What is the difference between Hydrochlorothiazide (HCTZ) and Chlorthalidone?

From the Guidelines

Chlorthalidone is generally preferred over HCTZ (hydrochlorothiazide) for the treatment of hypertension due to its longer duration of action and proven trial reduction of cardiovascular disease (CVD) 1.

Key Differences

• Chlorthalidone has a longer duration of action (up to 48-72 hours) compared to HCTZ (6-12 hours), allowing for once-daily dosing and potentially better 24-hour blood pressure control.
• The typical starting dose for chlorthalidone is 12.5 mg daily, which can be increased to 25 mg if needed, while the usual dose for HCTZ is 12.5-25 mg daily.
• Chlorthalidone has been shown to be more potent in lowering blood pressure and may provide better cardiovascular protection, as stated in the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults 1.

Considerations

• It's essential to monitor electrolytes, particularly potassium, more closely with chlorthalidone due to its increased potency.
• While both medications can cause similar side effects, such as electrolyte imbalances and increased uric acid levels, chlorthalidone may be associated with a slightly higher risk of these effects.
• In patients with a history of gout or electrolyte disturbances, HCTZ might be preferred.

Patient-Specific Factors

• The choice between chlorthalidone and HCTZ should be based on individual patient factors, including comorbidities, risk of side effects, and adherence considerations.
• As recommended by the American College of Cardiology/American Heart Association task force on clinical practice guidelines, chlorthalidone is preferred due to its prolonged half-life and proven trial reduction of CVD 1.

From the FDA Drug Label

Chlorthalidone is a monosulfamyl diuretic that differs chemically from thiazide diuretics in that a double-ring system is incorporated in its structure. Hydrochlorothiazide, USP is the 3,4-dihydro derivative of chlorothiazide.

The main difference between Hydrochlorothiazide (HCTZ) and Chlorthalidone is their chemical structure. Chlorthalidone has a double-ring system and is a monosulfamyl diuretic, whereas Hydrochlorothiazide is a thiazide diuretic with a different chemical structure.

• Molecular Formula: Chlorthalidone has a molecular formula of C14H11ClN2O4S, while Hydrochlorothiazide has a molecular formula of C7H8ClN3O4S2.
• Molecular Weight: Chlorthalidone has a molecular weight of 338.76, while Hydrochlorothiazide has a molecular weight of 297.74 2 3.

From the Research

Difference between Hydrochlorothiazide (HCTZ) and Chlorthalidone

• HCTZ and chlorthalidone are both thiazide diuretics used to treat hypertension, but they have some differences in terms of their effectiveness and safety profiles 4, 5, 6, 7, 8.
• In terms of blood pressure lowering, both HCTZ and chlorthalidone appear to be effective, but some studies suggest that chlorthalidone may be more effective in preventing cardiovascular disease events 4, 5.
• However, other studies have found no significant difference in the results of patients treated with HCTZ versus those treated with chlorthalidone 6, 7, 8.
• Chlorthalidone has been associated with a greater incidence of electrolyte abnormalities, particularly hypokalemia, compared to HCTZ 6, 7, 8.
• The American College of Cardiology recommends chlorthalidone over HCTZ as a first-line treatment for hypertension, but some studies suggest that HCTZ may be a better option due to its safer side effect profile 5, 7.

Effectiveness

• Both HCTZ and chlorthalidone have been shown to be effective in lowering blood pressure and reducing the risk of cardiovascular disease events 4, 5, 6, 7, 8.
• However, the evidence is not conclusive, and some studies suggest that chlorthalidone may be more effective in certain populations, such as older adults 6.
• A head-to-head study comparing the effectiveness of HCTZ and chlorthalidone in terms of hard clinical outcomes may be needed to resolve the debate 4.

Safety

• Both HCTZ and chlorthalidone have been associated with hypokalemia, but chlorthalidone has been shown to have a higher risk of electrolyte abnormalities, particularly hypokalemia 6, 7, 8.
• Chlorthalidone has also been associated with a higher risk of acute renal failure, chronic kidney disease, and type 2 diabetes mellitus compared to HCTZ 7.
• However, chlorthalidone has been shown to have a lower risk of diagnosed abnormal weight gain compared to HCTZ 7.