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Chlorthalidone and hydrochlorothiazide have comparable 3-year major adverse cardiovascular event rates in hypertensive patients. Novelty: ClaimNovelty.CONFIRMATORY. Consensus alignment: ConsensusAlignment.SUPPORTS_CONSENSUS.

February 6, 2026

Comparison of cardiovascular outcomes between chlorthalidone and hydrochlorothiazide in hypertensive patients

Key Result

Chlorthalidone and hydrochlorothiazide had similar 3-year MACE rates (1.2% vs 1.4%, HR 0.91, p=0.77) and safety profiles in hypertensive patients.

Key Points

The study aims to compare the cardiovascular outcomes between chlorthalidone and hydrochlorothiazide in hypertensive patients.
Conducted a multicenter retrospective cohort study using electronic health records.
Included 14,257 hypertensive patients treated with either chlorthalidone or hydrochlorothiazide.
Matched patients 1:1 using propensity scores for balanced comparison.
Analyzed demographic characteristics, incidence of major adverse cardiovascular events, and safety profiles.
The 3-year incidence of major adverse cardiovascular events was 1.2% for chlorthalidone and 1.4% for hydrochlorothiazide.
No significant difference in cardiovascular mortality, both at 0.2%.
Myocardial infarction rates were 0.3% in chlorthalidone users vs. 0.4% in hydrochlorothiazide users.
Hypokalemia occurred in 19.2% of the chlorthalidone group compared to 16.7% in the hydrochlorothiazide group.

Structured PICO

Does chlorthalidone improve cardiovascular outcomes compared to hydrochlorothiazide in hypertensive patients?

Population

14,257 hypertensive patients (propensity matched to 1,606 per group), mean age 61.8, 59.3% male.

Intervention

Chlorthalidone

Comparator

Hydrochlorothiazide (1:1 propensity score matched)

Outcome

Major adverse cardiovascular events (MACE) at 3 yearscomposite

In hypertensive patients, chlorthalidone and hydrochlorothiazide demonstrated comparable 3-year cardiovascular outcomes and safety profiles.

Main Result

Absolute Event Rate: 0% vs 0%

Abstract

Abstract Background Chlorthalidone and hydrochlorothiazide are widely used thiazide diuretics for hypertension management. This study aimed to evaluate and compare the cardiovascular outcomes of patients treated with chlorthalidone versus hydrochlorothiazide. Methods This multicenter retrospective cohort study utilized data from our medical center, derived from electronic health records. A total of 14,257 hypertensive patients treated with either chlorthalidone (n = 1,920) or hydrochlorothiazide (n = 12,337) were identified. Patients were matched 1:1 using propensity scores, resulting in 1,606 patients in each treatment group. Demographic and clinical characteristics, incidence of major adverse cardiovascular events (MACE), and safety profiles were analyzed. Results Baseline characteristics after propensity score matching were well balanced between the two groups. The average age was 61.8 ± 14.6 years for chlorthalidone users, with 59.3% being male. The 3-year MACE occurred in 1.2% of the chlorthalidone group compared with 1.4% of the hydrochlorothiazide group (hazard ratio 0.91, p = 0.77). For secondary outcomes, cardiovascular mortality was 0.2% in both groups (p = 0.92). Myocardial infarction occurred in 0.3% of chlorthalidone users and 0.4% of hydrochlorothiazide users (p = 0.65). The incidence of hypokalemia was 19.2% in the chlorthalidone group versus 16.7% in the hydrochlorothiazide group (p = 0.07). Conclusions In hypertensive patients, chlorthalidone and hydrochlorothiazide showed comparable cardiovascular outcomes and safety profiles.

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