6/28/23, 1:21 AM Diuretic Comparison Project Pathway Feedback Search Clinical Topics Home Studies Diuretic Comparison Project Diuretic Comparison Project Disease Hypertension Trial question Is chlorthalidone superior to hydrochlorothiazide for the prevention of cardiovascular events in patients with hypertension? Study design Multi-center Open label RCT Population Characteristics of study participants 3.0% female N = 13523 97.0% male 13523 patients (431 female, 13092 male) Inclusion criteria: adult patients 65 years of age receiving hydrochlorothiazide at a dose of 25-50 mg/day Key exclusion criteria: receipt of blood-pressure medication containing hydrochlorothiazide combined with other agents Interventions N=6756 chlorthalidone (at a daily dose of 12.5-25 mg) N=6767 hydrochlorothiazide (at a daily dose of 25-50 mg) Primary outcome https://web.pathway.md/studies/recd7zuj6v0ZbxVVw 1/2 6/28/23, 1:21 AM Diuretic Comparison Project Pathway Composite outcome of nonfatal myocardial infarction, stroke, heart failure resulting in hospitalization, urgent coronary revascularization for unstable angina, and non-cancer-related death 10.4 % 10.4 10 7.8 % 5.2 % 2.6 % No significant difference 0.0 % Chlorthalidone Hydrochlorothiazide No significant difference in composite outcome of nonfatal myocardial infarction, stroke, HF resulting in hospitalization, urgent coronary revascularization for unstable angina, and non-cancer- related death (10.4% vs. 10%; HR 1.04, 95% CI 0.94 to 1.16) Secondary outcomes No significant difference in myocardial infarction (2.1% vs. 2.1%; HR 1.02, 95% CI 0.8 to 1.28) No significant difference in hospitalization due to HF (3.6% vs. 3.4%; HR 1.04, 95% CI 0.87 to 1.25) No significant difference in non-cancer-related death (5.3% vs. 5.2%; HR 1.01, 95% CI 0.88 to 1.17) Safety outcomes No significant difference in hospitalization for any cause. Significant difference in hypokalemia (6.0% vs. 4.4%). Conclusion In adult patients 65 years of age receiving hydrochlorothiazide at a dose of 25-50 mg/day, chlorthalidone was not superior to hydrochlorothiazide with respect to the composite outcome of nonfatal myocardial infarction, stroke, HF resulting in hospitalization, urgent coronary revascularization for unstable angina, and non-cancer-related death. Reference Areef Ishani, William C Cushman, Sarah M Leatherman et al. Chlorthalidone vs. Hydrochlorothiazide for Hypertension-Cardiovascular Events. N Engl J Med. 2022 Dec 29;387(26):2401-2410. Open reference URL https://web.pathway.md/studies/recd7zuj6v0ZbxVVw 2/2