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Comment & Response
June 22, 2020

Chlorthalidone and Hydrochlorothiazide for Treatment of Patients With Hypertension

Author Affiliations
  • 1Swiss Cardiovascular Center, University of Bern, Bern, Switzerland
  • 2New York University School of Medicine, New York
  • 3Division of Cardiovascular Disease, University of Alabama at Birmingham
JAMA Intern Med. Published online June 22, 2020. doi:10.1001/jamainternmed.2020.1742

To the Editor In their retrospective observational cohort study, Hripcsak et al1 reported similar efficacy of chlorthalidone (CTD) and hydrochlorothiazide (HCTZ) in the treatment of patients with hypertension but distinct differences in safety, favoring HCTZ. The authors correctly observed that “Outcomes may differ in timing: electrolyte imbalances may occur quickly while cardiovascular outcomes may take longer to occur.”1 In their study, “longer” actually meant a minuscule 0.25 years (92 days). This was the median time of follow-up in the author’s main analysis in their largest database. In post hoc analysis, with shifting to a longer follow-up, the median time was only 0.7 years (267 days). In the landmark Systolic Hypertension in the Elderly Program (SHEP; NCT00000514), Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT; NCT00000542), and Systolic Blood Pressure Intervention Trial (SPRINT; NCT01206062) trials, cardiovascular disease outcome curves only started to diverge after 6 to 12 months. The extremely abbreviated follow-up period in the study of Hripcsak et al1 biases toward 0 any inherent between-group differences in preventing cardiovascular events. Little surprise that cardiovascular outcomes were similar with CTD and HCTZ. This finding, in fact, could have been predicted with high confidence even before these retrospective observational data were analyzed. In contrast, in an observational study by Dorsch et al2 of a cohort of 12 866 men, ranging from 35 to 57 years of age, the median follow-up time was 6 years and the advantage of CTD over HCTZ was 0.79 (0.68, 0.92),2 a point estimate identical to that found in the network meta-analysis of randomized trials of Roush et al,3 0.79 (0.72, 0.88).

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