Perspective:

At some point, it may be reasonable to acknowledge that a competition has ended in a draw. Chlorthalidone was approved in 1960 and was a great advance in hypertension management at that time. Its use dramatically decreased in 1977 once hydrochlorothiazide was approved. In recent decades, however, many clinicians felt that chlorthalidone was a superior drug in the treatment of hypertension, and its use enjoyed a substantial rebound. In 2022, the Diuretic Comparison Project showed that subjects taking chlorthalidone did not have superior cardiovascular outcomes compared to patients on hydrochlorothiazide. Now, this prespecified secondary analysis showed no superiority in chlorthalidone preventing renal outcomes.

Much has changed since 1960, and since 1977. Diets, prevalence of many chronic diseases, weight, recognition of social determinants of health, and exercise level are different now when compared to then. But importantly, clinicians are treating individual patients with a wide variety of comorbidities and expectations, including insurance coverage and lifestyles. It is also important to note that the patient cohort in this trial was almost entirely male. There are also “newer” medications that do not introduce the concern of hypokalemia at all and come without the side effect of excess urination, which can affect adherence in this largely asymptomatic disease.

It may be time to call the “competition” between these two “vintage” medications a tie and leave it to the clinician to see which one may work better on an individual patient with their own unique set of comorbidities. While thiazide diuretics may be first-line therapy in many guidelines, other medications may be better first choices for most of our patients. Enough attention has probably been paid to minor differences in these functionally equivalent thiazide diuretics. Clinicians can be confident that either is just fine to try and likely to work well. But watch the potassium!