Same Benefit with Equivalent Doses of Chlorthalidone and HCTZ


Am Fam Physician. 2013 Oct 15;88(8):online.

Clinical Question

Is chlorthalidone safer or more effective than hydrochlorothiazide (HCTZ) in older adults with hypertension?

Bottom Line

In this retrospective analysis, chlorthalidone and HCTZ produced the same clinical outcomes in older adults. In general, chlorthalidone was more likely to be associated with hospitalization for hypokalemia and hyponatremia. When comparing equivalent doses, though, the rates of these adverse effects were the same. If prescribing chlorthalidone, remember that it is 1.5 to 2 times as potent as HCTZ, with a longer duration of action. Use 12.5 mg as a starting dose. (Level of Evidence = 2b)


Using an administrative database, these Canadian researchers enrolled all patients older than 65 years who were newly treated with chlorthalidone or HCTZ. Because this was a retrospective analysis, they could match each patient who was given chlorthalidone with up to two patients who were given HCTZ on the basis of age, sex, year of treatment initiation, and a “propensity score” used to balance additional factors that could signal additional risk. They included a total of 29,873 patients who were followed for up to five years. The rates of the composite outcome of death or hospitalization for heart failure, stroke, or myocardial infarction were low and similar in both groups: 3.2 to 3.4 events per 100 persons per year of follow-up. However, patients treated with chlorthalidone were more likely to be hospitalized for hypokalemia (hazard ratio = 3.06) or hyponatremia (hazard ratio = 1.68). Neither hypokalemia nor hyponatremia was more common when comparing pharmacokinetically equivalent low doses (e.g., 12.5 mg chlorthalidone vs. 25 mg HCTZ), though the difference was present when the same doses were compared. The results are a little muddied because of the nature of this type of study; despite careful matching, there were differences between the two cohorts in terms of other treatments received for hypertension, which is much less likely to occur in large randomized studies.

Study Information

Study design: Cohort (retrospective)

Funding source: Government

Setting: Population-based

Reference: Dhalla IA, Gomes T, Yao Z, et al. Chlorthalidone versus hydrochlorothiazide for the treatment of hypertension in older adults: a population-based cohort study. Ann Intern Med. 2013; 158( 6): 447– 455.



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