Eplerenone after AMI complicated by heart failure: The earlier, the better

Initiating eplerenone early to patients after acute myocardial infarction (AMI) with associated clinical heart failure and a low ejection fraction results in impressive and significant reductions in mortality and adverse cardiovascular (CV) endpoints. This is according to a new analysis of EPHESUS (Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study), presented by Faiez Zannad, MD, PhD, at the American College of Cardiology's 56th annual scientific session.

In EPHESUS, the main results of which were published in the New England Journal of Medicine (2003; 348:1309-21), 6,632 patients with AMI complicated by left ventricular dysfunction (ejection fraction of <40%) and heart failure were randomized to the aldosterone inhibitor eplerenone (25 mg/d initially, titrated to a maximum of 50 mg/d) or placebo, in addition to optimal medical therapy, starting 3 to 14 days after AMI.

During a mean follow-up of 16 months, eplerenone was associated with a 15% reduction in death (p = 0.008), a 17% reduction in death attributed to cardiovascular causes (p = 0.005), a 13% reduction in death from cardiovascular causes or hospitalization for cardiovascular events (p = 0.002), and a 21% reduction in the rate of sudden death from cardiac causes (p = 0.03).In the current analysis, Dr. Zannad compared 1) early initiation of eplerenone (3 to 7 days after AMI), with placebo on outcomes, and 2) late initiation of eplerenone (8 to 14 days after AMI) with placebo on the same outcomes.

Compared with placebo, starting eplerenone early resulted in a 23% reduction in all-cause mortality (p = 0.003), a 15% reduction in cardiovascular death/hospitalization (p = 0.01), and a 37% reduction in sudden cardiac death (p = 0.002).

In contrast, starting eplerenone from 8 to 14 days after AMI resulted in no significant reductions in these endpoints, compared with placebo.

There was a higher rate of mild hyperkalemia with early initiation of eplerenone, but serious hyperkalemia was rare, occurring in <1% of patients in whom eplerenone was started early, said Dr. Zannad, from Hôpital Jeanne d'Arc, Toul, France.

Early initiation of eplerenone may attenuate ventricular remodeling, extracellular matrix remodeling, and early electrical remodeling, he said.

The significantly improved outcomes with early initiation of eplerenone might persuade for its introduction before discharge in patients who leave the hospital less than 7 days after admission, said Dr. Zannad. A trial of eplerenone started even earlier (<3 days after AMI) may be warranted.