Published Online
on January 23, 2006

A more recent version of this article appeared on March 1, 2006

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Submitted on September 14, 2005
Revised on October 3, 2005

Comparative Antihypertensive Effects of Hydrochlorothiazide and Chlorthalidone on Ambulatory and Office Blood Pressure

Michael E. Ernst^*; Barry L. Carter; Chris J. Goerdt; Jennifer J.G. Steffensmeier; Beth Bryles Phillips; M. Bridget Zimmerman; and George R. Bergus

From the Division of Clinical and Administrative Pharmacy, College of Pharmacy (M.E.E., B.L.C., J.J.G.S., B.B.P.), Departments of Family Medicine (M.E.E., B.L.C., G.R.B.) and Internal Medicine (C.J.G.), Roy J. and Lucille A. Carver College of Medicine, and Department of Biostatistics, College of Public Health (M.B.Z.), University of Iowa; Pharmacy Department (J.J.G.S.), Veterans Affairs Medical Center; and Department of Pharmaceutical Care (B.B.P.), University of Iowa Hospitals and Clinics, Iowa City, Iowa.

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

Abstract--Low-dose thiazide-type diuretics are recommended as initial therapy for most hypertensive patients. Chlorthalidone has significantly reduced stroke and cardiovascular end points in several landmark trials; however, hydrochlorothiazide remains favored in practice. Most clinicians assume that the drugs are interchangeable, but their antihypertensive effects at lower doses have not been directly compared. We conducted a randomized, single-blinded, 8-week active treatment, crossover study comparing chlorthalidone 12.5 mg/day (force-titrated to 25 mg/day) and hydrochlorothiazide 25 mg/day (force-titrated to 50 mg/day) in untreated hypertensive patients. The main outcome, 24-hour ambulatory blood pressure (BP) monitoring, was assessed at baseline and week 8, along with standard office BP readings every 2 weeks. Thirty patients completed the first active treatment period, whereas 24 patients completed both. An order-drug-time interaction was observed with chlorthalidone; therefore, data from only the first active treatment period was considered. Week 8 ambulatory BPs indicated a greater reduction from baseline in systolic BP with chlorthalidone 25 mg/day compared with hydrochlorothiazide 50 mg/day (24-hour mean = -12.4±1.8 mm Hg versus -7.4±1.7 mm Hg; P=0.054; nighttime mean = -13.5±1.9 mm Hg versus -6.4±1.8 mm Hg; P=0.009). Office systolic BP reduction was lower at week 2 for chlorthalidone 12.5 mg/day versus hydrochlorothiazide 25 mg/day (-15.7±2.2 mm Hg versus -4.5±2.1 mm Hg; P=0.001); however, by week 8, reductions were statistically similar (-17.1±3.7 versus -10.8±3.5; P=0.84). Within recommended doses, chlorthalidone is more effective in lowering systolic BPs than hydrochlorothiazide, as evidenced by 24-hour ambulatory BPs. These differences were not apparent with office BP measurements.

Key words: diuretics • blood pressure monitoring, ambulatory • antihypertensive agents • hypertension, essential • antihypertensive therapy

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Chlorthalidone: Has It Always Been the Best Thiazide-Type Diuretic?

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