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Thiazide and Thiazide-like Diuretics in the Treatment of Arterial Hypertension: are there Any Differences?

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In the current clinical guidelines for arterial hypertension, diuretics are considered one of the first line antihypertensive drugs, which are equivalent in their effectiveness to other main pharmacological classes used in the treatment of this disease. To date, much attention is paid to both the antihypertensive potential of diuretics and their safety profile and ability to influence prognosis. In this regard, a rational approach to the consideration of the clinical and pharmacological properties of these drugs is the isolation of thiazide and thiazide-like drugs among them, which is reflected in international clinical guidelines. Among thiazide-like diuretics, indapamide occupies a special place, favorably distinguished by its antihypertensive properties, metabolic neutrality, as well as the ability to improve the prognosis and favorably influence hard endpoints in the form of mortality rates in patients with hypertension. A unique feature of indapamide is also the presence, in addition to the direct diuretic effect, pleiotropic properties, including, in particular, some antagonism towards calcium and beneficial effects on arteries. This drug has been studied in a large number of studies, including such "difficult" categories of patients as the elderly and patients with diabetes mellitus, where indapamide has proven its powerful target-organ protective potential and metabolic neutrality, distinguishing it among both thiazide-like and thiazide diuretics. Indapamide provides a comprehensive target-organ protection at the level of the heart, blood vessels, kidneys and brain. Based on this, it can be expected that the widespread use of this drug as part of a first-line combination antihypertensive therapy will not only achieve target blood pressure levet in most patients with hypertension, but also provide an improved prognosis and improve the quality and duration of their life.

About the Author

A. I. Kochetkov
Russian Medical Academy of Continuing Professional Education
Russian Federation

Alexey I. Kochetkov - MD, PhD, Associate Professor, Chair of Therapy and Polymorbid Pathology, Russian Medical Academy of Continuous Professional Education.
Barrikadnaya ul. 2/1-1, Moscow, 125993.


1. Tamargo J., Segura J., Ruilope L.M. Diuretics in the treatment of hypertension. Part 1: thiazide and thiazide-like diuretics. Expert Opin Pharmacother. 2014;15(4):527-47. DOI:10.1517/14656566.2014.879118

2. Williams B., Mancia G., Spiering W., et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension. Eur Heart J. 2018;39(33):3021-3104. DOI:10.1093/eurheartj/ehy339.

3. Рубрикатор клинических рекомендаций Минздрава Российской федерации: клинические рекомендации «Артериальная гипертензия у взрослых» [цитировано 23.11.2020. Доступно на:!/recomend/687].

4. Thomopoulos C., Parati G., Zanchetti A. Effects of blood pressure lowering on outcome incidence in hypertension. 1. Overview, meta-analyses, and meta-regression analyses of randomized trials. J Hypertens. 2014;32(12):2285-95. DOI:10.1097/HJH.0000000000000378.

5. Elliott W.J., Meyer P.M. Incident diabetes in clinical trials of antihypertensive drugs: a network metaanalysis. Lancet. 2007;369(9557):201-7. DOI:10.1016/S0140-6736(07)60108-1.

6. Zhang X., Zhao Q. Association of Thiazide-Type Diuretics With Glycemic Changes in Hypertensive Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Clinical Trials. J Clin Hypertens (Greenwich). 2016;18(4):342-51. DOI:10.1111/jch.12679.

7. Lin J.J., Chang H.C., Ku C.T., Chen H.Y. Hydrochlorothiazide hypertension treatment induced metabolic effects in type 2 diabetes: a meta-analysis of parallel-design RCTs. Eur Rev Med Pharmacol Sci. 2016;20(13):2926-34.

8. Burnier M., Bakris G., Williams B. Redefining diuretics use in hypertension: why select a thiazide-like diuretic?. J Hypertens. 2019;37(8):1574-86. DOI:10.1097/HJH.0000000000002088.

9. Musini V.M., Nazer M., Bassett K., Wright J.M. Blood pressure-lowering efficacy of monotherapy with thiazide diuretics for primary hypertension. Cochrane Database Syst Rev. 2014;(5):CD003824. DOI:10.1002/14651858.CD003824.pub2.

10. Pareek A.K., Messerli F.H., Chandurkar N.B., et al. Efficacy of Low-Dose Chlorthalidone and Hydrochlorothiazide as Assessed by 24-h Ambulatory Blood Pressure Monitoring. J Am Coll Cardiol. 2016;67(4):379-89. DOI:10.1016/j.jacc.2015.10.083.

11. Fagard R.H., Thijs L., Staessen J.A., et al. Night-day blood pressure ratio and dipping pattern as predictors of death and cardiovascular events in hypertension. J Hum Hypertens. 2009;23(10):645-53. DOI:10.1038/jhh.2009.9.

12. Boggia J., Li Y., Thijs L., et al. Prognostic accuracy of day versus night ambulatory blood pressure: a cohort study. Lancet. 2007;370(9594):1219-29. DOI:10.1016/S0140-6736(07)61538-4.

13. O'Brien E., Parati G., Stergiou G., et al. European Society of Hypertension position paper on ambulatory blood pressure monitoring. J Hypertens. 2013;31(9):1731-68. DOI:10.1097/HJH.0b013e328363e964.

14. Zhang Y., Agnoletti D., Safar M.E., Blacher J. Effect of antihypertensive agents on blood pressure variability: the Natrilix SR versus candesartan and amlodipine in the reduction of systolic blood pressure in hypertensive patients (X-CELLENT) study. Hypertension. 2011;58(2):155-60. DOI:10.1161/HYPERTENSIONAHA.111.174383.

15. Остроумова О.Д., Борисова Е.В., Остроумова Т.М., Кочетков А.И. Вариабельность артериального давления в течение суток: прогностическое значение, методы оценки и влияние антигипертензивной терапии. Кардиология. 2017;57(12):62-72]. DOI:10.18087/cardio.2017.12.10068.

16. Tatasciore А., Renda G., Zimarino M., et al. Awake Systolic Blood Pressure Variability Correlates With Target-Organ Damage in Hypertensive Subjects. Hypertension. 2007;50:325-32.

17. Ozawa M., Tamura K., Okano Y., et al. Blood pressure variability as well as blood pressure level is important for left ventricular hypertrophy and brachial-ankle pulse wave velocity in hypertensives. Clin Exp Hypertens. 2009;31(8):669-79. DOI:10.3109/10641960903407033.

18. Madden J.M., O'Flynn A.M., Fitzgerald A.P., Kearney P.M. Correlation between short-term blood pressure variability and left-ventricular mass index: a meta-analysis. Hypertens Res. 2016;39(3):171-7. DOI:10.1038/hr.2015.126.

19. Mancia G., Parati G., Hennig M., et al. Relation between blood pressure variability and carotid artery damage in hypertension: baseline data from the European Lacidipine Study on Atherosclerosis (ELSA). J Hypertens. 2001;19(11):1981-9. DOI:10.1097/00004872-200111000-00008.

20. Kawai T., Ohishi M., Kamide K., et al. Differences between daytime and nighttime blood pressure variability regarding systemic atherosclerotic change and renal function. Hypertens Res. 2013;36(3):232-9. DOI:10.1038/hr.2012.162.

21. Wang S., Li J., Zhou X., et al. Comparison between the effects of hydrochlorothiazide and indapamide on the kidney in hypertensive patients inadequately controlled with losartan. J Hum Hypertens. 2017;31(12):848-54. DOI:10.1038/jhh.2017.51.

22. Senior R., Imbs J.L., Bory M., et al. Indapamide reduces hypertensive left ventricular hypertrophy: an international multicenter study. J Cardiovasc Pharmacol. 1993;22 Suppl 6:S106-S110.

23. Roush G.C., Abdelfattah R., Song S., et al. Hydrochlorothiazide and alternative diuretics versus reninangiotensin system inhibitors for the regression of left ventricular hypertrophy: a head-to-head metaanalysis. J Hypertens. 2018;36(6):1247-55. DOI:10.1097/HJH.0000000000001691.

24. Vinereanu D., Dulgheru R., Magda S., et al. The effect of indapamide versus hydrochlorothiazide on ventricular and arterial function in patients with hypertension and diabetes: results of a randomized trial. Am Heart J. 2014;168(4):446-56. DOI:10.1016/j.ahj.2014.06.010.

25. Colussi G., Da Porto A., Cavarape A. Hypertension and type 2 diabetes: lights and shadows about causality. J Hum Hypertens. 2020;34(2):91-3. DOI:10.1038/s41371-019-0268-x.

26. Weidmann P., de Courten M., Bohlen L. Insulin resistance, hyperinsulinemia and hypertension. J Hy-pertens Suppl. 1993;11(5):S27-38.

27. Marre M., Puig J.G., Kokot F., et al. Equivalence of indapamide SR and enalapril on microalbuminuria reduction in hypertensive patients with type 2 diabetes: the NESTOR Study. J Hypertens. 2004;22(8):1613-22. DOI:10.1097/01.hjh.0000133733.32125.09.

28. Bahtiyar G., Gutterman D., Lebovitz H. Heart Failure: a Major Cardiovascular Complication of Diabetes Mellitus. Curr Diab Rep. 2016;16(11):116. DOI:10.1007/s11892-016-0809-4.

29. Zhang Y., Agnoletti D., Wang J.G., et al. Natriuresis and blood pressure reduction in hypertensive patients with diabetes mellitus: the NESTOR study. J Am Soc Hypertens. 2015;9(1):21-8. DOI:10.1016/j.jash.2014.10.003.

30. Beckett N.S., Peters R., Fletcher A.E., et al. Treatment of hypertension in patients 80 years of age or older. N Engl J Med. 2008;358(18):1887-98. DOI:10.1056/NEJMoa0801369.

31. Donkor E.S. Stroke in the 21st Century: A Snapshot of the Burden, Epidemiology, and Quality of Life. Stroke Res Treat. 2018;2018:3238165. DOI:10.1155/2018/3238165.

32. Wajngarten M., Silva G.S. Hypertension and Stroke: Update on Treatment. Eur Cardiol. 2019;14(2):111-5. DOI:10.15420/ecr.2019.11.1.

33. Pistoia F., Sacco S., Degan D., et al. Hypertension and Stroke: Epidemiological Aspects and Clinical Evaluation. High Blood Press Cardiovasc Prev. 2016;23(1):9-18. DOI:10.1007/s40292-015-0115-2.

34. Guzik A., Bushnell C. Stroke Epidemiology and Risk Factor Management. Continuum (Minneap Minn). 2017;23(1, Cerebrovascular Disease):15-39. DOI:10.1212/CON.0000000000000416.

35. Leung A.A., Daskalopoulou S.S., Dasgupta K., et al. Hypertension Canada's 2017 Guidelines for Diagnosis, Risk Assessment, Prevention, and Treatment of Hypertension in Adults. Can J Cardiol. 2017;33(5):557-76. DOI:10.1016/j.cjca.2017.03.005.

36. Whelton P.K., Carey R.M., Aronow W.S., et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. 2018;71(6):1269-324. DOI:10.1161/HYP.0000000000000066.

37. Task Force of the Latin American Society of Hypertension. Guidelines on the management of arterial hypertension and related comorbidities in Latin America. J Hypertens. 2017;35(8):1529-45. DOI:10.1097/HJH.0000000000001418.

38. Tzourio C., Anderson C., Chapman N., et al. Effects of blood pressure lowering with perindopril and indapamide therapy on dementia and cognitive decline in patients with cerebrovascular disease. Arch Intern Med. 2003;163(9):1069-75. DOI:10.1001/archinte.163.9.1069.

39. PATS Collaborating Group. Post-stroke antihypertensive treatment study. A preliminary result. Chin Med J (Engl). 1995 Sep;108(9):710-7.

40. Chen P., Chaugai S., Zhao F., Wang D.W. Cardioprotective Effect of Thiazide-Like Diuretics: A MetaAnalysis. Am J Hypertens. 2015;28(12):1453-63. DOI:10.1093/ajh/hpv050.

41. Olde Engberink R.H., Frenkel W.J., van den Bogaard B., et al. Effects of thiazide-type and thiazide-like diuretics on cardiovascular events and mortality: systematic review and meta-analysis. Hypertension. 2015;65(5):1033-40. DOI:10.1161/HYPERTENSIONAHA.114.05122.

42. Thomopoulos C., Parati G., Zanchetti A. Effects of blood pressure lowering on outcome incidence in hypertension: 4. Effects of various classes of antihypertensive drugs--overview and meta-analyses. J Hypertens. 2015;33(2):195-211. DOI:10.1097/HJH.0000000000000447.

43. Bejan-Angoulvant T., Saadatian-Elahi M., Wright J.M., et al. Treatment of hypertension in patients 80 years and older: the lower the better? A meta-analysis of randomized controlled trials. J Hypertens. 2010;28(7):1366-72. DOI:10.1097/HJH.0b013e328339f9c5.

44. Weidmann P. Metabolic profile of indapamide sustained-release in patients with hypertension: data from three randomised double-blind studies. Drug Saf. 2001;24(15):1155-65. DOI:10.2165/00002018-200124150-00006.

45. Peterzan M.A., Hardy R., Chaturvedi N., Hughes A.D. Meta-analysis of dose-response relationships for hydrochlorothiazide, chlorthalidone, and bendroflumethiazide on blood pressure, serum potassium, and urate. Hypertension. 2012;59(6):1104-9. DOI:10.1161/HYPERTENSIONAHA.111.190637.

46. Savage P.J., Pressel S.L., Curb J.D., et al. Influence of long-term, low-dose, diuretic-based, antihypertensive therapy on glucose, lipid, uric acid, and potassium levels in older men and women with isolated systolic hypertension: The Systolic Hypertension in the Elderly Program. SHEP Cooperative Research Group. Arch Intern Med. 1998;158(7):741-51. DOI:10.1001/archinte.158.7.741.

47. Voyaki S.M., Staessen J.A., Thijs L., et al. Follow-up of renal function in treated and untreated older patients with isolated systolic hypertension. Systolic Hypertension in Europe (Syst-Eur) Trial Investigators. J Hypertens. 2001;19(3):511-9. DOI:10.1097/00004872-200103000-00020.

48. Семенкин А.А., Живилова Л.А., Голев-цова З.Ш., и др. Сравнительная оценка гипотензивных, метаболических и эндотелиальных эффектов индапамидаретарда и гидрохлоротиазида у пациентов с гипертонической болезнью. Кардиология. 2006;46(5):35-9.

49. Emeriau J.P., Knauf H., Pujadas J.O., et al. 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(2):343-50. DOI:10.1097/00004872-200102000-00023.

50. Hypertension in adults: diagnosis and management. NICE Guideline, No. 136. National Guideline Centre (UK). London, UK: National Institute for Health and Care Excellence; 2019. ISBN-13: 9781-4731-3503-1.

51. Gabb G.M., Mangoni A.A., Anderson C.S., et al. Guideline for the diagnosis and management of hypertension in adults - 2016. Med J Aust. 2016;205(2):85-9. DOI:10.5694/mja16.00526.

52. Carey R..M, Whelton P.K. 2017 ACC/AHA Hypertension Guideline Writing Committee. Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: Synopsis of the 2017 American College of Cardiology/American Heart Association Hypertension Guideline. Ann Intern Med. 2018;168(5):351-358. DOI:10.7326/M17-3203.

53. American Diabetes Association. 9. Cardiovascular Disease and Risk Management: Standards of Medical Care in Diabetes-2018. Diabetes Care. 2018;41(Suppl 1):S86-S104. DOI:10.2337/dc18-S009.

54. National Clinical Guideline Centre. Hypertension. The clinical management of primary hypertension in adults (NICE clinical guideline 127). London, UK: National Institute for Health and Care Excellence; 2011.


For citations:

Kochetkov A.I. Thiazide and Thiazide-like Diuretics in the Treatment of Arterial Hypertension: are there Any Differences? Rational Pharmacotherapy in Cardiology. 2020;16(6):994-1001. (In Russ.)

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