• Randomized, double-blind, placebo-controlled trial
• 2737 patients with NYHA class II symptoms, age ≥55 years, LV ejection fraction (EF) ≤30% (if LVEF >30-35%, a QRS duration of >130 msec)
• Randomized within 6 months after hospitalization for a cardiovascular cause or if not applicable, could be randomized if BNP level ≥250 pg/mL or if N-terminal pro-BNP ≥500 pg/mL (men) and ≥750 pg/mL (women)
• Receiving an ACE inhibitor, angiotensin-receptor blocker or both and a beta-blocker (unless contraindicated) at the recommended dose or maximal tolerated dose

• Acute MI, NYHA class III or IV HF
• Potassium level >5 mmol/L, eGFR <30 mL/min/1.73 m²
• Need for potassium sparing diuretic
• Other clinically significant, coexisting condition

• Eplerenone 25 mg PO daily, increased to 50 mg PO daily after 4 weeks vs. placebo
• if eGFR 30-49 mL/min/1.73m2 and potassium <5 mmol/L): Eplerenone 25 mg PO on alternate days, increased to 25 mg PO daily after 4 weeks vs placebo
• Potassium levels were checked every 4 months and dose decreased if potassium 5.5-5.9 mmol/L and drug stopped if potassium ≥ 6 mmol/L.
• Potassium rechecked within 72 hours after dose reduction or cessation of drug and resumption of drug allowed only if potassium level <5 mmol/L.

Primary Endpoints

Death from cardiovascular causes or hospitalization for heart failure: 18.3% (epleronone) vs 25.9% (placebo); adjusted hazard ratio 0.63, p<0.001.

Secondary Endpoints (see study for complete list)

Eplere- none n=1364	Placebo n=1373	Hazard Ratio	p
All cause mortality or hospitalization for heart failure
19.8%	27.4%	0.65 (0.55-0.76)	<0.001
All cause mortality
12.5%	15.5%	0.76 (0.62-0.93)	0.008
CV death
10.8%	13.5%	0.76 (0.61-0.94)	0.01
Hospitalizations for heart failure
12%	18.4%	0.58 (0.47-0.70)	<0.001

• There were no deaths attributed to hospitalization for worsening renal function or hyperkalemia.
• Potassium level >5.5 mmol/L occurred in 11.8% of patients in the eplerenone group vs. 7.2% of patients in the placebo group (p<0.001)