Chlorthalidone vs. Hydrochlorothiazide for Hypertension-Cardiovascular Events

Area of Science:

• Cardiology
• Pharmacology
• Clinical Trials

Background:

• The comparative effectiveness of chlorthalidone and hydrochlorothiazide for major adverse cardiovascular events (MACE) in hypertension management remains unclear.
• Thiazide diuretics are a cornerstone in hypertension treatment, necessitating clear guidance on optimal agent selection.

Purpose of the Study:

• To compare the efficacy of chlorthalidone versus hydrochlorothiazide in preventing MACE in older adults with hypertension.
• To assess the safety profiles of chlorthalidone and hydrochlorothiazide in the target patient population.

Main Methods:

• A pragmatic randomized trial involving 13,523 adults aged 65+ with hypertension, previously on hydrochlorothiazide.
• Participants were randomized to continue hydrochlorothiazide or switch to chlorthalidone at standard doses.
• The primary outcome was a composite of cardiovascular events and non-cancer-related death, with safety monitoring.

Main Results:

• No significant difference in the primary composite outcome was observed between the chlorthalidone group (10.4%) and the hydrochlorothiazide group (10.0%) after a median follow-up of 2.4 years (HR, 1.04; 95% CI, 0.94-1.16).
• Individual components of the primary outcome did not differ significantly between the groups.
• The incidence of hypokalemia was significantly higher in the chlorthalidone group (6.0%) compared to the hydrochlorothiazide group (4.4%).

Conclusions:

• In this large pragmatic trial, chlorthalidone did not demonstrate superior efficacy over hydrochlorothiazide in reducing major cardiovascular outcomes or non-cancer-related deaths.
• The findings suggest that commonly used doses of these thiazide diuretics offer comparable cardiovascular protection, but chlorthalidone is associated with a higher risk of hypokalemia.