New Study Challenges Antihypertensive Guidance

Although current recommendations favor chlorthalidone for the treatment of hypertension, no trials have directly compared its risks and benefits with other thiazide diuretics, according to the researchers.

To compare the safety and effectiveness of chlorthalidone and hydrochlorothiazide as first-line treatment options for hypertension, the researchers conducted an observational comparative cohort study involving 730,225 individuals who were first-time users of antihypertensive monotherapy. Of the 730 225 individuals, 36 918 were taking chlorthalidone and 693 337 were taking hydrochlorothiazide.

The primary outcomes of the study were acute myocardial infarction, hospitalization for heart failure, ischemic or hemorrhagic stroke, and a composite including the first 3 outcomes and sudden cardiac death.

Overall, 149 composite outcome events occurred in those patients taking chlorthalidone and 3089 occurred in those taking hydrochlorothiazide. The researchers observed no significant difference in the risk of myocardial infarction, hospitalized heart failure, or stroke.

However, chlorthalidone was associated with a significantly higher risk of hypokalemia (hazard ratio [HR], 2.72; 95% CI, 2.38-3.12), hyponatremia (HR 1.31; 95% CI, 1.16-1.47), acute renal failure (HR 1.37; 95% CI, 1.15-1.63), chronic kidney disease (HR 1.24; 95% CI, 1.09-1.42), and type 2 diabetes mellitus (HR 1.21; 95% CI, 1.12-1.30).

“Our findings based on currently available data and the most recent advances in observational research do not support the use of chlorthalidone over hydrochlorothiazide. This study found that chlorthalidone use was not associated with significant cardiovascular benefits when compared with hydrochlorothiazide, while its use was associated with greater risk of renal and electrolyte abnormalities. We acknowledge the possibility of residual confounding despite our analytic approach and diagnostics and look forward to the results of the ongoing randomized clinical trial,” the researchers concluded.

—Michael Potts

Reference:
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.