Chlorthalidone Versus Hydrochlorothiazide for the Treatment of Hypertension in Older Adults: A Population-Based Cohort Study

Study Questions:

How effective and safe are chlorthalidone and hydrochlorothiazide in older adults?


All individuals ages 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 in this study. Each chlorthalidone recipient was matched to up to two hydrochlorothiazide recipients on the basis of age, sex, year of treatment initiation, and propensity score. 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. The investigators used Cox proportional hazards regression to compare outcomes of patients treated with chlorthalidone and those treated with hydrochlorothiazide.


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 [AHR], 0.93; 95% confidence interval [CI], 0.81-1.06). Patients treated with chlorthalidone were more likely to be hospitalized with hypokalemia (AHR, 3.06; 95% CI, 2.04-4.58) or hyponatremia (AHR, 1.68; 95% CI, 1.24-2.28). In nine 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 six 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.


The authors concluded that chlorthalidone in older adults was not associated with fewer adverse cardiovascular events or deaths than hydrochlorothiazide.


This large population-based cohort study of older adults reported no difference between chlorthalidone and hydrochlorothiazide, as typically prescribed, with respect to stroke, myocardial infarction, heart failure, or death. However, patients treated with chlorthalidone were approximately 3 times more likely to be hospitalized with hypokalemia and approximately 1.7 times more likely to be hospitalized with hyponatremia than those prescribed hydrochlorothiazide. In the absence of convincing evidence for the superiority of either chlorthalidone or hydrochlorothiazide, clinicians who care for older adults should focus primarily on reaching patient-relevant blood pressure goals while being mindful of the risk for electrolyte abnormalities in patients treated with diuretics.

Clinical Topics: Prevention, Hypertension

Keywords: Incidence, Myocardial Infarction, Stroke, Hyponatremia, Follow-Up Studies, Hypokalemia, Cardiovascular Diseases, Blood Pressure, Lymphocyte Activation, Blood Pressure Determination, Hypertension

< Back to Listings