"Eplerenone in Patients with Systolic Heart Failure and Mild Symptoms".
The New England Journal of Medicine. 2011. 364(1):11-21.
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Contents

1 Clinical Question
2 Bottom Line
3 Major Points
4 Guidelines
5 Design
6 Population
6.1 Inclusion Criteria
6.2 Exclusion Criteria
6.3 Baseline Characteristics
7 Interventions
8 Outcomes
8.1 Primary Outcome
8.2 Secondary Outcomes
9 Safety
10 Funding
11 Further Reading

Clinical Question

In patients with chronic systolic heart failure and mild symptoms, does the addition of eplerenone improve cardiovascular outcomes?

Bottom Line

In patients with chronic systolic heart failure and mild symptoms, the addition of eplerenone reduced the composite outcome of cardiovascular death or hospitalization for heart failure, as well as other critical endpoints including all-cause mortality.

Major Points

Guidelines

Current guidelines recommend the use of a mineralocorticoid-receptor antagonist in patients with systolic heart failure (NYHA functional class II-IV) who also have an LVEF ≤35%, following myocardial infarction with LVEF ≤40%, or in patients with diabetes mellitus after myocardial infarction.

Design

Multicenter, double-blind, parallel-group, randomized, placebo-controlled trial.
N=2737 patients with chronic systolic heart failure and NYHA class II symptoms.

Interventions: Eplerenone (up to 50 mg daily) vs. placebo.

Follow-up period: Median of 21 months.

Population

Inclusion Criteria

- Age ≥55 years.
- NYHA functional class II heart failure.
- Ejection fraction ≤35%.
- Ongoing treatment with ACE inhibitors or ARBs and beta-blockers at recommended or maximal tolerated doses.
- Hospitalization for a cardiovascular reason within 6 months prior to screening, or elevated BNP or NT-proBNP levels.

Exclusion Criteria

- Acute myocardial infarction.
- NYHA class III or IV heart failure.
- Serum potassium level >5.0 mmol per liter.
- Estimated GFR <30 mL/min/1.73 m².
- Need for potassium-sparing diuretic.
- Clinically significant coexisting condition.

Baseline Characteristics

- Well-matched groups.
- All patients receiving standard pharmacologic therapy for systolic heart failure.

Interventions

- Eplerenone starting dose of 25 mg once daily, increased to 50 mg daily if tolerated and based on serum potassium levels.
- Placebo group on matching dummy treatment.

Outcomes

Primary Outcome

- Combined death from cardiovascular causes or first hospitalization for heart failure.

Secondary Outcomes

- Hospitalization for heart failure or death from any cause.
- Death from any cause.
- Death from cardiovascular causes.
- Hospitalization for any reason.
- Hospitalization for heart failure.

Safety

- Hyperkalemia was more frequent in the eplerenone group, requiring careful monitoring and adjustment of the study drug dosage.

Funding

Supported by Pfizer.

Further Reading

For additional information, the following materials are available:
- Supplementary Appendix, available at NEJM.org.
- Reprint requests and other correspondence can be addressed to Dr. Faiez Zannad.