Assessing Chlorthalidone, Hydrochlorothiazide Treatment for Cardiovascular Diseases, with Areef Ishani, MD, MS

Chlorthalidone has shown superiority in previous trials evaluating cardiovascular disease but is less commonly prescribed compared to hydrochlorothiazide, which has dominated the US market. The Diuretic Comparison Project (DCP) study aimed to provide clarity on their comparative efficacy.

In an interview with HCPLive, Areef Ishani, MD, MS, chief of medicine at the Minneapolis VA Health Care System, discusses the results of the DCP, presented at the National Kidney Foundation (NKF) 2024 Spring Clinical Meeting, which compared these drugs for the treatment of cardiovascular diseases.

The main reason researchers believed in chlorthalidone's superiority lies in its long half-life and potential pleiotropic effects, including better 24-hour blood pressure control and the potential inhibition of platelet aggregation.

The study employed a large, pragmatic, randomized controlled trial design, with participants randomized to either chlorthalidone or hydrochlorothiazide, aiming to eliminate confounding factors and provide robust findings. Investigators also used a stratified randomization by site to further account for potential confounding factors.

Contrary to expectations, the study's primary outcomes did not show a significant difference between chlorthalidone and hydrochlorothiazide in major adverse cardiovascular outcomes or non-cancer deaths. Subsequent analyses on renal outcomes also revealed no notable differences between the drugs.

Therefore, findings indicated both drugs can be effectively used to prevent cardiovascular diseases or adverse renal outcomes. Additionally, the results advocate for considering combination therapies, especially for chlorthalidone, as there are fewer combination pills available compared to hydrochlorothiazide, potentially leading to improved adherence and better blood pressure control.

Further research is underway to explore other aspects.

“For kidney stones, a mainstay of therapy historically has been hydrochlorothiazide,” Ishani said. “It has potentially been shown to reduce stones. There was a publication just came out about a year ago called NOSTONE that showed that there was no improvement in stones associated with hydrochlorothiazide.”

This ongoing work aims to deepen the understanding of these medications and optimize treatment strategies for patients.

“Either drug can be used, and I think people should be open to more combination pills,” Ishani emphasized.

Disclosures: Ishani has no disclosures to report.