1. Home>
2. Specialties>
3. Cardiology>
4. Summary and Comment

Eplerenone Effective After MI in Patients with LVSD and Heart Failure

But should eplerenone have preferential status as first therapy?

In the RALES randomized trial, the aldosterone antagonist spironolactone improved outcomes in patients with severe heart failure (HF) and left-ventricular systolic dysfunction (LVSD; N Engl J Med 1999; 341:709). Now, in an industry-sponsored, randomized, placebo-controlled trial, researchers have assessed whether another aldosterone antagonist, eplerenone, improves outcomes 3 to 14 days after MI in patients with LV ejection fractions 40% and HF or diabetes. Subjects were 6632 patients from 674 centers in 37 countries.

Patients with creatinine concentrations >2.5 mg/dL or potassium concentrations >5.0 mmol/L were excluded. At baseline, 88% of patients were receiving aspirin, 87% ACE inhibitors, 75% beta-blockers, and 60% diuretics. Mean follow-up was 16 months.

Compared with placebo recipients, eplerenone recipients had significantly lower follow-up rates of the 2 primary endpoints: all-cause mortality (14.4% vs. 16.7%) and cardiovascular death or first cardiovascular hospitalization (26.7% vs. 30.0%). Eplerenone recipients also had significantly lower rates of cardiovascular death alone (12.3% vs. 14.6%) and sudden cardiac death (4.9% vs. 6.1%). These eplerenone-placebo differences were consistent across many subgroups.

By 1 year, eplerenone recipients had slightly, but significantly, higher rates of worsening renal function (creatinine-concentration increase, 0.06 mg/dL vs. 0.02 mg/dL) and of serious hyperkalemia (5.5% vs. 3.9%) than placebo recipients did.

Comment: This study documents a clinically meaningful post-MI benefit of eplerenone for patients with LVSD and heart failure or diabetes. An editorialist notes that because there is no evidence that eplerenone is more effective than spironolactone in these patients, eplerenone should not have preferential status as first therapy. Furthermore, rates of hyperkalemia are considered to be similar with eplerenone and spironolactone. Eplerenone appears to be superior to spironolactone in avoiding adverse effects such as gynecomastia and impotence. Note that eplerenone is FDA-approved for hypertension, but not yet for post-MI heart failure.

— Harlan M. Krumholz, MD, SM

Published in Journal Watch Cardiology May 2, 2003

Citation(s):

Pitt B et al. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 2003 Apr 3; 348:1309-21.

• Original article (Subscription may be required)
• Medline abstract (Free)

Jessup M. Aldosterone blockade and heart failure. N Engl J Med 2003 Apr 3; 348:1380-2.

• Original article (Subscription may be required)
• Medline abstract (Free)