Since it remains unclear if chlorthalidone is superior to hydrochlorothiazide in averting major adverse cardiovascular events in patients with hypertension, a recent pragmatic trial randomized adults (65 years of age or older) who had been receiving hydrochlorothiazide at a daily dose of 25 or 50 mg to continue therapy with hydrochlorothiazide or switch to chlorthalidone at a daily dose of 12.5 or 25 mg to assess the difference. 

After a median follow-up of 2.4 years, the investigators observed a little difference in the occurrence of primary-outcome events between the chlorthalidone group (10.4%) and the hydrochlorothiazide group (10.0%) and no between-group differences concerning the occurrence of any of the components of the primary outcome (composite of nonfatal myocardial infarction, stroke, heart failure resulting in hospitalization, urgent coronary revascularization for unstable angina, and non–cancer-related death). Furthermore, they observed a higher hypokalemia incidence in the chlorthalidone group than in the hydrochlorothiazide group.

Reference-Ishani A, Cushman W, Leatherman S. et al. Chlorthalidone vs. Hydrochlorothiazide for Hypertension–Cardiovascular Events. N Engl J Med 2022; 387:2401-2410. DOI: 10.1056/NEJMoa2212270