#104 Aldosterone antagonists in Heart Failure with Reduced Ejection Fraction (HFrEF) – No longer an afterthought.

CLINICAL QUESTION

QUESTION CLINIQUE

What is the role of aldosterone antagonists in patients with chronic HFrEF?

BOTTOM LINE

RÉSULTAT FINAL

Aldosterone antagonists reduce mortality and hospitalizations in patients with HFrEF (Class II–IV). The benefit appears similar to β-blockers or ACE inhibitors. Close monitoring is required for those at risk of hyperkalemia.

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EVIDENCE

DONNÉES PROBANTES

Two randomized controlled trials:

RALES:¹ 1,663 patients with NYHA class 3-4 heart failure with HFrEF on ACE inhibitors and diuretics. Given spironolactone or placebo. At 24 months:
- Statistically significant reduction in:
  - Mortality: Spironolactone 35%, placebo 46%, Number Needed to Treat (NNT)=10.
  - Cardiovascular hospitalization: 32% vs. 40%, NNT=12.
- Adverse events:
  - Gynecomastia/breast pain in men: Spironolactone 10%, placebo 1%, Number Needed to Harm (NNH)=11.
  - Serious hyperkalemia (potassium ≥6 mmol/L): Not statistically different.
EMPHASIS-HF:² 2,737 patients with NYHA class II HFrEF with majority on ACE inhibitors, and β-blockers. Given eplerenone or placebo. At 21 months:
- Statistically significant reduction in:
  - Mortality: eplerenone 13%, placebo 16%, NNT=34.
  - Cardiovascular hospitalization: 22% vs. 29%, NNT=15.
- Adverse events:
  - Hyperkalemia (>5.5 mmol/L) increased with eplerenone 12%, placebo 7%, NNH=22.
  - No difference in gynecomastia or renal failure.

Two meta-analyses found similar results.^3,4

CONTEXT
CONTEXTE

Aldosterone antagonists compare favourably to other agents used in HFrEF whose relative risk reductions for mortality are:
- Aldosterone antagonists^1,2 ~25%.
- β-blockers⁵ ~29%.
- ACE inhibitors^6,7 ~23%.
Aldosterone antagonists are prescribed at less than half the rate of β-blockers and ACE inhibitors, and represent the greatest potential for increased HFrEF survival.⁸
Titration to target doses of ACE inhibitors and β-blockers before adding aldosterone antagonists has been advocated,⁹ however the usage/doses of these medications were quite different in RALES and EMPHASIS-HF, yet they had similar outcomes.
There is no head-to-head trial of spironolactone vs. eplerenone. Spironolactone ($12/month) could be used first and, if gynecomastia/breast pain develop, switch to eplereonone ($100/month).