Published Online
on November 24, 2003

A more recent version of this article appeared on January 1, 2004

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Submitted on September 12, 2003
Revised on September 30, 2003

Hydrochlorothiazide Versus Chlorthalidone. Evidence Supporting Their Interchangeability

Barry L. Carter^*; Michael E. Ernst; and Jerome D. Cohen

From the Division of Clinical and Administrative Pharmacy, College of Pharmacy, and the Department of Family Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa (B.L.C., M.E.E.), Iowa City, and the Department of Internal Medicine (Cardiology), St Louis University School of Medicine (J.D.C.), St Louis, Mo.

^* To whom correspondence should be addressed. E-mail: barry-carter{at}uiowa.edu.

Abstract--Thiazide diuretics are one of the preferred pharmacologic treatments for hypertension. Hydrochlorothiazide and chlorthalidone have been the 2 most commonly used diuretics in major clinical trials. Treatment guidelines and compendia often consider these 2 drugs interchangeable agents within the class of thiazide or thiazide-like diuretics. Many sources list them as equipotent. Despite these beliefs, there is some suggestion that cardiovascular outcomes are not necessarily the same with these 2 drugs. We conducted a literature search from 1960 to 2003 to identify studies that evaluated the pharmacokinetic and blood pressure-lowering effects of these 2 agents. There are significant pharmacokinetic and pharmacodynamic differences between these diuretics. Chlorthalidone is 1.5 to 2.0 times as potent as hydrochlorothiazide, and the former has a much longer duration of action. Whether these pharmacokinetic and pharmacodynamic features cause differences in outcomes is not known.

Key words: clinical trials • diuretics • antihypertensive therapy • hypertension, detection and control

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