From the Guidelines
Spironolactone is indicated for patients with moderate to severe systolic heart failure (left ventricular ejection fraction ≤35%) who remain symptomatic despite standard therapy with ACE inhibitors and beta-blockers. The typical starting dose is 25 mg once daily, which may be titrated up to 50 mg daily if needed and tolerated, as shown in the EMPHASIS-HF trial 1. Patients should be monitored for hyperkalemia, especially those with renal impairment or diabetes, with potassium levels checked within 1 week of initiation and dose changes, then periodically thereafter. Some key points to consider when prescribing spironolactone include:
- Checking serum potassium and creatinine levels before initiating therapy, as well as after 4-6 days, to minimize the risk of hyperkalemia 1
- Starting with a low dose (25 mg daily) and titrating up to 50 mg daily if symptoms persist and normokalemia exists 1
- Reducing the dose by 50% or stopping the medication if serum potassium levels exceed 5.5 mmol/L 1 Spironolactone works as an aldosterone antagonist, blocking mineralocorticoid receptors which reduces sodium and water retention while preserving potassium. This mechanism helps counteract the harmful effects of elevated aldosterone levels in heart failure, including myocardial fibrosis and vascular remodeling. The medication has been shown to reduce mortality, hospitalization rates, and improve symptoms in appropriate candidates, with a relative risk reduction in death of 30% and a relative risk reduction in hospitalization for worsening heart failure of 35% in the RALES trial 1. Common side effects include gynecomastia in men, menstrual irregularities in women, and the aforementioned risk of hyperkalemia. It is essential to carefully select patients and monitor them closely to minimize the risks associated with spironolactone therapy, as supported by the European Society of Cardiology guidelines 1.
From the FDA Drug Label
Spironolactone tablets are indicated for treatment of NYHA Class III-IV heart failure and reduced ejection fraction to increase survival, manage edema, and reduce the need for hospitalization for heart failure. The answer to when spironolactone is indicated for systolic heart failure is:
- NYHA Class III-IV heart failure
- reduced ejection fraction 2
From the Research
Indications for Spironolactone in Systolic Heart Failure
- Spironolactone is indicated for patients with systolic heart failure who have New York Heart Association (NYHA) class III or IV symptoms despite maximal therapies with ACE inhibitors, beta-blockers, diuretics, and digoxin 3.
- The use of spironolactone is recommended in systolic heart failure (HF) patients that have been in NYHA class III or IV, as shown in the Randomized Aldactone Evaluation Study (RALES) 4.
- Spironolactone can be used to enhance the efficacy of diuretic + ACE inhibitor combinations in patients with severe heart failure, reducing overall mortality and the incidence of hospitalization for heart disease and disability 5.
Patient Selection and Monitoring
- Patients should have serum potassium (K+) < or = 5 meq/L and serum creatinine (Cr) < or = 2.5 mg/dL before initiating spironolactone therapy 4.
- Spironolactone should be withdrawn if serum K+ > or = 5.5 meq/L, serum Cr increases more than 30%-50% of the baseline value, and/or if the patient has gynecomastia 4.
- Patients with chronic kidney disease (CKD) stages 3-5 can be considered for spironolactone therapy, but careful monitoring of potassium levels and renal function is necessary 6.
Safety and Efficacy
- Spironolactone has been shown to improve clinical state and functional class of patients with moderate and severe chronic heart failure receiving optimal therapy 7.
- Long-term therapy with spironolactone can block processes of desadaptive left ventricular remodeling and improve left ventricular contractile function 7.
- However, spironolactone can cause side effects such as hyperkalemia, gynecomastia, and renal function deterioration, which require close monitoring 4, 5, 7, 6.