Chlorthalidone appears to be more effective than hydrochlorothiazide in reducing major adverse cardiovascular events (MACE) in the long term, according to a recent study published in the Journal of Hypertension.

To compare the clinical benefits of these diuretics, the study authors conducted a literature search that reported on outcomes such as MACE and left ventricular mass. Findings from these studies showed mixed results, with the network meta-analysis of randomized trials favoring chlorthalidone for MACE reduction (hazard ratio [HR] 0.79; 95% CI, 0.72-0.88; P <.0001), while 2 observational cohort studies concluded there were no differences between the treatments.

However, the trials that did show superiority of chlorthalidone were found to have longer follow-up periods (4.3-7.0 years); in the observational studies, follow-up was only 0.95 and 0.25 years. “As differences in outcomes for MACE in hypertension trials with various interventions only emerge after prolonged (>1 year) therapy, differences in follow-up explain these discrepant results,” the authors explained.

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Findings also showed that treatment with chlorthalidone significantly reduced left ventricular mass and also led to greater reductions in nighttime blood pressure, oxidative stress, and platelet aggregations; greater improvements in endothelial function were also reported.

Based on the long-term available data, the authors concluded that chlorthalidone appears to be superior to HCTZ with regard to MACE reduction. They added that “The Veterans Administration’s trial in progress may provide definitive answer to these questions.”


Roush, George C; Messerli, Franz H. Chlorthalidone versus hydrochlorothiazide. [published online January 19, 2021]. Publish ahead of print. Journal of Hypertension. doi: 10.1097/HJH.0000000000002771

This article originally appeared on MPR