Chlorthalidone versus hydrochlorothiazide for hypertension - which is better for preventing CV events?

In the large pragmatic trial of thiazide diuretics at doses used commonly in clinical practice, the authors included adults 65 years of age or older who are patients in the Department of Veterans Affairs health system and had been getting hydrochlorothiazide at a daily 25 or 50 mg dose. 13,523 patients (mean age; 72 years) were randomly assigned to continue therapy with hydrochlorothiazide or switch to chlorthalidone at 12.5 or 25 mg daily.

The study's primary outcome was a composite of stroke, nonfatal myocardial infarction, heart failure leading to hospitalization, non–cancer-related death, and urgent coronary revascularization for unstable angina. A safety assessment was also done.

The authors reported the following findings:

• At baseline, hydrochlorothiazide at a daily dose of 25 mg had been prescribed in 94.5% of patients. Each group's mean baseline systolic blood pressure (BP) was 139 mm Hg.
• There was not much difference in the risk of primary-outcome events between the chlorthalidone group (10.4% patients) and the hydrochlorothiazide group (10.0% patients) (hazard ratio, 1.04) at a median follow-up of 2.4 years.
• The authors did not observe any between-group differences in the occurrence of any components of the primary outcome.
• Hypokalemia incidence was more significant in the chlorthalidone group compared to the hydrochlorothiazide group (6.0% vs. 4.4%).

To conclude, patients who were given chlorthalidone did not have a lower incidence of major cardiovascular outcome events or non–cancer-related deaths compared to patients who received hydrochlorothiazide.

Reference:

The study, "Chlorthalidone vs. Hydrochlorothiazide for Hypertension–Cardiovascular Events," was published in the New England Journal of Medicine. DOI: 10.1056/NEJMoa2212270