Whether chlorthalidone is superior to hydrochlorothiazide in preventing major cardiovascular events in patients with hypertension is unclear.
In a pragmatic trial, we randomly assigned adults aged 65 years and older who were patients of the Department of Veterans Affairs health system and receiving hydrochlorothiazide at a dose of 25 or 50 mg daily to continue hydrochlorothiazide therapy or switch to chlorthalidone. 12.5 or 25 mg per day. The primary outcome was nonfatal myocardial infarction, stroke, heart failure resulting in hospitalization, urgent coronary revascularization for unstable angina, and noncomposite cancer-related death. Safety was also assessed.
A total of 13,523 patients were randomized. The average age was 72 years. At baseline, 12,781 patients (94.5%) were prescribed hydrochlorothiazide at a dose of 25 mg per day. The mean baseline systolic blood pressure in each group was 139 mm Hg. At a mean follow-up of 2.4 years, there was little difference in the occurrence of primary 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 differences between groups in the occurrence of any component 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).
In this large pragmatic trial of thiazide diuretic doses commonly used in clinical practice, patients who received chlorthalidone had no more major cardiovascular events or cancer-related deaths than patients who received hydrochlorothiazide. (Funded by the Veterans Affairs Cooperative Study Program; ClinicalTrials.gov number, NCT02185417.)