Aldosterone Antagonists

January 9, 2024

For complete individual drug prescribing information (PI) and updates, please refer to the drug manufacturer or FDA websites.

Initiation

Select an initial dose of aldosterone antagonist. It is not necessary to achieve target or maximally tolerated doses of other drugs before adding aldosterone antagonists (EC). Lack of treatment with an aldosterone antagonist should not delay initiating or switching a patient to an ARNI.

  • Spironolactone – Suggested initial dose: 12.5-25 mg daily
  • Eplerenone – Suggested initial dose: 25 mg daily

Titration

Consider increasing dose of aldosterone antagonist at least every 2 weeks until maximum tolerated or target dose is achieved (EC):

  • Spironolactone – Suggested target dose: 25 mg daily or twice daily
  • Eplerenone – Suggested target dose: 50 mg daily

Monitoring

  • In patients with preserved renal function or mild to moderate renal impairment, renal function and potassium after initiation and titration should be assessed within 2 to 3 days and again at 7 days (EC).
  • Then, check monthly for 3 months and every 3 months afterwards (EC).
  • Clinical status may warrant closer monitoring (EC).

ACC/AHA Guideline Recommendations

  • Aldosterone receptor antagonists (or mineralocorticoid receptor antagonists) are recommended in patients with NYHA class II–IV HF and who have LVEF of 35% or less, unless contraindicated, to reduce morbidity and mortality. Patients with NYHA class II HF should have a history of prior cardiovascular hospitalization or elevated plasma natriuretic peptide levels to be considered for aldosterone receptor antagonists. Creatinine should be 2.5 mg/dL or less in men or 2.0 mg/dL or less in women (or estimated glomerular filtration rate >30 mL/min/1.73 m2), and potassium should be less than 5.0 mEq/L. Careful monitoring of potassium, renal function, and diuretic dosing should be performed at initiation and closely followed thereafter to minimize risk of hyperkalemia and renal insufficiency (I,A).
  • Aldosterone receptor antagonists are recommended to reduce morbidity and mortality following an acute MI in patients who have LVEF of 40% or less who develop symptoms of HF or who have a history of diabetes mellitus, unless contraindicated (III,B).
  • Inappropriate use of aldosterone receptor antagonists is potentially harmful because of life-threatening hyperkalemia or renal insufficiency when serum creatinine is greater than 2.5 mg/dL in men or greater than 2.0 mg/dL in women (or estimated glomerular filtration rate <30 mL/min/1.73m2), and/or potassium greater than 5.0 mEq/L (III, B).
  • Routine combined use of an ACE inhibitor, ARB, and aldosterone antagonist is potentially harmful for patients with HFrEF (III,C).