Inhibition of the mineralocorticoid receptors (= aldosterone receptors) in the kidneys.

• Spironolactone: non-selective, also inhibits androgen receptors (causing gynecomastia in men) and progesterone receptors (causing menometrorrhagia in women)
• Eplerenone: highly selective inhibition of the mineralocorticoid receptors (so that no gynecomastia or menses disorders occur).

• Reduction of sodium and water reabsorption in the kidneys: increased sodium excretion and diuresis.
• Reduction of potassium excretion ('potassium-sparing' diuretic): prevention of hypokalemia during therapy with other diuretics.
• Reduction of sympathetic activity.
• Reduction of hypertrophy of myocytes and fibrosis in the myocardium.

Trials: RALES, EMPHASIS-HF, EPHESUS

• Reduction of all-cause and cardiovascular mortality
• Reduction of hospitalizations for heart failure
• Reduction of symptoms and better quality of life
• Reduction of sudden death

Always consider heart failure with LVEF ≤ 40% and strongly consider if LVEF ≤ 50%, unless contraindicated or intolerance.

• Start at 12.5 or 25 mg per day - increase to 25 mg per day, possibly to 50 mg per day.
• Always check renal function and potassium 2 to 4 weeks after initiation or after a dose increase.
• If potassium > 6 mmol/l:
  • Rule out pseudohyperkalemia.
  • In case of symptoms or possible real hyperkalemia: stop MRA and consult the treating cardiologist and/or nephrologist.
  • Read: hyperkalemia.
• Dose adjustments:

• Hyperkalemia, unless corrected with potassium binder and GFR > 20-30 ml/min.
• eGFR <20 ml/min.

• Increased risk of renal insufficiency and hyperkalemia . See above.
• Spironolactone can cause bilateral, painful gynecomastia . In that case, a switch to Eplerenone can be made in consultation with the treating cardiologist, if the reimbursement criteria are met.
  
  Reimbursement Criteria for Eplerenone in Belgium:
  Eplerenone is only reimbursed in men with previously disabling gynecomastia due to spironolactone and also:

• • HFrEF with LVEF ≤ 40% after recent myocardial infarction.
  • HFrEF with LVEF ≤ 30%.

• Hypotension
• Renal insufficiency
• Hyperkalemia

With spironolactone (NOT with eplerenone):

• Sexual dysfunction: impotence (in men), menometrorrhagia (in women)
• Gynecomastia: bilateral, sometimes painful (in men)