Background Whether chlorthalidone is superior to hydrochlorothiazide for preventing major adverse cardiovascular events in patients with hypertension is unclear. Methods In a pragmatic trial, we randomly assigned adults 65 years of age or older who were patients in the Department of Veterans Affairs health system and had been receiving hydrochlorothiazide at a daily dose of 25 or 50 mg to continue therapy with hydrochlorothiazide or to switch to chlorthalidone at a daily dose of 12.5 or 25 mg. The primary outcome was a composite of nonfatal myocardial infarction, stroke, heart failure resulting in hospitalization, urgent coronary revascularization for unstable angina, and non-cancer-related death. Safety was also assessed. Results A total of 13,523 patients underwent randomization. The mean age was 72 years. At baseline, hydrochlorothiazide at a dose of 25 mg per day had been prescribed in 12,781 patients (94.5%). The mean baseline systolic blood pressure in each group was 139 mm Hg. At a median follow-up of 2.4 years, there was little difference in the occurrence of primary-outcome events between the chlorthalidone group (702 patients [10.4%]) and the hydrochlorothiazide group (675 patients [10.0%]) (hazard ratio, 1.04; 95% confidence interval, 0.94 to 1.16; P=0.45). There were no between-group differences in the occurrence of any of the components of the primary outcome. The incidence of hypokalemia was higher in the chlorthalidone group than in the hydrochlorothiazide group (6.0% vs. 4.4%, P<0.001). Conclusions In this large pragmatic trial of thiazide diuretics at doses commonly used in clinical practice, patients who received chlorthalidone did not have a lower occurrence of major cardiovascular outcome events or non-cancer-related deaths than patients who received hydrochlorothiazide. (Funded by the Veterans Affairs Cooperative Studies Program; ClinicalTrials.gov number, NCT02185417.)
|Original language||English (US)|
|Number of pages||10|
|Journal||New England Journal of Medicine|
|State||Published - Dec 29 2022|
Bibliographical noteFunding Information:
The Supported by the Veterans Affairs Cooperative Studies Program through a grant to the Diuretic Comparison Project.
© 2022 Massachusetts Medical Society.
- Cardiology General
- Clinical Medicine
- Clinical Medicine General
- Geriatrics/Aging General
- Nephrology General
PubMed: MeSH publication types
- Comparative Study
- Journal Article
- Pragmatic Clinical Trial
- Randomized Controlled Trial
- Research Support, U.S. Gov't, P.H.S.