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Am Fam Physician. 2023;108(3):online

Clinical Question

Is chlorthalidone or hydrochlorothiazide (HCTZ) associated with a difference in the rate of major adverse cardiovascular events when used to treat hypertension?

Bottom Line

There is no difference in cardiovascular outcomes when HCTZ is compared with chlorthalidone. There is a slightly higher risk of hypokalemia with chlorthalidone. (Level of Evidence = 1b)


There has been mixed evidence that chlorthalidone may do a better job at reducing cardiovascular events than HCTZ. Chlorthalidone has been associated with a higher likelihood of adverse events. The pragmatic trial used the U.S. Department of Veterans Affairs electronic health records to identify eligible patients 65 years and older who were currently taking HCTZ at a dosage of 25 or 50 mg daily. If participation was approved by their primary care physician, patients were randomized to continue taking HCTZ or switch to chlorthalidone. Patients in the HCTZ group continued their usual dose, and those randomized to receive chlorthalidone received a dose at one-half of their usual HCTZ dose (e.g., if they usually took 25 mg of HCTZ, they received 12.5 mg of chlorthalidone). Most patients in the HCTZ group were taking 25 mg. This was an open-label trial, although outcome assessors were masked for some outcomes. At baseline, the mean age of the 13,523 participants was 72 years, 97% were men, 15% were Black, and 44% had comorbid type 2 diabetes mellitus.

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POEMs (patient-oriented evidence that matters) are provided by Essential Evidence Plus, a point-of-care clinical decision support system published by Wiley-Blackwell. For more information, see Copyright Wiley-Blackwell. Used with permission.

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