(HealthDay News) — In real-world practice, chlorthalidone use is not associated with significant cardiovascular benefits versus hydrochlorothiazide, but it is associated with a greater risk for renal and electrolyte abnormalities, according to a study published online in JAMA Internal Medicine.

George Hripcsak, MD, from the Columbia University Irving Medical Center in New York City, and colleagues used data from administrative claims databases and electronic health records (2001 through 2018) to compare the effectiveness and safety of chlorthalidone and hydrochlorothiazide as first-line therapies for hypertension in real-world practice. A composite outcome included acute myocardial infarction, hospitalization for heart failure, ischemic or hemorrhagic stroke, and sudden cardiac death.

The researchers identified 730,225 individuals (mean age, 51.5 years; 61.6% women), of whom 36,918 were dispensed or prescribed chlorthalidone and had 149 composite outcome events, and 693,337 individuals dispensed or prescribed hydrochlorothiazide with 3089 composite outcome events. There were no significant differences in the associated risk for myocardial infarction, hospitalized heart failure, or stroke for chlorthalidone versus hydrochlorothiazide (calibrated hazard ratio [HR] for the composite cardiovascular outcome, 1.00; 95% confidence interval [CI], 0.85 to 1.17). Chlorthalidone was associated with a significantly higher risk for hypokalemia (HR, 2.72; 95% CI, 2.38 to 3.12), hyponatremia (HR, 1.31; 95% CI, 1.16 to 1.47), acute renal failure (HR, 1.37; 95% CI, 1.15 to 1.63), chronic kidney disease (HR, 1.24; 95% CI, 1.09 to 1.42), and type 2 diabetes mellitus (HR, 1.21; 95% CI, 1.12 to 1.30), as well as a lower risk for diagnosed abnormal weight gain (HR, 0.73; 95% CI, 0.61 to 0.86).

“These findings do not support current recommendations to prefer chlorthalidone versus hydrochlorothiazide for hypertension treatment in first-time users,” the authors write.

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Several authors disclosed financial ties to the pharmaceutical industry.


Hripcsak G, Suchard MA, Shea S, et al. Comparison of Cardiovascular and Safety Outcomes of Chlorthalidone vs Hydrochlorothiazide to Treat Hypertension [published online February 17, 2020]. JAMA Intern Med. doi: 10.1001/jamainternmed.2019.7454

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