EMPHASIS-HF Trial - Aldosterone antagonists for NYHA class II heart failure

EMPHASIS HF

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Name: EMPHASIS-HF

Specialty: cardiology, CHF 

Problem: CCF (NYHA II & EF < 35%*)

Population: 2737 patients

Inclusion criteria:
Age > 55 years
NYHA functional class II symptoms
Ejection fraction of no more than 30% (or, if >30 to 35%, a QRS duration of >130 msec)
Treatment with an angiotensin-converting–enzyme (ACE) inhibitor, an angiotensin-receptor blocker (ARB), or both and a beta-blocker (unless contraindicated) at the recommended dose or maximal tolerated dose.
Exclusion criteria:
Acute myocardial infarction
NYHA class III or IV heart failure
Serum potassium > 5.0 mmol per liter
eGFR < 30 ml per minute per 1.73 m2
Need for a potassium-sparing diuretic
Any other clinically significant, coexisting condition.
Intervention: Eplerenone

Control: Placebo

Follow-up: Median 21 months

Primary endpoint:
Composite of death from cardiovascular causes or a first hospitalization for heart failure
Secondary endpoint(s):
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 (among others)
Details:
* = Ejection fraction of no more than 30% (or, if >30 to 35%, a QRS duration of >130 msec)
Patients were randomized to two placebo or eplerenone 25 mg once daily. This dosage increased to 50 mg once daily after 4 weeks or 25 mg on alternate days increased to 25 mg daily. Serum potassium levels were used to guide dose increases and decreases.

Results:
 Eplerenone vs. placebo
-37% reduction in death from CV causes or hospitalisation for HF
--Benefits across all prespecified subgroups -Significant reduction in death from any cause
-Trend towards fewer adverse events in eplerenone group
--Significantly increased risk of hyperkalaemia

How the article changed CHF guidelines: Read below.

In early 2012 HFSA issued new guidelines recommending use of aldosterone antagonists in NYHA class II HF. 

But study was conducted using Pfizer's brand-child drug - Eplerenone.

CAVEATS:

Composite primary outcome – confusing to apply clinically

Pharma funded (Pfizer, maker of eplerenone)

–Eplerenone: $113/month

–Spironolactone: $14/month

NNH for hyperkalemia lower than NNT for reducing death.

However no deaths from hyperkalemia, no difference in hyperK hospitalization rates

Papers

Eplerenone in patients with systolic heart failure and mild symptoms.

 PUBMED LINK TO THE ARTICLE.

NEJM LINK TO THE ARTICLE