Is indapamide better than hydrochlorothiazide (HCTZ)?

From the Guidelines

Indapamide is generally considered better than hydrochlorothiazide for most patients needing a thiazide-like diuretic.

Key Points

• Indapamide is more potent at lower doses (typically 1.25-2.5mg daily) and has a longer duration of action, allowing once-daily dosing 1.
• It demonstrates better metabolic profiles with fewer adverse effects on glucose, lipids, and electrolytes compared to hydrochlorothiazide (typically dosed at 12.5-25mg daily) 1.
• Studies have shown indapamide to be more effective at lowering blood pressure, particularly systolic pressure, and it appears to provide better cardiovascular protection and reduction in stroke risk 1.
• Indapamide also has less impact on potassium levels, reducing the risk of hypokalemia compared to hydrochlorothiazide 1.
• The improved metabolic profile makes indapamide particularly beneficial for patients with diabetes or metabolic syndrome.

Considerations

• Individual patient factors, including cost, availability, and specific comorbidities, should guide the final choice between these medications.
• Both medications still require monitoring of electrolytes, particularly potassium, sodium, and magnesium levels, especially during the initial treatment period 1.
• The choice between indapamide and hydrochlorothiazide should be based on the most recent and highest quality evidence, with consideration of the patient's overall health status and medical history 1.

From the FDA Drug Label

In long-term controlled clinical trials comparing the hypokalemic effects of daily doses of indapamide and hydrochlorothiazide, however, 47% of patients receiving indapamide 2.5 mg, 72% of patients receiving indapamide 5 mg, and 44% of patients receiving hydrochlorothiazide 50 mg had at least one potassium value (out of a total of 11 taken during the study) below 3.5 mEq/L.

The FDA drug label does not provide sufficient information to conclude that indapamide is better than hydrochlorothiazide (HCTZ) overall. However, it can be noted that:

• Hypokalemia incidence: Indapamide 2.5 mg had a lower incidence of hypokalemia (47%) compared to indapamide 5 mg (72%), but a higher incidence compared to hydrochlorothiazide 50 mg (44%) 2. It is essential to consider that the provided information only compares the hypokalemic effects of indapamide and hydrochlorothiazide, and does not provide a comprehensive comparison of the two drugs.

From the Research

Comparison of Indapamide and Hydrochlorothiazide

• Indapamide and hydrochlorothiazide (HCTZ) are both used to treat hypertension, but studies suggest they have different effects on cardiovascular outcomes and renal function 3, 4, 5, 6.
• A study published in 2017 found that indapamide and chlorthalidone reduce cardiovascular morbidity and mortality, while HCTZ does not have beneficial effects on these outcomes 3.
• Another study from 1995 compared the effects of indapamide and HCTZ on creatinine clearance in patients with impaired renal function and hypertension, and found that indapamide was associated with a 28.5% increase in creatinine clearance, while HCTZ was associated with a 17.4% decrease 4.
• A 2000 study compared the effects of indapamide and HCTZ on plasma lipids and lipoproteins in hypertensive patients, and found that both drugs had similar effects on blood pressure and serum potassium, but indapamide was associated with a significant increase in triglyceride levels 7.
• A 2015 review of evidence-based diuretics found that chlorthalidone and indapamide have more evidence for reducing morbidity and mortality than HCTZ, and recommended that they be considered first-choice thiazide-like diuretics 5.
• A 2017 study compared the effects of hydrochlorothiazide and indapamide on the kidney in hypertensive patients inadequately controlled with losartan, and found that indapamide was superior to hydrochlorothiazide in improving renal tubular injury and renal hemodynamics 6.

Key Findings

• Indapamide may be a better choice than HCTZ for patients with hypertension, particularly those with impaired renal function 3, 4, 6.
• Indapamide and HCTZ have different effects on cardiovascular outcomes and renal function, with indapamide appearing to have more beneficial effects 3, 4, 5, 6.
• The choice of diuretic should be based on individual patient needs and characteristics, as well as the available evidence 3, 5.