Chlorthalidone and Hydrochlorothiazide Offer Similar Kidney benefits in patients with Hypertension: JAMA

The findings, published in JAMA Network Open, revealed that chlorthalidone was not superior to hydrochlorothiazide in improving kidney outcomes but was linked to a higher risk of hypokalemia. The findings suggest similar effectiveness for both medications in managing hypertension and protecting kidney health. Hypokalemia can lead to serious health issues, including arrhythmias and muscle weakness, highlighting a key safety consideration when choosing between these two agents.

Hypertension is a known risk factor for the onset and progression of chronic kidney disease (CKD). However, it remains uncertain whether different thiazide diuretics affect kidney outcomes differently. With this in mind, Areef Ishani, Minneapolis Veterans Affairs (VA) Healthcare System, Minneapolis, Minnesota, and colleagues aimed to compare kidney outcomes in hypertensive patients taking chlorthalidone versus hydrochlorothiazide.

For this purpose, the researchers conducted a secondary analysis of the Diuretic Comparison Project, a randomized clinical trial comparing chlorthalidone and hydrochlorothiazide for hypertension treatment. The study took place between June 1, 2016, and June 1, 2022, across Veterans Affairs facilities nationwide, with follow-up extended to December 31, 2023. The trial included veterans aged 65 and older with hypertension who were taking hydrochlorothiazide. 13,523 participants were randomized to continue hydrochlorothiazide or switch to chlorthalidone.

The main kidney outcome was chronic kidney disease progression, defined by a significant increase in serum creatinine, an eGFR below 15 mL/min, or initiation of dialysis.

Key Findings:

• The analysis included 12,265 participants (90.7%) with at least one baseline and follow-up creatinine measurement, with a median age of 71 years; 3.2% were female, and 96.8% were male. The mean study duration was 3.9 years.
• Chlorthalidone was not superior to hydrochlorothiazide in preventing kidney outcomes (6.0% versus 6.4%; HR = 0.94).
• There were similar results when a 40% or greater reduction in eGFR or other components of the composite outcome were analyzed.
• There was no significant difference in the incidence of chronic kidney disease (21.3% for chlorthalidone versus 20.8% for hydrochlorothiazide).
• Acute kidney injury requiring hospitalization occurred at similar rates in both groups (6.4% for chlorthalidone versus 6.2% for hydrochlorothiazide).
• Chlorthalidone had a significantly higher incidence of hypokalemia compared to hydrochlorothiazide (8.9% versus 6.9%).

The overall findings from the secondary analysis of the DCP indicate that chlorthalidone was not superior to hydrochlorothiazide in improving kidney outcomes at the observed doses. However, there was a slightly higher incidence of hypokalemia in patients randomized to chlorthalidone compared to those on hydrochlorothiazide, even among individuals with CKD, though the difference between the groups was minimal.

"Based on these results, clinicians can confidently use either medication for managing hypertension," the researchers wrote.

Reference:

Ishani A, Hau C, Raju S, et al. Chlorthalidone vs Hydrochlorothiazide and Kidney Outcomes in Patients With Hypertension: A Secondary Analysis of a Randomized Clinical Trial. JAMA Netw Open. 2024;7(12):e2449576. doi:10.1001/jamanetworkopen.2024.49576