Thiazide-like versus Thiazide Diuretics — Finally, an Answer

This editorial evaluates the Diuretic Comparison Project (DCP)—a pragmatic, randomized trial comparing chlorthalidone and hydrochlorothiazide in 13,523 older adults treated for hypertension within the U.S. Veterans Affairs system. Patients already receiving hydrochlorothiazide were randomized to continue therapy or switch to chlorthalidone. Over a median follow-up of 2.4 years, the primary composite endpoint—nonfatal myocardial infarction, stroke, heart failure hospitalization, unstable angina revascularization, or non-cancer death—occurred similarly in both groups (10.4% vs. 10.0%; HR: 1.04; 95% CI: 0.94–1.16), with no statistically significant difference. Chlorthalidone was associated with more hypokalemia and potassium supplementation, reflecting its longer half-life and higher potency. Although subgroup analysis hinted at benefit among patients with prior cardiovascular disease, the overall findings suggest therapeutic equivalence between the agents. The editorial emphasizes the trial's significance as a cost-effective, high-quality model of point-of-care comparative effectiveness research, while noting limitations such as underpowered outcome rates, dose mismatches, and low monotherapy prevalence.

This editorial evaluates the Diuretic Comparison Project (DCP)—a pragmatic, randomized trial comparing chlorthalidone and hydrochlorothiazide in 13,523 older adults treated for hypertension within the U.S. Veterans Affairs system. Patients already receiving hydrochlorothiazide were randomized to continue therapy or switch to chlorthalidone. Over a median follow-up of 2.4 years, the primary composite endpoint—nonfatal myocardial infarction, stroke, heart failure hospitalization, unstable angina revascularization, or non-cancer death—occurred similarly in both groups (10.4% vs. 10.0%; HR: 1.04; 95% CI: 0.94–1.16), with no statistically significant difference. Chlorthalidone was associated with more hypokalemia and potassium supplementation, reflecting its longer half-life and higher potency. Although subgroup analysis hinted at benefit among patients with prior cardiovascular disease, the overall findings suggest therapeutic equivalence between the agents. The editorial emphasizes the trial's significance as a cost-effective, high-quality model of point-of-care comparative effectiveness research, while noting limitations such as underpowered outcome rates, dose mismatches, and low monotherapy prevalence.