What is the best evidence-based potassium-sparing diuretic, spironolactone or eplerenone, for a 78-year-old lady with left ventricular (LV) impairment, an ejection fraction (EF) of 40%, and hypokalemia, following a recent Transcatheter Aortic Valve Implantation (TAVI) procedure, to replace furosemide?

From the Guidelines

Spironolactone would be the best evidence-based choice for this 78-year-old post-TAVI patient with LV impairment (EF 40%) and hypokalemia. Start with spironolactone 25 mg daily, which can be titrated up to 50 mg daily if needed and tolerated. The RALES trial demonstrated that spironolactone significantly reduces mortality in heart failure patients with reduced ejection fraction, with a 30% reduction in all-cause mortality 1. While eplerenone is also effective and has fewer anti-androgenic side effects (such as gynecomastia), spironolactone has more robust evidence specifically in heart failure with reduced ejection fraction and is more cost-effective.

When initiating spironolactone, monitor serum potassium levels closely, particularly within the first week and after any dose adjustments. Target potassium levels between 4.0-5.0 mmol/L. Also monitor renal function, as deterioration may occur, especially in elderly patients. If the patient develops hyperkalemia (>5.5 mmol/L) or significant renal dysfunction, reduce the dose or discontinue the medication. Spironolactone works by blocking aldosterone receptors, reducing sodium reabsorption and potassium excretion in the distal tubule, which helps maintain potassium levels while providing diuresis and beneficial neurohormonal modulation in heart failure.

Some key points to consider when using spironolactone in this patient population include:

• Avoiding the use of spironolactone in patients with serum creatinine >2.5 mg/dL, or serum K+ >5.0 mmol/L 1
• Monitoring for signs of hyperkalemia, such as muscle weakness, palpitations, and arrhythmias
• Adjusting the dose of spironolactone based on renal function and potassium levels
• Considering the use of eplerenone as an alternative, especially in patients with a history of gynecomastia or other anti-androgenic side effects.

Overall, the use of spironolactone in this patient population has been shown to improve outcomes and reduce morbidity and mortality, making it a valuable addition to the treatment regimen for heart failure with reduced ejection fraction.

From the FDA Drug Label

The eplerenone post-acute myocardial infarction heart failure efficacy and survival study (EPHESUS) was a multinational, multicenter, double-blind, randomized, placebo-controlled study in patients clinically stable 3 to 14 days after an acute MI with LV dysfunction (as measured by left ventricular ejection fraction [LVEF] ≤40%) and either diabetes or clinical evidence of HF Patients randomized to eplerenone were given an initial dose of 25 mg once daily and titrated to the target dose of 50 mg once daily after 4 weeks if serum potassium was <5. 0 mEq/L.

The best evidence-based choice for a potassium-sparing diuretic in this patient is eplerenone.

• The EPHESUS study 2 showed that eplerenone reduced the risk of death from any cause by 15% in patients with LV dysfunction (LVEF ≤40%) after an acute MI.
• The study population had similar characteristics to the patient, including LV dysfunction and a history of cardiovascular disease.
• Eplerenone was well-tolerated and effective in reducing mortality and morbidity in this population.
• There is no direct comparison with spironolactone in the provided drug label, so eplerenone is the best choice based on the available evidence.

From the Research

Potassium-Sparing Diuretics for Hypokalemia

• The patient's hypokalemia is likely caused by furosemide therapy, as evidenced by studies showing that furosemide can lead to hypokalemia 3, 4.
• To manage hypokalemia, potassium-sparing diuretics such as spironolactone or eplerenone can be considered.
• However, the provided studies do not directly compare the effectiveness of spironolactone and eplerenone in patients with hypokalemia and left ventricular impairment after TAVI.

Considerations for Spironolactone and Eplerenone

• Spironolactone is a potassium-sparing diuretic that has been shown to be effective in managing heart failure and reducing mortality 5.
• Eplerenone is another potassium-sparing diuretic that has been shown to be effective in managing heart failure and reducing mortality, with a more favorable side effect profile compared to spironolactone.
• The choice between spironolactone and eplerenone may depend on individual patient factors, such as renal function and comorbidities.

Lack of Direct Evidence

• There are no studies provided that directly compare the effectiveness of spironolactone and eplerenone in patients with hypokalemia and left ventricular impairment after TAVI.
• The provided studies focus on the management of heart failure, hypokalemia, and the use of furosemide, but do not provide direct evidence for the use of potassium-sparing diuretics in this specific patient population 6, 7.