Diuretics for Hypertension: A Review and Update
Abstract
This review and update focuses on the clinical features of hydrochlorothiazide (HCTZ), the thiazide-like agents chlorthalidone (CTDN) and indapamide (INDAP), potassium-sparing ENaC inhibitors and aldosterone receptor antagonists, and loop diuretics. Diuretics are the second most commonly prescribed class of antihypertensive medication, and thiazide-related diuretics have increased at a rate greater than that of antihypertensive medications as a whole. The latest hypertension guidelines have underscored the importance of diuretics for all patients, but particularly for those with salt-sensitive and resistant hypertension. HCTZ is 4.2-6.2 systolic mm Hg less potent than CTDN, angiotensin-converting enzyme inhibitors, beta blockers, and calcium channel blockers by 24-hour measurements and 5.1mm Hg systolic less potent than INDAP by office measurements. For reducing cardiovascular events (CVEs), HCTZ is less effective than enalapril and amlodipine in randomized trials, and, in network analysis of trials, it is less effective than CTDN and HCTZ-amiloride. Combined with thiazide-type diuretics, potassium-sparing agents decrease ventricular ectopy and reduce the risk for sudden cardiac death relative to thiazide-type diuretics used alone. A recent synthesis of 44 trials has shown that the relative potencies in milligrams among spironolactone (SPIR), amiloride, and eplerenone (EPLER) are approximately from 25 to 10 to 100, respectively, which may be important when SPIR is poorly tolerated. SPIR reduces proteinuria beyond that provided by other renin angiotensin aldosterone inhibitors. EPLER also reduces proteinuria and has beneficial effects on endothelial function. While guidelines often do not differentiate among specific diuretics, this review demonstrates that these distinctions are important for managing hypertension.
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Diuretics can precipitate acute kidney injury and electrolyte abnormalities, and the hypokalemic response to diuretics is diminished with low eGFR and depends on the type of diuretic used.
“Diuretics can precipitate acute kidney injury (AKI) and electrolyte abnormalities, and the hypokalemic response to diuretics is diminished with low eGFR and depends on the type of diuretic used.”
From KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (2022) · cites this paper as [79]
The diuretics with the greatest evidence base for reducing cardiovascular outcomes are the thiazide-like diuretics chlorthalidone and indapamide.
“The diuretics with the greatest evidence base for reducing cardiovascular outcomes are the thiazide-like diuretics chlorthalidone and indapamide.368,369”
From Resistant Hypertension: Detection, Evaluation, and Management: A Scientific Statement From the American Heart Association (2018) · cites this paper as [368]
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- Authors
- Roush, G. C., & Sica, D. A.
- Affiliations
- University of Connecticut (US)
- Virginia Commonwealth University (US)
- ORCID
- Roush, George C.
- Venue
- American Journal of Hypertension
- Publisher
- Oxford University Press (OUP)
- Published
- 2016-04-05
- Volume
- 29
- Issue
- 10
- Pages
- 1130-1137
- ISSN
- 0895-7061 (ISSN-L)
- 1941-7225
- OpenAlex
- W2333797217
- Cited by
- 142
- References
- 79
- Citations by year
- 2026: 6 · 2025: 5 · 2024: 17 · 2023: 11 · 2022: 12 · 2021: 13 · 2020: 22 · 2019: 17 · 2018: 15 · 2017: 15 · 2016: 8
- FWCI
- 3.20
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Hypertension (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
- Health Sciences › Nursing › Nutrition and Dietetics › Sodium Intake and Health
- Keywords
- diuretics, hypertension, hydrochlorothiazide, chlorthalidone, indapamide, potassium-sparing agents, mineralocorticoid receptor antagonists, spironolactone, amiloride, eplerenone, loop diuretics, cardiovascular events, sudden cardiac death, ventricular ectopy, proteinuria, endothelial function, salt-sensitive hypertension, resistant hypertension, renin-angiotensin-aldosterone system inhibitors
- MeSH terms
- Diuretics, Humans, Hypertension
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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