Chlorthalidone, hydrochlorothiazide comparable in older hypertensive adults

Results from a new study suggest that chlorthalidone and hydrochlorothiazide are associated with similar rates of death and CV hospitalizations. However, older adults prescribed chlorthalidone were three times more likely to be hospitalized for hypokalemia and about 1.7 times more likely to be hospitalized for low sodium than those prescribed hydrochlorothiazide.

The study included 29,873 patients aged 66 years or older who were randomly assigned chlorthalidone (n=10,384) or hydrochlorothiazide (n=19,489).

Irfan A. Dhalla, MD 

Irfan A. Dhalla

The primary outcome — a composite of death or hospitalization for MI, HF or stroke — occurred at a rate of 3.2 events per 100 person-years of follow-up for patients assigned chlorthalidone compared with a rate of 3.4 events per 100 person-years of follow-up for those assigned hydrochlorothiazide (adjusted HR=0.93; 95% CI, 0.81-1.06).

Compared with the hydrochlorothiazide group, patients assigned chlorthalidone were more likely to be hospitalized with hypokalemia (adjusted HR=3.06; 95% CI, 2.04-4.58) and hyponatremia (adjusted HR=1.68; 95% CI, 1.24-2.28), according to data published in Annals of Internal Medicine.

In addition, researchers conducted nine post-hoc analyses that compared patients prescribed 12.5 mg, 25 mg or 50 mg of chlorthalidone per day with patients prescribed 12.5 mg, 25 mg or 50 mg of hydrochlorothiazide per day. Patients prescribed chlorthalidone were more likely to be hospitalized for hypokalemia for all six comparisons in which a significant association was found, according to the abstract. Other effectiveness and safety outcomes were consistent with those reported in the main analysis.

"In the absence of convincing evidence for the superiority of either chlorthalione or hydrochlorothiazide, we believe that clinicians who care for older adults should focus primarily on reaching patient-relevant BP goals while being mindful of the risk for electrolyte abnormalities in patients treated with diuretics," Irfan A. Dhalla, MD, assistant professor at St. Michael's Hospital and Institute for Clinical Evaluative Sciences, Toronto, and colleagues wrote. "A large, well-designed, carefully conducted randomized trial would be necessary to definitively determine the comparative safety and effectiveness of hydrochlorothiazide and chlorthalidone."

For more information:

Dhalla IA. Ann Intern Med. 2013;158:

Disclosure: The researchers report no relevant financial disclosures.

Results from a new study suggest that chlorthalidone and hydrochlorothiazide are associated with similar rates of death and CV hospitalizations. However, older adults prescribed chlorthalidone were three times more likely to be hospitalized for hypokalemia and about 1.7 times more likely to be hospitalized for low sodium than those prescribed hydrochlorothiazide.

The study included 29,873 patients aged 66 years or older who were randomly assigned chlorthalidone (n=10,384) or hydrochlorothiazide (n=19,489).

Irfan A. Dhalla, MD 

Irfan A. Dhalla

The primary outcome — a composite of death or hospitalization for MI, HF or stroke — occurred at a rate of 3.2 events per 100 person-years of follow-up for patients assigned chlorthalidone compared with a rate of 3.4 events per 100 person-years of follow-up for those assigned hydrochlorothiazide (adjusted HR=0.93; 95% CI, 0.81-1.06).

Compared with the hydrochlorothiazide group, patients assigned chlorthalidone were more likely to be hospitalized with hypokalemia (adjusted HR=3.06; 95% CI, 2.04-4.58) and hyponatremia (adjusted HR=1.68; 95% CI, 1.24-2.28), according to data published in Annals of Internal Medicine.

In addition, researchers conducted nine post-hoc analyses that compared patients prescribed 12.5 mg, 25 mg or 50 mg of chlorthalidone per day with patients prescribed 12.5 mg, 25 mg or 50 mg of hydrochlorothiazide per day. Patients prescribed chlorthalidone were more likely to be hospitalized for hypokalemia for all six comparisons in which a significant association was found, according to the abstract. Other effectiveness and safety outcomes were consistent with those reported in the main analysis.

"In the absence of convincing evidence for the superiority of either chlorthalione or hydrochlorothiazide, we believe that clinicians who care for older adults should focus primarily on reaching patient-relevant BP goals while being mindful of the risk for electrolyte abnormalities in patients treated with diuretics," Irfan A. Dhalla, MD, assistant professor at St. Michael's Hospital and Institute for Clinical Evaluative Sciences, Toronto, and colleagues wrote. "A large, well-designed, carefully conducted randomized trial would be necessary to definitively determine the comparative safety and effectiveness of hydrochlorothiazide and chlorthalidone."

For more information:

Dhalla IA. Ann Intern Med. 2013;158:

Disclosure: The researchers report no relevant financial disclosures.