Physician-authored summaries and commentary on the most important medical research, provided by the NEJM Group, a division of the Massachusetts Medical Society.
© Massachusetts Medical SocietyApril 2025
In a secondary analysis from a randomised trial, no important differences were noted.
The Diuretic Comparison Project – a randomised trial in which nearly 14,000 older patients (age, 65 years and older) with hypertension received hydrochlorothiazide (HCTZ) or chlorthalidone – showed no difference between groups in adverse cardiovascular outcomes (NEJM JW Gen Med Jan 15 2023 and N Engl J Med 2022; 387: 2401-2410). In this secondary analysis, the researchers examined renal endpoints, motivated in part by several recent observational studies that suggested slightly worse renal outcomes with chlorthalidone compared with HCTZ (NEJM JW Gen Med Mar 15 2020 and JAMA Intern Med 2020; 180: 542-551; and JAMA Network Open 2021; 4: e2123365).
At baseline, mean estimated glomerular filtration rate (eGFR) was 71mL/min/1.73m2; threequarters of patients had eGFR 60mL/minute or higher, and nearly all the others had stage three chronic kidney disease. During four years of follow up, there were no differences between groups in any of several renal outcomes (i.e. doubling of baseline serum creatinine, 40% or more decrease in eGFR, eGFR below 15mL/min, dialysis initiation or development of incident chronic kidney disease). Serum potassium levels of 3.0mEq/L or lower occurred slightly, but significantly, more commonly with chlorthalidone than with HCTZ (6.5% vs 4.8%).
Comment: The original report from this study and this additional analysis suggest no important differences between HCTZ and chlorthalidone for important clinical outcomes in patients with hypertension. The authors’ conclusion is reasonable: ‘Given these findings, clinicians should feel more confident in using either agent for the treatment of hypertension.’
Allan S. Brett, MD, Clinical Professor of Medicine, University of Colorado School of Medicine, Aurora, USA.
Ishwwani A, et al. Chlorthalidone vs hydrochlorothiazide and kidney outcomes in patients with hypertension: a secondary analysis of a randomized clinical trial. JAMA Netw Open 2024 Dec 10; 7: e2449576.
This summary is taken from the following Journal Watch titles: General Medicine, Ambulatory Medicine, Cardiology, Neurology, Hospital Medicine.