Chlorthalidone vs. Hydrochlorothiazide for Hypertension–Cardiovascular Events

This pragmatic, multicenter trial the Diuretic Comparison Project, compared chlorthalidone and hydrochlorothiazide in preventing major cardiovascular events among 13,523 patients aged 65 or older with hypertension receiving VA care. Participants already prescribed hydrochlorothiazide (mostly 25 mg daily) were randomized to continue it or switch to chlorthalidone (12.5–25 mg daily). Over a median 2.4 years, the primary composite outcome (nonfatal myocardial infarction, stroke, hospitalization for heart failure, urgent coronary revascularization, and non-cancer-related death) occurred in 10.4% of the chlorthalidone group vs. 10.0% of the hydrochlorothiazide group (HR: 1.04; 95% CI: 0.94–1.16; P=0.45), showing no significant difference. Subgroup analysis suggested patients with prior MI or stroke may benefit more from chlorthalidone (HR: 0.73), but the overall trial showed no superiority. Hypokalemia and potassium supplementation were slightly more frequent in the chlorthalidone group. Both medications were similarly effective at blood pressure control. The study concludes that at commonly used doses, chlorthalidone does not outperform hydrochlorothiazide in cardiovascular protection, supporting continued use of either agent in routine care.

This pragmatic, multicenter trial the Diuretic Comparison Project, compared chlorthalidone and hydrochlorothiazide in preventing major cardiovascular events among 13,523 patients aged 65 or older with hypertension receiving VA care. Participants already prescribed hydrochlorothiazide (mostly 25 mg daily) were randomized to continue it or switch to chlorthalidone (12.5–25 mg daily). Over a median 2.4 years, the primary composite outcome (nonfatal myocardial infarction, stroke, hospitalization for heart failure, urgent coronary revascularization, and non-cancer-related death) occurred in 10.4% of the chlorthalidone group vs. 10.0% of the hydrochlorothiazide group (HR: 1.04; 95% CI: 0.94–1.16; P=0.45), showing no significant difference. Subgroup analysis suggested patients with prior MI or stroke may benefit more from chlorthalidone (HR: 0.73), but the overall trial showed no superiority. Hypokalemia and potassium supplementation were slightly more frequent in the chlorthalidone group. Both medications were similarly effective at blood pressure control. The study concludes that at commonly used doses, chlorthalidone does not outperform hydrochlorothiazide in cardiovascular protection, supporting continued use of either agent in routine care.