Abstract
Background
Chlorthalidone is recommended over hydrochlorothiazide (HCTZ) as the preferred thiazide,
but the supporting evidence is not robust at routinely used doses, or in whites vs
blacks, in whom differences in response to thiazides are well known. We compare the
efficacy and safety of HCTZ and chlorthalidone as first-line therapies for white and
black hypertensive patients.
Methods
We compared treatment-related outcomes between the HCTZ arm (12.5 mg for 2-3 weeks;
25 mg for additional 6 weeks) of the Pharmacogenomic Evaluation of Antihypertensive
Responses (PEAR, n = 376) and chlorthalidone arm (15 mg for 2 weeks; 25 mg for additional
6 weeks) of PEAR-2 (n = 326) clinical trials, in 17–65-year-old mild-moderate uncomplicated
hypertensive whites and blacks.
Results
Mean systolic/diastolic blood pressure (SBP/DBP) reduction with HCTZ vs chlorthalidone:
8 ± 8/4 ± 5 vs 12 ± 9/7 ± 5 mm Hg in whites (P < 10−6 SBP and DBP); 12 ± 10/7 ± 6 vs 15 ± 10/9 ± 6 in blacks (P = .008 SBP, P = .054 DBP). Treatment with HCTZ vs chlorthalidone in whites resulted in significantly
fewer patients achieving target BP (<140/90 mm Hg) (44% vs 57%, P = .018) and clinical response rate (≥10 mm Hg DBP reduction); and significantly higher
nonresponse rate (<6 mm Hg DBP reduction); but no significant differences in rates
among blacks (eg, target-BP rate: 56% vs 63%, P = .31). HCTZ treatment led to significantly lower rates of hypokalemia and hyperuricemia
in whites and blacks, vs chlorthalidone, and significantly lower odds of requiring
potassium supplementation among blacks (odds ratio 0.16; 95% confidence interval,
0.07-0.37; P = 3.4e−7).
Conclusion
Compared with HCTZ, chlorthalidone showed greater blood pressure lowering and adverse
metabolic effects in whites, but similar blood pressure lowering and greater adverse
effects in blacks; suggesting that the recent guideline recommendations to choose
chlorthalidone over HCTZ may not be warranted in blacks.
Keywords
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Article Info
Publication History
Published online: January 09, 2021
Footnotes
Funding: The Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) study was supported by the Pharmacogenomics Research Network grant U01-GM074492 and the National Institute of Health National Center for Advancing Translational Sciences under the award number UL1 TR000064 (University of Florida), UL1 TR000454 (Emory University), and UL1 TR000135 (Mayo Clinic). The PEAR study was also supported by funds from the Mayo Foundation. LMSC received the predoctoral fellowship grant 20PRE35210065 from the American Heart Association. The funders/sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. The content is solely the responsibility of the authors and does not represent the official views of the National Institutes of Health or the American Heart Association.
Conflict of Interest: None.
Authorship:All the authors had access to data and a role in writing this manuscript. LMSC: conceptualization, methodology, formal analysis, writing – original draft preparation, visualization, funding acquisition; AC: conceptualization, funding acquisition, writing – review & editing; JG: conceptualization, funding acquisition, writing – review & editing; RC-D: conceptualization, funding acquisition, writing – review & editing; JJ: conceptualization, methodology, funding acquisition, writing – review & editing, supervision. All authors read and approved the final manuscript. The PEAR and PEAR-2 study data are available under dbGaP Accession: phs000649.v2.p2 at https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000649.v2.p2. Any data not available in dbGaP can be obtained through request to the corresponding author.
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