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Hydra, a Computer-Based Platform for Aiding Clinicians in Cardiovascular Analysis and Diagnosis

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Published on: September 26, 2018

Chlorthalidone vs. Hydrochlorothiazide for Hypertension-Cardiovascular Events.

Areef Ishani¹, William C Cushman¹, Sarah M Leatherman¹

¹From Minneapolis Veterans Affairs (VA) Health Care System, and the Department of Medicine, University of Minnesota - both in Minneapolis (A.I.); Medical Service, Memphis VA Medical Center, and the Department of Preventive Medicine, University of Tennessee Health Science Center - both in Memphis (W.C.C.); the Cooperative Studies Program Coordinating Center, VA Boston Healthcare System (S.M.L., R.A.L., P.W., C.H., A.K., M.T.B., L.D.F., R.E.F.), the Department of Biostatistics, Boston University School of Public Health (S.M.L., R.A.L.), and the Department of Medicine, Boston University School of Medicine (M.T.B., R.E.F.) - all in Boston; Pharmacy Benefits Management Services (P.A.G.) and the Office of Research and Development (G.D.H.), Department of Veterans Affairs, Washington, DC; VA Greater Los Angeles Healthcare System, and the David Geffen School of Medicine, University of California, Los Angeles - both in Los Angeles (P.A.G.); and Michael E. DeBakey VA Medical Center, and the Department of Medicine, Baylor College of Medicine - both in Houston (A.A.T.).

The New England Journal of Medicine

|December 14, 2022

Summary

Chlorthalidone did not show superiority over hydrochlorothiazide in preventing major cardiovascular events in hypertensive patients. Both drugs demonstrated similar efficacy, though chlorthalidone was associated with higher rates of hypokalemia.

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Area of Science:

Cardiology
Pharmacology
Clinical Trials

Background:

The comparative effectiveness of chlorthalidone and hydrochlorothiazide for major adverse cardiovascular events (MACE) in hypertension management remains unclear.
Thiazide diuretics are a cornerstone in hypertension treatment, necessitating clear guidance on optimal agent selection.

Purpose of the Study:

To compare the efficacy of chlorthalidone versus hydrochlorothiazide in preventing MACE in older adults with hypertension.
To assess the safety profiles of chlorthalidone and hydrochlorothiazide in the target patient population.

Main Methods:

A pragmatic randomized trial involving 13,523 adults aged 65+ with hypertension, previously on hydrochlorothiazide.
Participants were randomized to continue hydrochlorothiazide or switch to chlorthalidone at standard doses.
The primary outcome was a composite of cardiovascular events and non-cancer-related death, with safety monitoring.

Main Results:

No significant difference in the primary composite outcome was observed between the chlorthalidone group (10.4%) and the hydrochlorothiazide group (10.0%) after a median follow-up of 2.4 years (HR, 1.04; 95% CI, 0.94-1.16).
Individual components of the primary outcome did not differ significantly between the groups.
The incidence of hypokalemia was significantly higher in the chlorthalidone group (6.0%) compared to the hydrochlorothiazide group (4.4%).

Conclusions:

In this large pragmatic trial, chlorthalidone did not demonstrate superior efficacy over hydrochlorothiazide in reducing major cardiovascular outcomes or non-cancer-related deaths.
The findings suggest that commonly used doses of these thiazide diuretics offer comparable cardiovascular protection, but chlorthalidone is associated with a higher risk of hypokalemia.