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Open Access 01-12-2020 | Chlorthalidone | Systematic review update

Combining angiotensin receptor blockers with chlorthalidone or hydrochlorothiazide – which is the better alternative? A meta-analysis

Authors: Elena Filipova, Stela Dineva, Katya Uzunova, Velichka Pavlova, Krassimir Kalinov, Toni Vekov

Published in: Systematic Reviews | Issue 1/2020

Abstract

Background

Hypertension is a disease with significant clinical and socio-economic consequences. The reduction in cardiovascular mortality and morbidity in patients treated for hypertension is directly related to the magnitude of blood pressure reduction. Diuretics have proven useful for the prevention of cardiovascular complications in addition to a long history of safety and efficacy. The main aim for this meta-analysis is to compare the efficacy of the combination of angiotensin receptor blocker (ARB) and chlorthalidone (CTLD) to the combination of ARB and hydrochlorothiazide (HCTZ) in patients with hypertension.

Methods

A comprehensive literature search was conducted through electronic databases PubMed, MEDLINE, Scopus, PsyInfo, Cochrane, eLIBRARY.ru, http://ClinicalTrials.gov and http://www.clinicaltrialsregister.eu in July 2020 to identify studies that investigate the effect of the combination of angiotensin receptor blocker with chlorthalidone or hydrochlorothiazide on the systolic and diastolic blood pressure in patients with hypertension. Changes in systolic and diastolic blood pressure (BP) expressed as a weighted mean difference (WMD) were our primary outcomes. The random-effects method was chosen as the primary analysis and results were presented with a 95% confidence interval (CI). Sensitivity analysis was performed and bias was assessed.

Results

Our search returned 2745 titles. Of them, 51 full-text articles remained to be subjected to assessment. Comparisons of ARB/HCTZ versus ARB showed changes in BP of −6.89 (−8.09, −5.69) mmHg for systolic BP and − 3.67 (−4.15, −3.19) mmHg for diastolic BP. For the ARB/CTLD versus ARB/HCTZ comparison changes were − 6.30 (−7.30, −5.29) mmHg for systolic BP and − 3.57 (−4.17, 2.98) mmHg for diastolic BP.

Conclusion

Our analysis suggests a small but significant favor for CTLD in blood pressure control when compared to HCTZ. We believe it should be considered as a valuable alternative for HCTZ and an option for fixed dose combinations with an ARB although further research is required.

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Kearney PM, Whelton M, Reynolds K, Muntner P, Whelton PK, He J. Global burden of hypertension: analysis of worldwide data. Lancet. 2005;365:217–23.CrossRef

A global brief on hypertension: silent killer, global public health crisis: World Health Day. World Health Organization;2013. Geneva: World Health Organization; 2013.

Petrov A, Gatchev E, Kalinov K, Filipova E, Uzunova K, Vekov Y. Comparative bioavailability of a newly developed irbesartan 300 mg containing preparation. Hosp Pharm. 2018;5(2):638–46.

Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, et al. Seventh report of the joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure. Hypertension. 2003;42(6):1206–52.CrossRef

Lewington S, Clarke R, Qizilbash N, Peto R, Collins R. Age-specific relevance of usual blood pressure to vascular mortality. Lancet. 2002;360:1903–13.CrossRef

ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT). JAMA. 2002;288:2981–97.CrossRef

Psaty BM, Lumley T, Furberg CD, Schellenbaum G, Pahor M, Alderman, et al. Health outcomes associated with various antihypertensive therapies used as first-line agents. A network meta-analysis. JAMA. 2003;289:2534–44.CrossRef

Roush GC, Ernst ME, Kostis JB, Tandon S, Sica DA. Head-to-head comparisons of hydrochlorothiazide with indapamide and chlorthalidone: antihypertensive and metabolic effects. Hypertension. 2015;65:1041–6.CrossRef

Roush GC, Buddharaju V, Ernst ME. Is chlorthalidone better than hydrochlorothiazide in reducing cardiovascular events in hypertensives? Curr Opin Cardiol. 2013;28:426–32.PubMed

10.

Roush GC, Holford TR, Guddati AK. Chlorthalidone compared with hydrochlorothiazide in reducing cardiovascular events: systematic review and network meta-analyses. Hypertension. 2012;59:1110–7.CrossRef

11.

Dineva S, Uzunova K, Pavlova V, Filipova E, Kalinov K, Vekov T. Comparative efficacy and safety of chlorthalidone and hydrochlorothiazide-meta-analysis. J Hum Hypertens. 2019;33(11):766–74. https://doi.org/10.1038/s41371-019-0255-2.CrossRefPubMedPubMedCentral

12.

Guidelines Subcommittee. 1999 World Health Organization-International Society of Hypertension guidelines for the management of hypertension. J Hypertens. 1999;17(2):151–83.

13.

Mancia G, De Backer G, Dominiczak A, Cifkova R, Fagard R, Germano G, et al. 2007 guidelines for the management of arterial hypertension: the task force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens. 2007;25(6):1105–87.CrossRef

14.

Joint National Committee on Detection, Evaluation and Treatment of High Blood Pressure. The fifth report of the joint National Committee on detection, evaluation and treatment of high blood pressure (JNCV). Arch Intern Med. 1993;153:154–83.CrossRef

15.

Epstein M, Bakris G. Newer approaches to antihypertensive therapy. Use of fixed dose combination therapy. Arch Intern Med. 1996;156:1969–78.CrossRef

16.

James PA, Oparil S, Carter BL, Cushman WC, Dennison-Himmelfarb C, Handler J, 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;311:507–20.CrossRef

17.

Weir MR, Bakris GL. Combination therapy with renin-angiotensin-aldosterone receptor blockers for hypertension: how far have we come? J Clin Hypertens (Greenwich). 2008;10(2):146–52.CrossRef

18.

Sood N, Reinhart KM, Baker WL. Combination therapy for the management of hypertension: a review of the evidence. Am J Health Syst Pharm. 2010;67:885–94.CrossRef

19.

Mimran A, Weir MR. Angiotensin-receptor blockers and diuretics--advantages of combination. Blood Press. 2005;14(1):6–11.CrossRef

20.

Fogari R, Taddei S, Holm-Bentzen M, Baszak J, Melani L, Schumacher K. Efficacy and safety of olmesartan medoxomil 40 mg/hydrochlorothiazide 12.5 mg combination therapy versus olmesartan medoxomil 40 mg monotherapy in patients with moderate to severe hypertension: a randomized, double-blind, parallel-group, multicentre, mult. Clin. Drug Investig. 2010;30(9):581–97. https://doi.org/10.2165/11536710-000000000-00000.CrossRef

21.

Benz JR, Black HR, Graff A, Reed A, Fitzsimmons S, Shi Y. Valsartan and hydrochlorothiazide in patients with essential hypertension. A multiple dose, double-blind, placebo controlled trial comparing combination therapy with monotherapy. J Hum Hypertens. 1998;12(12):861–6. https://doi.org/10.1038/sj.jhh.1000718.CrossRefPubMed

22.

Edes I, Group MS. Combination therapy with candesartan cilexetil 32 mg and hydrochlorothiazide 25 mg provides the full additive antihypertensive effect of the components: a randomized, double-blind, parallel-group study in primary care. Clin Drug Investig. 2009;29(5):293–304.CrossRef

23.

Kwon BJ, Jang SW, Choi KY, Kim DB, Cho EJ, Ihm SH, et al. Comparison of the efficacy between hydrochlorothiazide and chlorthalidone on central aortic pressure when added on to candesartan in treatment-naïve patients of hypertension. Hypertens Res. 2013;36(1):79–84. https://doi.org/10.1038/hr.2012.143.CrossRefPubMed

24.

Lacourciere Y, Martin K. Comparison of a fixed-dose combination of 40 mg telmisartan plus 12.5 mg hydrochlorothiazide with 40 mg telmisartan in the control of mild to moderate hypertension. Am J Ther. 2002;9(2):111–7.CrossRef

25.

Lacourcière Y, Tytus R, O’Keefe D, Lenis J, Orchard R, Martin K. Efficacy and tolerability of a fixed-dose combination of telmisartan plus hydrochlorothiazide in patients uncontrolled with telmisartan monotherapy. J Hum Hypertens. 2001;15(11):763–70. https://doi.org/10.1038/sj.jhh.1001267.CrossRefPubMed

26.

Lacourcière Y, Poirier L, Hebert D, Assouline L, Stolt P, Rehel B, et al. Antihypertensive efficacy and tolerability of two fixed-dose combinations of valsartan and hydrochlorothiazide compared with valsartan monotherapy in patients with stage 2 or 3 systolic hypertension: an 8-week, randomized, double-blind, parallel-group T. Clin Ther. 2005;27(7):1013–21.CrossRef

27.

Makita S, Abiko A, Naganuma Y, Tamada M, Nakamura M. Efficacy of low-dose hydrochlorothiazide in combination with telmisartan on early morning blood pressure in uncontrolled hypertensive patients. Clin Exp Hypertens. 2009;31(2):105–15. https://doi.org/10.1080/10641960802621259.CrossRefPubMed

28.

Rhee MY, Baek SH, Kim W, Park CG, Park SW, Oh BH, et al. Efficacy of fimasartan/hydrochlorothiazide combination in hypertensive patients inadequately controlled by fimasartan monotherapy. Drug Des Devel Ther. 2015;9:2847–54. https://doi.org/10.2147/DDDT.S82098.CrossRefPubMedPubMedCentral

29.

Sachse A, Verboom CN, Jäger B. Efficacy of eprosartan in combination with HCTZ in patients with essential hypertension. J Hum Hypertens. 2002;16(3):169–76. https://doi.org/10.1038/sj.jhh.1001317.CrossRefPubMed

30.

Julius S, Kjeldsen SE, Weber M, Brunner HR, Ekman S, Hansson L, et al. VALUE trial group, outcomes in hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine: the VALUE randomised trial. Lancet. 2004;363:2022–31.CrossRef

31.

Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327(7414):557–60. https://doi.org/10.1136/bmj.327.7414.557.CrossRefPubMedPubMedCentral

32.

Mackay JH, Arcuri KE, Goldberg AI, Snapinn SM, Sweet CS. Losartan and low-dose hydrochlorothiazide in patients with essential hypertension. Arch Intern Med. 1996;156:278–85.CrossRef

33.

Sica D, Bakris GL, White WB, Weber MA, Cushman WC, Huang P, et al. Blood pressure-lowering efficacy of the fixed-dose combination of azilsartan medoxomil and chlorthalidone: a factorial study. J Clin Hypertens. 2012;14(5):284–92. https://doi.org/10.1111/j.1751-7176.2012.00616.x.CrossRef

34.

Cushman WC, Bakris GL, White WB, Weber MA, Sica D, Roberts A, et al. Azilsartan medoxomil plus chlorthalidone reduces blood pressure more effectively than olmesartan plus hydrochlorothiazide in stage 2 systolic hypertension. Hypertension. 2012;60(2):310–8. https://doi.org/10.1161/HYPERTENSIONAHA.111.188284.CrossRefPubMed

35.

Cushman WC, Bakris GL, White WB, Weber MA, Sica D, Roberts A, et al. A randomized titrate-to-target study comparing fixed-dose combinations of azilsartanmedoxomil and chlorthalidone with olmesartan and hydrochlorothiazide in stage-2 systolic hypertension. J Hypertens. 2018;36(4):947–56. https://doi.org/10.1097/HJH.0000000000001647.CrossRefPubMedPubMedCentral

36.

Neutel JM, Cushman WC, Lloyd E, Barger B, Handley A. Comparison of long-term safety of fixed-dose combinations azilsartan medoxomil/chlorthalidone vs olmesartan medoxomil/hydrochlorothiazide. J Clin Hypertens. 2017;19(9):874–83. https://doi.org/10.1111/jch.13009.CrossRef

37.

Gaciong Z, Siński M, Lewandowski J. Blood pressure control and primary prevention of stroke: summary of the recent clinical trial data and meta-analyses. Curr Hypertens Rep. 2013;15(6):559–74. https://doi.org/10.1007/s11906-013-0401-0 PMID: 24158454; PMCID: PMC3838588.CrossRefPubMedPubMedCentral

38.

Makai P, IntHout J, Deinum J, Jenniskens K, Wilt GJV. A network meta-analysis of clinical management strategies for treatment-resistant hypertension: making optimal use of the evidence. J Gen Intern Med. 2017;32(8):921–30. https://doi.org/10.1007/s11606-017-4000-7 Epub 2017 Mar 8. PMID: 28275946; PMCID: PMC5515781.CrossRefPubMedPubMedCentral

39.

Taylor AA, Shoheiber O. Adherence to antihypertensive therapy with fixed-dose amlodipine besylate/benazepril HCl versus comparable component-based therapy. Congest Heart Fail. 2003;9:324–32.CrossRef

40.

Taylor AA, Siragy H, Nesbitt S. Angiotensin receptor blockers: pharmacology, efficacy, and safety. J Clin Hypertens (Greenwich). 2011;13(9):677–86. https://doi.org/10.1111/j.1751-7176.2011.00518.x Epub 2011 Jul 27.CrossRef

41.

Cushman WC, Bakris GL, White WB, Weber MA, Sica D, Roberts A, et al. Efficacy and safety of azilsartan medoximil/chlorthalidone vs olmesartan/HCTZ combinations in stage 2 systolic hypertension. J Clin Hypertens (Greenwich). 2011;13(Suppl 1):162.

42.

National Guideline Centre (UK). Hypertension in adults: diagnosis and management. London: National Institute for Health and Care Excellence (UK); 2019. PMID: 31577399.

43.

Mukete BN, Ferdinand KC. Polypharmacy in older adults with hypertension: a comprehensive review. J Clin Hypertens (Greenwich). 2016;18(1):10–8. https://doi.org/10.1111/jch.12624 Epub 2015 Jul 27. PMID: 26215211.CrossRef

44.

Stuhec M, Gorenc K, Zelko E. Evaluation of a collaborative care approach between general practitioners and clinical pharmacists in primary care community settings in elderly patients on polypharmacy in Slovenia: a cohort retrospective study reveals positive evidence for implementation. BMC Health Serv Res. 2019;19(1):118. https://doi.org/10.1186/s12913-019-3942-3 PMID: 30760276; PMCID: PMC6375190.CrossRefPubMedPubMedCentral

45.

Štuhec M, Potočin I, Stepan D, Ušaj L, Petek Šter M, et al. Potential drug interactions with antibacterials in long-term care facilities analyzed by two interaction checkers. Int J Clin Pharm. 2019;41(4):932–8. https://doi.org/10.1007/s11096-019-00855-x Epub 2019 Jun 6. PMID: 31172409.CrossRefPubMed

46.

Hess NC, Carlson DJ, Inder JD, Jesulola E, McFarlane JR, Smart NA. Clinically meaningful blood pressure reductions with low intensity isometric handgrip exercise. A randomized trial. Physiol Res. 2016;65(3):461–8. https://doi.org/10.33549/physiolres.933120 Epub 2016 Apr 12. PMID: 27070747.CrossRefPubMed

47.

Chrysant SG, Chrysant GS. Antihypertensive efficacy of olmesartan medoxomil alone and in combination with hydrochlorothiazide. Expert Opin Pharmacother. 2004;5(3):657–67.CrossRef

48.

Chrysant SG. Fixed combination therapy of hypertension: focus on valsartan/hydrochlorothiazide combination (Diovan/HCT). Expert Rev Cardiovasc Ther. 2003;1(3):335–43.CrossRef

49.

Lacourcière Y. A new fixed-dose combination for added blood pressure control: telmisartan plus hydrochlorothiazide. J Int Med Res. 2002;30(4):366–79.CrossRef

50.

Maillard M, Burnier M. Telmisartan/hydrochlorothiazide: a new fixed dose combination. Expert Rev Cardiovasc Ther. 2005;3(3):375–86.CrossRef

51.

Melian EB, Jarvis B. Candesartan cilexetil plus hydrochlorothiazide combination: a review of its use in hypertension. Drugs. 2002;62(5):787–816.CrossRef

52.

Ram CV. Antihypertensive efficacy of angiotensin receptor blockers in combination with hydrochlorothiazide: a review of the factorial-design studies. J Clin Hypertens (Greenwich). 2004 Oct;6(10):569–77.CrossRef

53.

Multiple Risk Factor Intervention Trial Research Group. Mortality after 10 1/2 years for hypertensive participants in the multiple risk factor intervention trial. Circulation. 1990;82(5):1616–28.CrossRef

54.

Dorsch M, Gillespie B, Erikson S. Chlorthalidone reduces cardiovascular events compared with hydrochlorothiazide: a retrospective cohort analysis. Hypertension. 2011;57:689–94.CrossRef

55.

Dhalla IA, Gomes T, Yao Z, Nagge J, Persaud N, Hellings C, et al. Chlorthalidone versus hydrochlorothiazide for the treatment of hypertension in older adults: a population-based cohort study. Ann Intern Med. 2013;158:447–55.CrossRef

56.

Ernst M, Carter B, Goerdt C. Comparative antihypertensive effects of hydrochlorothiazide and chlorthalidone on ambulatory and office blood pressure. Hypertension. 2006;47:352–8.CrossRef

57.

Pareek AK, Messerli FH, Chandurkar NB, Dharmadhikari SK, Godbole AV, Kshirsagar PP, et al. Efficacy of lowdose chlorthalidone and hydrochlorothiazide as assessed by 24-h ambulatory blood pressure monitoring. JACC. 2016;67(4):379–89.CrossRef

58.

Peterzan MA, Hardy R, Chaturvedi N, Hughes AD. Meta-analysis of dose response relationships for hydrochlorothiazide, chlorthalidone, and bendroflumethiazide on blood pressure, serum potassium, and urate. Hypertension. 2012;59:1104–9.CrossRef

Title: Combining angiotensin receptor blockers with chlorthalidone or hydrochlorothiazide – which is the better alternative? A meta-analysis
Authors: Elena Filipova
Stela Dineva
Katya Uzunova
Velichka Pavlova
Krassimir Kalinov
Toni Vekov
Publication date: 01-12-2020
Publisher: BioMed Central
Keywords: Chlorthalidone
Diuretics
Hydrochlorothiazide
Hypertension
Hypertension
Published in: Systematic Reviews / Issue 1/2020
Electronic ISSN: 2046-4053
DOI: https://doi.org/10.1186/s13643-020-01457-9

At a glance: The STEP trials

Springer Medicine

Combining angiotensin receptor blockers with chlorthalidone or hydrochlorothiazide – which is the better alternative? A meta-analysis

Abstract

Background

Methods

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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