Chlorthalidone versus hydrochlorothiazide for the treatment of hypertension in older adults: a population-based cohort study

Abstract

Background: Some evidence suggests that chlorthalidone may be superior to hydrochlorothiazide for the treatment of hypertension.

Objective: To compare the effectiveness and safety of chlorthalidone and hydrochlorothiazide in older adults.

Design: Propensity score-matched observational cohort study with up to 5 years of follow-up.

Setting: Ontario, Canada.

Patients: All individuals aged 66 years or older who were newly treated with chlorthalidone or hydrochlorothiazide and were not hospitalized for heart failure, stroke, or myocardial infarction in the prior year were eligible for inclusion. Each chlorthalidone recipient was matched to up to 2 hydrochlorothiazide recipients on the basis of age, sex, year of treatment initiation, and propensity score.

Measurements: The primary outcome was a composite of death or hospitalization for heart failure, stroke, or myocardial infarction. Safety outcomes included hospitalization with hypokalemia or hyponatremia.

Results: A total of 29 873 patients were studied. During follow-up, chlorthalidone recipients (n = 10 384) experienced the primary outcome at a rate of 3.2 events per 100 person-years of follow-up, and hydrochlorothiazide recipients experienced 3.4 events per 100 person-years of follow-up (adjusted hazard ratio, 0.93 [95% CI, 0.81 to 1.06]). Patients treated with chlorthalidone were more likely to be hospitalized with hypokalemia (adjusted hazard ratio, 3.06 [CI, 2.04 to 4.58]) or hyponatremia (adjusted hazard ratio, 1.68 [CI, 1.24 to 2.28]). In 9 post hoc analyses comparing patients initially prescribed 12.5, 25, or 50 mg of chlorthalidone per day with those prescribed 12.5, 25, or 50 mg of hydrochlorothiazide per day, the former were more likely to be hospitalized with hypokalemia for all 6 comparisons in which a statistically significant association was found. The results of other effectiveness and safety outcomes were also consistent with those of the main analysis.

Limitation: Unmeasured differences in baseline characteristics or physician treatment approaches or an insufficiently large sample may have limited the ability to detect small differences in the comparative effectiveness of the drugs.

Conclusion: As typically prescribed, chlorthalidone in older adults was not associated with fewer adverse cardiovascular events or deaths than hydrochlorothiazide. However, it was associated with a greater incidence of electrolyte abnormalities, particularly hypokalemia.

Primary funding source: Ontario Ministry of Health and Long-Term Care.