CoChat
Sign Up
Cited by 161Blood Pressure and Hypertension StudiesSodium Intake and HealthHormonal Regulation and Hypertension

Head-to-Head Comparisons of Hydrochlorothiazide With Indapamide and Chlorthalidone: Antihypertensive and Metabolic Effects

Open access
Roush, George C., Ernst, Michael E., Kostis, John B., Tandon, Suraj, Sica, Domenic A.·2015·Hypertension
DOI 10.1161/hypertensionaha.114.05021
Open this paper in CoChat — free accountOpen PDF

Abstract

Hydrochlorothiazide (HCTZ) has often been contrasted with chlorthalidone, but relatively little is known about HCTZ versus indapamide (INDAP). This systematic review retrieved 9765 publications, and from these, it identified 14 randomized trials with 883 patients comparing HCTZ with INDAP and chlorthalidone on antihypertensive potency or metabolic effects. To make fair comparisons, the dose of the diuretic in each arm was assigned 1 of 3 dose levels. In random effects meta-analysis, INDAP and chlorthalidone lowered systolic blood pressure more than HCTZ: −5.1 mm Hg (95% confidence interval, −8.7 to −1.6); P =0.004 and −3.6 mm Hg (95% confidence interval, −7.3 to 0.0); P =0.052, respectively. For both comparisons, there was minimal heterogeneity in effect across trials and no evidence for publication bias. The HCTZ–INDAP contrast was biased in favor of greater HCTZ potency because of a much greater contribution to the overall effect from trials in which the HCTZ arm had a higher dose level than the INDAP arm. For the HCTZ–INDAP comparison, no single trial was responsible for the overall result nor was it possible to detect significant modifications of this comparison by duration of follow-up, high- versus low-bias trials, or the presence or absence of background medications. There were no detectable differences between HCTZ and INDAP in metabolic adverse effects, including effects on serum potassium. In conclusion, these head-to-head comparisons demonstrate that, like chlorthalidone, INDAP is more potent than HCTZ at commonly prescribed doses without evidence for greater adverse metabolic effects.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1161/hypertensionaha.114.05021

Cites

2 of 2 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • 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 [78]

    The Perspectives table (page not specified) reports low potassium and low sodium among adverse metabolic effects, supporting the electrolyte-abnormalities portion. The Discussion (page not specified) reports potassium declines with indapamide and hydrochlorothiazide but says their effects were similar. Neither passage establishes that diuretics precipitate acute kidney injury or that the hypokalemic response is diminished at low eGFR and depends on diuretic type. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 37

  1. 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). JAMA. 2014;311:507-520. doi: 10.1001/jama.2013.284427. · DOI · Paper page
  2. Calhoun DA, Jones D, Textor S, Goff DC, Murphy TP, Toto RD, White A, Cushman WC, White W, Sica D, Ferdinand K, Giles TD, Falkner B, Carey RM; American Heart Association Professional Education Committee. Resistant hypertension: diagnosis, evaluation, and treatment: a scientific statement from the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research. Circulation. 2008;117:e510-e526. doi: 10.1161/CIRCULATIONAHA.108.189141. · DOI
  3. Sica DA. Chapter 130. Thiazide and loop diuretics. In: Izzo Jr, JL, Black HR, Sica DA, eds. Hypertension Primer. Dallas, TX: American Heart Association; 2008:441.
  4. Roush GC, Buddharaju V, Ernst ME. Is chlorthalidone better than hydro- chlorothiazide in reducing cardiovascular events in hypertensives? Curr Opin Cardiol. 2013;28:426-432. doi: 10.1097/HCO.0b013e3283622075. · DOI
  5. Moher D, Liberati A, Tetzlaff J, Altman DG; PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med. 2009;151:264-269, W64.
  6. Bhigjee AI, Seedat YK, Hoosen S, Neerahoo RM, Naidoo K. Biochemical changes in black and Indian hypertensive patients on diuretic therapy. S Afr Med J. 1983;64:969-972.
  7. Elliott WJ, Weber RR, Murphy MB. A double-blind, randomized, pla- cebo-controlled comparison of the metabolic effects of low-dose hydro- chlorothiazide and indapamide. J Clin Pharmacol. 1991;31:751-757.
  8. Emeriau JP, Knauf H, Pujadas JO, Calvo-Gomez C, Abate G, Leonetti G, Chastang C; European Study Investigators. A comparison of indapamide SR 1.5 mg with both amlodipine 5 mg and hydrochlorothiazide 25 mg in elderly hypertensive patients: a randomized double-blind controlled study. J Hypertens. 2001;19:343-350.
  9. Kreeft JH, Langlois S, Ogilvie RI. Comparative trial of indapamide and hydrochlorothiazide in essential hypertension, with forearm plethysmog- raphy. J Cardiovasc Pharmacol. 1984;6:622-626.
  10. Krum H, Skiba M, Gilbert RE. Comparative metabolic effects of hydro- chlorothiazide and indapamide in hypertensive diabetic patients receiving ACE inhibitor therapy. Diabet Med. 2003;20:708-712.
  11. Madkour H, Gadallah M, Riveline B, Plante GE, Massry SG. Comparison between the effects of indapamide and hydrochlorothiazide on creatinine clearance in patients with impaired renal function and hypertension. Am J Nephrol. 1995;15:251-255.
  12. Malini PL, Strocchi EN, Ricci CM, Ambrosinioni E. Indapamide or hydro- chlorothiazide in hypertensive patients resistant to treatment with an angio- tensin-converting enzyme inhibitor. Curr Therap Res. 1994;55:932-937.
  13. Plante GE, Robillard C. Indapamide in the treatment of essential arte- rial hypertension: results of a controlled study. Curr Med Res Opinion. 1983;8:59-66.
  14. Radevski IV, Valtchanova ZP, Candy GP, Wald AM, Ngcezula T, Sareli P. Comparison of indapamide and low-dose hydrochlorothiazide mono- therapy in black patients with mild to moderate hypertension. S Afr Med J. 2002;92:532-536.
  15. Spence JD, Huff M, Barnett PA. Effects of indapamide versus hydrochlo- rothiazide on plasma lipids and lipoproteins in hypertensive patients: a direct comparison. Can J Clin Pharmacol. 2000;7:32-37.
  16. Ernst ME, Carter BL, Goerdt CJ, Steffensmeier JJ, Phillips BB, Zimmerman MB, Bergus GR. Comparative antihypertensive effects of hydrochlorothiazide and chlorthalidone on ambulatory and office blood pressure. Hypertension. 2006;47:352-358. doi: 10.1161/01. HYP.0000203309.07140.d3. · DOI · Paper page
  17. Kwon BJ, Jang SW, Choi KY, Kim DB, Cho EJ, Ihm SH, Youn HJ, Kim JH. Comparison of the efficacy between hydrochlorothiazide and chlorthalidone on central aortic pressure when added on to candesartan in treatment-naive patients of hypertension. Hypertens Res. 2013;36:79-84. doi: 10.1038/hr.2012.143. · DOI
  18. Pareek A, Basavanagowdappa H, Zawar S, Kumar A, Chandurkar N. A randomized, comparative study evaluating the efficacy and tolerability of losartan-low dose chlorthalidone (6.25 mg) combination with losar- tan-hydrochlorothiazide (12.5 mg) combination in Indian patients with mild-to-moderate essential hypertension. Expert Opin Pharmacother. 2009;10:1529-1536. doi: 10.1517/14656560902991514. · DOI
  19. Peterzan MA, Hardy R, Chaturvedi N, Hughes AD. Meta-analysis of dose- response relationships for hydrochlorothiazide, chlorthalidone, and bendro- flumethiazide on blood pressure, serum potassium, and urate. Hypertension. 2012;59:1104-1109. doi: 10.1161/HYPERTENSIONAHA.111.190637. · DOI
  20. 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;23:440-446. doi: 10.1038/ajh.2010.1. · DOI
  21. Gosse P, Sheridan DJ, Zannad F, Dubourg O, Guéret P, Karpov Y, de Leeuw PW, Palma-Gamiz JL, Pessina A, Motz W, Degaute JP, Chastang C. Regression of left ventricular hypertrophy in hypertensive patients treated with indapamide SR 1.5 mg versus enalapril 20 mg: the LIVE study. J Hypertens. 2000;18:1465-1475.
  22. Donnelly R, Molyneaux LM, Willey KA, Yue DK. Comparative effects of indapamide and captopril on blood pressure and albumin excretion rate in diabetic microalbuminuria. Am J Cardiol. 1996;77:26B-30B.
  23. Hallab M, Gallois Y, Chatellier G, Rohmer V, Fressinaud P, Marre M. Comparison of reduction in microalbuminuria by enalapril and hydro- chlorothiazide in normotensive patients with insulin dependent diabetes. BMJ. 1993;306:175-182.
  24. Vergely C, Walker MK, Zeller M, Rademakers JR, Maupoil V, Schiavi P, Guez D, Rochette L. Antioxidant properties of indapamide, 5-OH indapamide and hydrochlorothiazide evaluated by oxygen-radical absorbing capacity and elec- tron paramagnetic resonance. Mol Cell Biochem. 1998;178:151-155.
  25. PROGRESS Collaborative Group. Randomised trial of a perindopril- based blood-pressure-lowering regimen among 6105 individuals with pre- vious stroke or transient ischaemic attack. Lancet. 2001;358:1033-1041.
  26. Chalmers J, Arima H, Woodward M, Mancia G, Poulter N, Hirakawa Y, Zoungas S, Patel A, Williams B, Harrap S. Effects of combination of perindo- pril, indapamide, and calcium channel blockers in patients with type 2 diabetes mellitus: results from the Action In Diabetes and Vascular Disease: Preterax and Diamicron Controlled Evaluation (ADVANCE) trial. Hypertension. 2014;63:259-264. doi: 10.1161/HYPERTENSIONAHA.113.02252. · DOI
  27. Beckett NS, Peters R, Fletcher AE, et al; HYVET Study Group. Treatment of hypertension in patients 80 years of age or older. N Engl J Med. 2008;358:1887-1898. doi: 10.1056/NEJMoa0801369. · DOI · Paper page
  28. Sassard J, Bataillard A, McIntyre H. An overview of the pharmacol- ogy and clinical efficacy of indapamide sustained release. Fundam Clin Pharmacol. 2005;19:637-645. doi: 10.1111/j.1472-8206.2005.00377.x. · DOI
  29. Roush GC, Fagard RH, Salles GF, Pierdomenico SD, Reboldi G, Verdecchia P, Eguchi K, Kario K, Hoshide S, Polonia J, de la Sierra A, Hermida RC, Dolan E, Zamalloa H; ABC-H Investigators. Prognostic impact from clinic, daytime, and nighttime systolic blood pres- sure in 9 cohorts of 13 844 patients with hypertension. J Hypertens. 2014;32:2332-2340.
  30. Roush GC, Fapohunda J, Kostis JB. Evening dosing of antihypertensive therapy to reduce cardiovascular events: a third type of evidence based on a systematic review and meta-analysis of randomized trials. J Clin Hypertens (Greenwich). 2014;16:561-568. doi: 10.1111/jch.12354. · DOI
  31. Hermida RC, Ayala DE, Mojón A, Fernández JR. Influence of circa- dian time of hypertension treatment on cardiovascular risk: results of the MAPEC study. Chronobiol Int. 2010;27:1629-1651. doi: 10.3109/07420528.2010.510230. · DOI · Paper page
  32. Ambrosioni E, Safar M, Degaute JP, Malin PL, MacMahon M, Pujol DR, de Cordoüe A, Guez D. Low-dose antihypertensive therapy with 1.5 mg sustained-release indapamide: results of randomised double-blind controlled studies. European study group. J Hypertens. 1998;16:1677-1684.
  33. Thomas JR. A review of 10 years of experience with indapamide as an antihypertensive agent. Hypertension. 1985;7(suppl II):152-156.
  34. Aubert I, Djian F, Rouffy J. Beneficial effects of indapamide on lipopro- teins and apoproteins in ambulatory hypertensive patients. Am J Cardiol. 1990;65:77H-80H.
  35. Campbell DB. The possible mode of action of indapamide: a review. Curr Med Res Opin. 1983;8(suppl 3):9-24.
  36. Witchitz S, Kamoun A, Chiche P. A double-blind study in hypertensive patients of an original new compound, indapamide. Curr Med Res Opin. 1975;3:1-8. doi: 10.1185/03007997509113637. · DOI
  37. IMS Institute for Healthcare Informatics. Medicine Use and Shifting Costs of Healthcare: A Review of the Use of Medicines in the United States in 2013. Appendix 3. Parsippany, NJ: IMS Institute for Healthcare Informatics. 2014.

Cited by

Sorted by citations

Authors
Roush, G. C., Ernst, M. E., Kostis, J. B., Tandon, S., & Sica, D. A.
Affiliations
University of Iowa (US)
ORCID
Venue
Hypertension
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2015-05
Volume
65
Issue
5
Pages
1041-1046
ISSN
  • 0194-911X (ISSN-L)
  • 1524-4563
DOI
10.1161/hypertensionaha.114.05021
OpenAlex
W2140854783
Cited by
161
References
2
Citations by year
2026: 8 · 2025: 9 · 2024: 13 · 2023: 14 · 2022: 15 · 2021: 11 · 2020: 15 · 2019: 20 · 2018: 16 · 2017: 18 · 2016: 15 · 2015: 5 · 2014: 1
FWCI
13.10
Type
journal article
Language
en
Open access
Locations
  • Hypertension (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
  • Health Sciences › Nursing › Nutrition and Dietetics › Sodium Intake and Health
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
Keywords
hydrochlorothiazide, indapamide, chlorthalidone, thiazide-like diuretics, systolic blood pressure reduction, serum potassium, metabolic side effects, dose comparison, antihypertensive therapy
MeSH terms
Blood Pressure, Chlorthalidone, Diuretics, Humans, Hydrochlorothiazide, Hypertension, Hypokalemia, Indapamide, Potassium, Treatment Outcome

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 ›

Are you an author, or do you see a problem with this page? Request a review