Why choose Spironolactone (SPIR) over Losartan (Angiotensin II Receptor Antagonist)?

From the Guidelines

Spironolactone is preferred over losartan in patients with heart failure with reduced ejection fraction, primary hyperaldosteronism, resistant hypertension, or edematous conditions, due to its effectiveness as a potassium-sparing diuretic and aldosterone antagonist, as shown in the RALES trial 1 and the EMPHASIS-HF trial 1. The choice between spironolactone and losartan depends on the specific clinical situation and the patient's condition.

• Spironolactone is particularly effective in patients with heart failure with reduced ejection fraction, as it has been shown to reduce the risk of death and hospitalization for heart failure, with a relative risk reduction (RRR) of 30% and an absolute risk reduction (ARR) of 11.4% 1.
• In patients with primary hyperaldosteronism, spironolactone is the preferred treatment due to its ability to block the effects of excess aldosterone.
• For patients with resistant hypertension, spironolactone may be added to existing treatment, as recommended in the 2024 ESC guidelines for the management of elevated blood pressure and hypertension 1.
• Losartan, an angiotensin II receptor blocker, may be preferred in patients who cannot tolerate spironolactone's side effects or who have conditions where ARBs show specific benefits, such as diabetic nephropathy. The typical starting dose of spironolactone is 25 mg daily, which can be titrated up to 100 mg daily based on response and potassium levels, as shown in Table 14 of the ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012 1. However, it requires careful monitoring of potassium levels and renal function, particularly in patients with kidney impairment or those taking other potassium-sparing medications, as noted in the 2024 ESC guidelines for the management of elevated blood pressure and hypertension 1 and the 2022 AHA/ACC/HFSA guideline for the management of heart failure 1. Side effects may include gynecomastia in men, menstrual irregularities in women, and hyperkalemia, as reported in the RALES trial 1 and the EMPHASIS-HF trial 1. In summary, spironolactone is the preferred choice over losartan in certain clinical situations, due to its effectiveness and benefits in reducing morbidity and mortality, as supported by the most recent and highest quality studies, including the 2024 ESC guidelines for the management of elevated blood pressure and hypertension 1 and the 2022 AHA/ACC/HFSA guideline for the management of heart failure 1.

From the FDA Drug Label

1 INDICATIONS AND USAGE

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. 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.

The choice of spironolactone over losartan may be due to the following reasons:

• Heart failure: Spironolactone is indicated for the treatment of NYHA Class III-IV heart failure, which may not be the primary indication for losartan.
• Hypertension: Spironolactone can be used as add-on therapy for hypertension, and its mechanism of action as a potassium-sparing diuretic may be beneficial in certain patients.
• Edema: Spironolactone is also indicated for the management of edema associated with hepatic cirrhosis or nephrotic syndrome, which may not be a primary indication for losartan. However, without more information about the specific patient and their condition, it is difficult to make a definitive statement about why spironolactone was chosen over losartan 2.

From the Research

Comparison of Spironolactone and Losartan

• Spironolactone is an aldosterone antagonist that has been shown to be effective in treating heart failure with reduced ejection fraction, resistant hypertension, and other conditions 3, 4, 5.
• Losartan, on the other hand, is an angiotensin II receptor antagonist that is commonly used to treat hypertension and heart failure 6.
• A study comparing the efficacy of spironolactone and eplerenone (another aldosterone antagonist) in resistant hypertension found that spironolactone was more effective, but eplerenone was better tolerated 6.
• There is no direct comparison between spironolactone and losartan in the provided studies, but spironolactone has been shown to be effective in patients with heart failure and resistant hypertension, while losartan is commonly used to treat these conditions.

Mechanism of Action

• Spironolactone works by antagonizing the effects of aldosterone, a hormone that promotes sodium and water retention in the body 3, 5.
• Losartan works by blocking the action of angiotensin II, a hormone that constricts blood vessels and increases blood pressure 6.
• The choice between spironolactone and losartan may depend on the specific condition being treated and the patient's individual needs and medical history.

Safety and Tolerability

• Spironolactone has been shown to be safe and effective in patients with heart failure and chronic kidney disease, but it can cause hyperkalemia (high potassium levels) in some patients 7.
• Losartan is generally well-tolerated, but it can cause side effects such as dizziness, headache, and cough 6.
• The safety and tolerability of spironolactone and losartan should be carefully considered when choosing between these medications.