What is the role of Spironolactone (a potassium-sparing diuretic) in managing hypertension (high blood pressure)?

From the Guidelines

Spironolactone is recommended for the treatment of resistant hypertension, as it has been shown to provide substantial blood pressure reduction when added to multidrug regimens, as evidenced by the 2024 ESC guidelines 1. The use of spironolactone in treating high blood pressure is based on its mechanism of action, which involves blocking the hormone aldosterone, leading to increased sodium and water excretion and potassium conservation. This results in a reduction in blood volume and subsequently lowers blood pressure.

Key Points to Consider

• Spironolactone is particularly effective in patients with resistant hypertension, where other medications have failed to achieve adequate blood pressure control 1.
• The medication is typically prescribed at doses of 25-100 mg daily, with the dose often being gradually increased as needed 1.
• As a potassium-sparing diuretic, spironolactone can cause high potassium levels, making regular blood tests necessary to monitor potassium, sodium, and kidney function 1.
• Other potential side effects of spironolactone include breast tenderness in men (gynecomastia), irregular menstruation in women, and decreased sexual desire, due to its effects on hormone levels 1.
• Patients taking spironolactone should avoid consuming high-potassium foods and supplements to minimize the risk of hyperkalemia 1.

Clinical Evidence

The 2024 ESC guidelines 1 recommend the use of spironolactone as a fourth-line treatment for resistant hypertension, after maximally tolerated triple-combination therapy with a RAS blocker, CCB, and diuretic. The guidelines also suggest that spironolactone may be considered as an alternative to beta-blockers in patients who do not have a compelling indication for beta-blocker therapy 1.

Comparison with Other Studies

While the 2018 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline 1 also supports the use of spironolactone in treating resistant hypertension, the 2024 ESC guidelines 1 provide more recent and specific recommendations for its use in this context.

Conclusion Not Applicable - Direct Answer Only

The use of spironolactone in treating high blood pressure is supported by the most recent clinical guidelines, which recommend its use as a fourth-line treatment for resistant hypertension 1.

From the FDA Drug Label

Spironolactone tablets are indicated as add-on therapy for the treatment of hypertension, to lower blood pressure in patients who are not adequately controlled on other agents. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions The dose response of spironolactone for hypertension has not been well characterized. In patients with hypertension, decreases in systolic blood pressure have been observed at doses ranging from 25 mg/day to 100 mg/day.

Spironolactone is used to treat hypertension as an add-on therapy to lower blood pressure in patients not adequately controlled on other agents. The goal is to reduce the risk of cardiovascular events, such as strokes and myocardial infarctions. The exact dose response for hypertension is not well characterized, but decreases in systolic blood pressure have been observed at doses ranging from 25 mg/day to 100 mg/day 2, 2.

From the Research

Mechanism of Action

• Spironolactone is a potassium-sparing diuretic with anti-aldosterone effects, which are beneficial in the management of hypertension 3.
• The anti-aldosterone effects of spironolactone lead to a decrease in blood pressure by reducing the amount of fluid in the blood vessels and increasing the excretion of sodium and water in the urine.

Efficacy in Resistant Hypertension

• Spironolactone has been shown to be effective in reducing blood pressure in patients with resistant hypertension, with an average reduction of 22/10 mmHg in systolic and diastolic blood pressure 3.
• A study found that low-dose spironolactone (25 mg/day) reduced blood pressure in patients with resistant hypertension and type 2 diabetes mellitus, with a significant reduction in daytime blood pressure and urinary albumin excretion 4.
• Another study found that spironolactone monotherapy lowered blood pressure compared to placebo, with a reduction of 20.09 mmHg in systolic blood pressure and 6.75 mmHg in diastolic blood pressure 5.

Safety and Adverse Effects

• The use of spironolactone in patients with resistant hypertension requires careful monitoring of serum potassium levels, as it can cause hyperkalemia, particularly when combined with other medications that increase potassium levels 6.
• Other adverse effects of spironolactone include gynecomastia, renal insufficiency, and dehydration 6, 3.
• A daily dose of 25 mg of spironolactone is recommended, as higher doses may increase the risk of adverse effects without providing additional benefits 6, 5.

Clinical Use

• Spironolactone is considered a fourth-line therapy for hypertension in patients already treated with multiple medications 5.
• It is essential to rule out secondary causes of hypertension before initiating spironolactone therapy in patients with resistant hypertension 3.
• Spironolactone may be an appropriate addition to the treatment regimen for patients with resistant hypertension who are not at their blood pressure goal, despite being treated with multiple antihypertensive medications 3, 4.