACTICE CHANGER
Prescribe a mineralocorticoid-receptor antagonist for patients with New York Heart Association (NYHA) Class II systolic heart failure and an ejection fraction (EF) ≤30%. Eplerenone has been found to decrease hospitalizations for heart failure and cardiovascular and all-cause mortality.1
STRENGTH OF RECOMMENDATION
A: Based on one high-quality randomized controlled trial (RCT).
Zannad F, McMurray JJ, Krum H, et al; EMPHASIS-HF Study Group. Eplerenone in patients with systolic heart failure and mild symptoms. N Engl J Med. 2011;364:11-21.
ILLUSTRATIVE CASE
A 56-year-old man with a history of systolic heart failure and an EF of 30% returns to your clinic for routine follow-up. He reports that he gets mildly short of breath while mowing the lawn, but his condition is stable. He’s already taking an angiotensin-converting enzyme inhibitor (ACEI) and a beta-blocker, and his potassium level is 4.8 mmol/L. Should he also be taking eplerenone?
Heart failure has reached epidemic proportions in the United States.2-4 Each year, heart failure accounts for more than 1 million hospitalizations,3,5 and millions more are living with the disease.2 ACEIs and beta-blockers are known to decrease hospitalization and mortality for these patients. Recent evidence suggests that mineralocorticoid-receptor antagonists have additional benefits.2,4,6
Benefits for Class III and IV heart failure are well established
The Randomized Aldactone Evaluation Study (RALES) showed that spironolactone decreased all-cause mortality and hospitalization for cardiovascular causes in patients with Class III and IV heart failure.7 In the Ephesus study, the addition of eplerenone to optimal therapy reduced morbidity and mortality in patients with a myocardial infarction (MI) complicated by systolic heart failure.8 These studies led to the current guidelines, which recommend using a mineralocorticoid-receptor antagonist for patients with NYHA Class III and IV heart failure, as well as patients with acute MI and either left ventricular dysfunction or heart failure.2,4,6 Until recently, however, there was no reason to think about using this class of medications for patients with less severe disease.
STUDY SUMMARY: Eplerenone improves outcomes for patients with mild symptoms
The Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF)1 was a randomized, double-blinded trial designed to evaluate the effect of eplerenone on patients with less severe disease. Eligible patients were older than 55 years, with Class II heart failure and an EF ≤30% (or >30%-35% with a QRS interval >130 ms). Their existing drug regimen had to include an ACEI, angiotensin receptor blocker, or both, as well as a beta-blocker. Patients with a potassium level >5.0 mmol/L, acute MI, or a low glomerular filtration rate (GFR <30 mL/min) were excluded.
Randomization occurred within 6 months of hospitalization for a cardiovascular disorder; study participants without a recent hospitalization were included if they had either a plasma level of B-type natriuretic peptide (BNP) >250 pg/mL or a pro-BNP >500 pg/mL for men or >750 pg/mL for women. A total of 2737 patients were randomized to receive either eplerenone 25 mg/d (the daily dosage was increased to 50 mg after 4 weeks if the potassium level remained <5 mmol/L) or placebo. Patients with an estimated GFR of 30 to 49 mL/min were started on 25 mg eplerenone every other day; if that dose was tolerated, it was increased to 25 mg/d after 4 weeks.
The primary outcome was a composite of death from cardiovascular causes or a first hospitalization for heart failure. Secondary outcomes included any hospitalization for heart failure, all-cause mortality, and cardiovascular death.
Patients were evaluated every 4 months. The dose of the eplerenone was decreased if the potassium level was 5.5 to 5.9 mmol/L, and stopped altogether if potassium was >6 mmol/L. Potassium levels were measured within 72 hours of a dosage change, and the drug restarted if potassium levels returned to <5.0 mmol/L.