Diuretic Comparison Project
Trial question
Is chlorthalidone superior to hydrochlorothiazide for the prevention of CV events in patients with hypertension?
Study design
Multi-center
Open label
RCT
Population
Characteristics of study participants
3.0% female
97.0% male
N = 13523
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
Composite outcome of nonfatal MI, stroke, heart failure resulting in hospitalization, urgent coronary revascularization for unstable angina, and non-cancer-related death
10.4%
10%
10.4 %
7.8 %
5.2 %
2.6 %
0.0 %
Chlorthalidone
Hydrochlorothiazide
No significant
difference ↔
No significant difference in composite outcome of nonfatal MI, 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 MI (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 MI, 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.
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