FPIN's Help Desk Answers

Chlorthalidone vs. Hydrochlorothiazide for Treatment of Hypertension


Am Fam Physician. 2015 Dec 1;92(11):1015-1016.

Clinical Question

Is chlorthalidone more effective than hydrochlorothiazide for treatment of hypertension?

Evidence-Based Answer

Chlorthalidone produces slightly greater reductions in blood pressure compared with hydrochlorothiazide (HCTZ), but it is associated with greater declines in serum potassium levels. (Strength of Recommendation [SOR]: C, based on a meta-analysis of disease-oriented evidence.) Chlorthalidone lowers the risk of cardiovascular events about 18% more than HCTZ at the same achieved blood pressure. (SOR: B, based on a meta-analysis.)

In 2010, a meta-analysis of 137 randomized controlled trials (RCTs; N = 5,843) examined the effectiveness of chlorthalidone and HCTZ as monotherapy for hypertension.1 A total of 29 trials of chlorthalidone (N = 2,995; dose range = 12.5 to 200 mg, median 25 mg) and 108 trials of HCTZ (N = 2,848; dose range = 3 to 450 mg, median 33 mg) were analyzed based on dose and study duration (all less than one year). When all study durations were pooled, 12.5 to 25 mg of chlorthalidone produced a statistically greater reduction in systolic blood pressure compared with HCTZ (−24 mm Hg vs. −14 mm

Address correspondence to Karyn Springer, MD, at karyn.springer@imail.org. Reprints are not available from the author.

Author disclosure: No relevant financial affiliations.


show all references

1. Ernst ME, Carter BL, Zheng S, Grimm RH Jr. Meta-analysis of dose-response characteristics of hydrochlorothiazide and chlorthalidone: effects on systolic blood pressure and potassium. Am J Hypertens. 2010;23(4):440–446....

2. Roush GC, Holford TR, Guddati AK. Chlorthalidone compared with hydrochlorothiazide in reducing cardiovascular events: systematic review and network meta-analyses. Hypertension. 2012;59(6):1110–1117.

3. Ernst ME, Carter BL, Goerdt CJ, et al. Comparative antihypertensive effects of hydrochlorothiazide and chlorthalidone on ambulatory and office blood pressure. Hypertension. 2006;47(3):352–358.

4. James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8) [published correction appears in JAMA. 2014;311(17):1809]. JAMA. 2014;311(5):507–520.

Help Desk Answers provides answers to questions submitted by practicing family physicians to the Family Physicians Inquiries Network (FPIN). Members of the network select questions based on their relevance to family medicine. Answers are drawn from an approved set of evidence-based resources and undergo peer review.

The complete database of evidence-based questions and answers is copyrighted by FPIN. If interested in submitting questions or writing answers for this series, go to http://www.fpin.org or e-mail: questions@fpin.org.

This series is coordinated by John E. Delzell, Jr., MD, MSPH, Assistant Medical Editor.


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