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Review
. 2014 May 29;2014(5):CD003824.
doi: 10.1002/14651858.CD003824.pub2.

Blood pressure-lowering efficacy of monotherapy with thiazide diuretics for primary hypertension

Vijaya M Musini  1 , Mark Nazer, Ken Bassett, James M Wright
Affiliations
Review

Blood pressure-lowering efficacy of monotherapy with thiazide diuretics for primary hypertension

Vijaya M Musini et al. Cochrane Database Syst Rev. .

Abstract

Background: Hypertension is a modifiable cardiovascular risk factor. Although it is established that low-dose thiazides reduce mortality as well as cardiovascular morbidity, the dose-related effect of thiazides in decreasing blood pressure has not been subject to a rigorous systematic review. It is not known whether individual drugs within the thiazide diuretic class differ in their blood pressure-lowering effects and adverse effects.

Objectives: To determine the dose-related decrease in systolic and/or diastolic blood pressure due to thiazide diuretics compared with placebo control in the treatment of patients with primary hypertension. Secondary outcomes included the dose-related adverse events leading to patient withdrawal and adverse biochemical effects on serum potassium, uric acid, creatinine, glucose and lipids.

Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2014, Issue 1), Ovid MEDLINE (1946 to February 2014), Ovid EMBASE (1974 to February 2014) and ClinicalTrials.gov.

Selection criteria: We included double-blind, randomized controlled trials (RCTs) comparing fixed-dose thiazide diuretic monotherapy with placebo for a duration of 3 to 12 weeks in the treatment of adult patients with primary hypertension.

Data collection and analysis: Two authors independently screened articles, assessed trial eligibility, extracted data and determined risk of bias. We combined data for continuous variables using a mean difference (MD) and for dichotomous outcomes we calculated the relative risk ratio (RR) with 95% confidence interval (CI).

Main results: We included 60 randomized, double-blind trials that evaluated the dose-related trough blood pressure-lowering efficacy of six different thiazide diuretics in 11,282 participants treated for a mean duration of eight weeks. The mean age of the participants was 55 years and baseline blood pressure was 158/99 mmHg. Adequate blood pressure-lowering efficacy data were available for hydrochlorothiazide, chlorthalidone and indapamide. We judged 54 (90%) included trials to have unclear or high risk of bias, which impacted on our confidence in the results for some of our outcomes.In 33 trials with a baseline blood pressure of 155/100 mmHg, hydrochlorothiazide lowered blood pressure based on dose, with doses of 6.25 mg, 12.5 mg, 25 mg and 50 mg/day lowering blood pressure compared to placebo by 4 mmHg (95% CI 2 to 6, moderate-quality evidence)/2 mmHg (95% CI 1 to 4, moderate-quality evidence), 6 mmHg (95% CI 5 to 7, high-quality evidence)/3 mmHg (95% CI 3 to 4, high-quality evidence), 8 mmHg (95% CI 7 to 9, high-quality evidence)/3 mmHg (95% CI 3 to 4, high-quality evidence) and 11 mmHg (95% CI 6 to 15, low-quality evidence)/5 mmHg (95% CI 3 to 7, low-quality evidence), respectively.Direct comparison of doses did not show evidence of dose dependence for blood pressure-lowering for any of the other thiazides for which RCT data were available: bendrofluazide, chlorthalidone, cyclopenthiazide, metolazone or indapamide.In seven trials with a baseline blood pressure of 163/88 mmHg, chlorthalidone at doses of 12.5 mg to 75 mg/day reduced average blood pressure compared to placebo by 12.0 mmHg (95% CI 10 to 14, low-quality evidence)/4 mmHg (95% CI 3 to 5, low-quality evidence).In 10 trials with a baseline blood pressure of 161/98 mmHg, indapamide at doses of 1.0 mg to 5.0 mg/day reduced blood pressure compared to placebo by 9 mmHg (95% CI 7 to 10, low-quality evidence)/4 (95% CI 3 to 5, low-quality evidence).We judged the maximal blood pressure-lowering effect of the different thiazides to be similar. Overall, thiazides reduced average blood pressure compared to placebo by 9 mmHg (95% CI 9 to 10, high-quality evidence)/4 mmHg (95% CI 3 to 4, high-quality evidence).Thiazides as a class have a greater effect on systolic than on diastolic blood pressure, therefore thiazides lower pulse pressure by 4 mmHg to 6 mmHg, an amount that is greater than the 3 mmHg seen with angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs) and renin inhibitors, and the 2 mmHg seen with non-selective beta-blockers. This is based on an informal indirect comparison of results observed in other Cochrane reviews on ACE inhibitors, ARBs and renin inhibitors compared with placebo, which used similar inclusion/exclusion criteria to the present review.Thiazides reduced potassium, increased uric acid and increased total cholesterol and triglycerides. These effects were dose-related and were least for hydrochlorothiazide. Chlorthalidone increased serum glucose but the evidence was unclear for other thiazides. There is a high risk of bias in the metabolic data. This review does not provide a good assessment of the adverse effects of these drugs because there was a high risk of bias in the reporting of withdrawals due to adverse effects.

Authors' conclusions: This systematic review shows that hydrochlorothiazide has a dose-related blood pressure-lowering effect. The mean blood pressure-lowering effect over the dose range 6.25 mg, 12.5 mg, 25 mg and 50 mg/day is 4/2 mmHg, 6/3 mmHg, 8/3 mmHg and 11/5 mmHg, respectively. For other thiazide drugs, the lowest doses studied lowered blood pressure maximally and higher doses did not lower it more. Due to the greater effect on systolic than on diastolic blood pressure, thiazides lower pulse pressure by 4 mmHg to 6 mmHg. This exceeds the mean 3 mmHg pulse pressure reduction achieved by ACE inhibitors, ARBs and renin inhibitors, and the 2 mmHg pulse pressure reduction with non-selective beta-blockers as shown in other Cochrane reviews, which compared these antihypertensive drug classes with placebo and used similar inclusion/exclusion criteria.Thiazides did not increase withdrawals due to adverse effects in these short-term trials but there is a high risk of bias for that outcome. Thiazides reduced potassium, increased uric acid and increased total cholesterol and triglycerides.

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Conflict of interest statement

Vijaya Musini: none known.

Mark nazer: none known.

Ken Bassett: none known.

James Wright: none known.

Figures

1
1
Study flow diagram.
2
2
'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.
3
3
'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
4
4
Funnel plot of comparison: 7 Thiazide versus placebo, outcome: 7.1 Systolic blood pressure.
5
5
Dose‐related effect of hydrochlorothiazide on systolic blood pressure
6
6
Dose‐related effect of hydrochlorothiazide on diastolic blood pressure
1.1
1.1. Analysis
Comparison 1 Bendrofluazide versus placebo, Outcome 1 Systolic blood pressure.
1.2
1.2. Analysis
Comparison 1 Bendrofluazide versus placebo, Outcome 2 Diastolic blood pressure.
1.3
1.3. Analysis
Comparison 1 Bendrofluazide versus placebo, Outcome 3 Withdrawals due to adverse effects.
1.4
1.4. Analysis
Comparison 1 Bendrofluazide versus placebo, Outcome 4 Serum potassium mmol/L.
1.5
1.5. Analysis
Comparison 1 Bendrofluazide versus placebo, Outcome 5 Serum uric acid µmol/L.
1.6
1.6. Analysis
Comparison 1 Bendrofluazide versus placebo, Outcome 6 Serum creatinine µmol/L.
1.7
1.7. Analysis
Comparison 1 Bendrofluazide versus placebo, Outcome 7 Serum blood glucose mmol/L.
1.8
1.8. Analysis
Comparison 1 Bendrofluazide versus placebo, Outcome 8 Total cholesterol mmol/L.
1.9
1.9. Analysis
Comparison 1 Bendrofluazide versus placebo, Outcome 9 Triglycerides mmol/L.
2.1
2.1. Analysis
Comparison 2 Cyclopenthiazide versus placebo, Outcome 1 Systolic blood pressure.
2.2
2.2. Analysis
Comparison 2 Cyclopenthiazide versus placebo, Outcome 2 Diastolic blood pressure.
2.3
2.3. Analysis
Comparison 2 Cyclopenthiazide versus placebo, Outcome 3 Serum potassium µmol/L.
2.4
2.4. Analysis
Comparison 2 Cyclopenthiazide versus placebo, Outcome 4 Serum uric acid µmol/L.
2.5
2.5. Analysis
Comparison 2 Cyclopenthiazide versus placebo, Outcome 5 Total cholesterol mmol/L.
2.6
2.6. Analysis
Comparison 2 Cyclopenthiazide versus placebo, Outcome 6 Triglycerides mmol/L.
3.1
3.1. Analysis
Comparison 3 Metolazone versus placebo, Outcome 1 Systolic blood pressure.
3.2
3.2. Analysis
Comparison 3 Metolazone versus placebo, Outcome 2 Diastolic blood pressure.
4.1
4.1. Analysis
Comparison 4 Chlorthalidone versus placebo, Outcome 1 Systolic blood pressure.
4.2
4.2. Analysis
Comparison 4 Chlorthalidone versus placebo, Outcome 2 Diastolic blood pressure.
4.3
4.3. Analysis
Comparison 4 Chlorthalidone versus placebo, Outcome 3 Withdrawals due to adverse events.
4.4
4.4. Analysis
Comparison 4 Chlorthalidone versus placebo, Outcome 4 Serum potassium mmol/L.
4.5
4.5. Analysis
Comparison 4 Chlorthalidone versus placebo, Outcome 5 Serum uric acid µmol/L.
4.6
4.6. Analysis
Comparison 4 Chlorthalidone versus placebo, Outcome 6 Serum blood glucose mmol/L.
4.7
4.7. Analysis
Comparison 4 Chlorthalidone versus placebo, Outcome 7 HDL cholesterol mmol/L.
4.8
4.8. Analysis
Comparison 4 Chlorthalidone versus placebo, Outcome 8 Total cholesterol mmol/L.
4.9
4.9. Analysis
Comparison 4 Chlorthalidone versus placebo, Outcome 9 Triglycerides mmol/L.
5.1
5.1. Analysis
Comparison 5 Hydrochlorothiazide versus placebo, Outcome 1 Systolic blood pressure.
5.2
5.2. Analysis
Comparison 5 Hydrochlorothiazide versus placebo, Outcome 2 Diastolic blood pressure.
5.3
5.3. Analysis
Comparison 5 Hydrochlorothiazide versus placebo, Outcome 3 Withdrawals due to adverse events.
5.4
5.4. Analysis
Comparison 5 Hydrochlorothiazide versus placebo, Outcome 4 Serum potassium mmol/L.
5.5
5.5. Analysis
Comparison 5 Hydrochlorothiazide versus placebo, Outcome 5 Serum uric acid µmol/L.
5.6
5.6. Analysis
Comparison 5 Hydrochlorothiazide versus placebo, Outcome 6 Serum creatinine µmol/L.
5.7
5.7. Analysis
Comparison 5 Hydrochlorothiazide versus placebo, Outcome 7 Serum blood glucose mmol/L.
5.8
5.8. Analysis
Comparison 5 Hydrochlorothiazide versus placebo, Outcome 8 HDL cholesterol mmol/L.
5.9
5.9. Analysis
Comparison 5 Hydrochlorothiazide versus placebo, Outcome 9 Total cholesterol mmol/L.
5.10
5.10. Analysis
Comparison 5 Hydrochlorothiazide versus placebo, Outcome 10 Triglycerides mmol/L.
6.1
6.1. Analysis
Comparison 6 Indapamide versus placebo, Outcome 1 Systolic blood pressure.
6.2
6.2. Analysis
Comparison 6 Indapamide versus placebo, Outcome 2 Diastolic blood pressure.
6.3
6.3. Analysis
Comparison 6 Indapamide versus placebo, Outcome 3 Withdrawals due to adverse events.
6.4
6.4. Analysis
Comparison 6 Indapamide versus placebo, Outcome 4 Serum potassium mmol/L.
6.5
6.5. Analysis
Comparison 6 Indapamide versus placebo, Outcome 5 Serum uric acid µmol/L.
6.6
6.6. Analysis
Comparison 6 Indapamide versus placebo, Outcome 6 Serum creatinine µmol/L.
6.7
6.7. Analysis
Comparison 6 Indapamide versus placebo, Outcome 7 Serum blood glucose mmol/L.
6.8
6.8. Analysis
Comparison 6 Indapamide versus placebo, Outcome 8 HDL cholesterol mmol/L.
6.9
6.9. Analysis
Comparison 6 Indapamide versus placebo, Outcome 9 Total cholesterol mmol/L.
6.10
6.10. Analysis
Comparison 6 Indapamide versus placebo, Outcome 10 Triglycerides mmol/L.
7.1
7.1. Analysis
Comparison 7 Thiazide versus placebo, Outcome 1 Systolic blood pressure.
7.2
7.2. Analysis
Comparison 7 Thiazide versus placebo, Outcome 2 Diastolic blood pressure.
7.3
7.3. Analysis
Comparison 7 Thiazide versus placebo, Outcome 3 Serum potassium mmol/L.
7.4
7.4. Analysis
Comparison 7 Thiazide versus placebo, Outcome 4 Serum uric acid µmol/L.
7.5
7.5. Analysis
Comparison 7 Thiazide versus placebo, Outcome 5 Serum creatinine µmol/L.
7.6
7.6. Analysis
Comparison 7 Thiazide versus placebo, Outcome 6 Serum blood glucose mmol/L.
7.7
7.7. Analysis
Comparison 7 Thiazide versus placebo, Outcome 7 Serum total cholesterol mmol/L.
7.8
7.8. Analysis
Comparison 7 Thiazide versus placebo, Outcome 8 Serum HDL mmol/L.
7.9
7.9. Analysis
Comparison 7 Thiazide versus placebo, Outcome 9 Triglycerides.
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References

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Pordy 1994 {published data only}
    1. Pordy RC and the Cilazapril/Hydrochlorothiazide 4x3 Factorial Design Study Group. Cilazapril plus hydrochlorothiazide: improved efficacy without reduced safety in mild to moderate hypertension. A double‐blind placebo‐controlled multicenter study of factorial design. Cardiology 1994;85:311‐22. - PubMed
Prisant 2000 {published data only}
    1. Prisant LM. Ambulatory blood pressure profiles in patients treated with once‐daily diltiazem extended‐release or indapamide alone or in combination. American Journal of Therapeutics 2000;7:177‐84. - PubMed
Roque 1996 {published data only}
    1. Roque F, Mon G, Cravero C, Courreges J, et al. Antihypertensive efficacy of hydrochlorothiazide 12.5 mg in patients with mild to moderate hypertension. Advances in Therapy 1996;13(5):284‐91.
Saruta 2007 {published data only}
    1. Saruta T, Ogihara T, Matsuoka H, Suzuki H, Toki M, Hirayama Y, et al. Antihypertensive efficacy and safety of fixed‐dose combination therapy with losartan plus hydrochlorothiazide in Japanese patients with essential hypertension. Hypertension Research 2007;30(8):729‐39. - PubMed
Schmieder 2009 {published data only}
    1. Schmieder RE, Philipp T, Guerediaga J, Gorostidi M, Smith B, Weissbach N, et al. Long‐term antihypertensive efficacy and safety of the oral direct renin inhibitor aliskiren. A 12‐month randomized, double‐blind comparator trial with hydrochlorothiazide. Circulation 2009;119:417‐25. - PubMed
Schoenberger 1995 {published data only}
    1. MacKay JH, Arcuri KE, Goldberg AI, Snapinn SM, Sweet CS. Losartan and low‐dose hydrochlolorthiazide in patients with essential hypertension. Archives of Internal Medicine 1996;156:278‐85. - PubMed
    1. Schoenberger JA, Bauer J, Barden LP, Brown R, Byyny R, Cohen J, et al. Losartan with hydrochlorothiazide in the treatment of hypertension. Journal of Hypertension 1995;13(Suppl 1):S43‐7. - PubMed
Scholze 1993 {published data only}
    1. Scholze J, Breitstadt A, Cairns V, Bauer B, Bender N, Priestley C, et al. Short report: ramipril and hydrochlorothiazide combination therapy in hypertension: a clinical trial of factorial design. The East Germany Collaborative Trial Group. Journal of Hypertension 1993;11(2):217‐21. - PubMed
Siegel 1992 {published data only}
    1. Siegel D, Hulley SB, Black DM, Cheitlin MD, Sebastian A, Seeley DG, et al. Diuretics, serum, and intracellular electrolyte levels, and ventricular arrhythmias in hypertensive men. JAMA 1992;267(8):1083‐9. - PubMed
    1. Siegel D, Saliba P, Haffner S. Glucose and insulin levels during diuretic therapy in hypertensive men. Hypertension 1994;23(6 Pt 1):688‐94. - PubMed
Soltero 1989 {published data only}
    1. Soltero I, Fuenmayor I, Colmenares A, et al. Action of indapamide on lipid profiles: a double blind cross over study. Current Therapeutic Research 1989;46(1):163‐72.
Taylor 1988 {published data only}
    1. Taylor DR, Constable J, Sonnekus M, Milne FJ. Effect of indapamide on serum and red cell cations, with and without magnesium supplementation, in subjects with mild hypertension. South African Medical Journal 1988;74(6):273‐6. - PubMed
Vardan 1987 {published data only}
    1. Vardan S, Mehrotra KG, Mookherjee S, Willsey GA, Gens JD, Green DE. Efficacy and reduced metabolic side effects of a 15‐mg chlorthalidone formulation in the treatment of mild hypertension. A multicenter study. JAMA 1987;258(4):484‐8. - PubMed
Villamil 2007 {published data only}
    1. Villamil A, Chrysant SG, Calhoun D, Schober B, Hsu H, Matrisciano‐Dimichino L, et al. Renin inhibition with aliskiren provides additive antihypertensive efficacy when used in combination with hydrochlorothiazide. Journal of Hypertension 2007;25:217‐26. - PubMed
Weidler 1995 {published data only}
    1. Weidler D, Jallad NS, Curry C, Ferdinand K, Jain AK, Schnaper HW, et al. Efficacious response with lower dose indapamide therapy in the treatment of elderly patients with mild to moderate hypertension. Journal of Clinical Pharmacology 1995;35:45‐51. - PubMed
Weir 1992 {published data only}
    1. Weir MR, Weber MA, Punzi HA, Serfer HM, Rosenblatt S, Cady WJ. A dose escalation trial comparing the combination of diltiazem SR and hydrochlorothiazide with the monotherapies in patients with essential hypertension. Journal of Human Hypertension 1992;6(2):133‐8. - PubMed
Yodfat 1994 {published data only}
    1. Yodfat Y, Zimilchman R and the Israeli‐Italian Cilazapril/Hydrochlorothiazide Research Study Group. Dose‐finding and dose justification of once‐daily cilazapril in combination with hydrochlorothiazide in non‐obese patients with mild‐to‐moderate essential hypertension. Journal of Drug Development 1994;6(3):117‐21.

References to studies excluded from this review

Amery 1978 {published data only}
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Anavekar 1979 {published data only}
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Bateman 1979 {published data only}
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Borghi 1993 {published data only}
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Carretta 1988a {published data only}
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Chalmers 1976 {published data only}
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Chalmers 1982 {published data only}
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Chalmers 1986 {published data only}
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Christiansen 1981 {published data only}
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Consoli 1985 {published data only}
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Cranston 1962 {published data only}
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Crowe 1987 {published data only}
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Datta 1989 {published data only}
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Davis 1993 {published data only}
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Dean 1971 {published data only}
    1. Dean G, Louw S, Hersch C, Kirsten HO, Brereton DN, Finnemore L, et al. A double‐blind trial in hypertension comparing Baycaron (FBA 1500), hydrochlorothiazide and placebo. South African Medical Journal 1971;45(12):323. - PubMed
Durel 1992 {published data only}
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Eames 2005 {published data only}
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Elliot 1991 {published data only}
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Erwteman 1984 {published data only}
    1. Erwteman TM, Nagelkerke N, Lubsen J, Koster M, Dunning AJ. β Blockade, diuretics, and salt restriction for the management of mild hypertension: a randomised double blind trial. British Medical Journal 1984;289:406‐9. - PMC - PubMed
Fagard 1976 {published data only}
    1. Fagard R, Amery A, Plaen J‐F, Lijnen P, Missotten A. Relative value of beta blockers and thiazides for initiating antihypertensive therapy. Acta Cardiologica 1976;31(5):411‐26. - PubMed
Fernandez 1980 {published data only}
    1. Fernandez PG, Zachariah PK, Bryant DG, Missan SS. Antihypertensive efficacy of alpha‐methyldopa, chlorothiazide and supres‐150 (alpha methyldopa‐chlorothiazide). Canadian Medical Association Journal 1980;123:284‐7. - PMC - PubMed
Flack 2001 {published data only}
    1. Flack JM, Saunders E, Gradman A, Kraus WE, Lester M, Pratt JH, et al. Antihypertensive efficacy and safety of losartan alone and in combination with hydrochlorothiazide in adult African Americans with mild to moderate hypertension. Clinical Therapeutics 2001;23(8):1193‐208. - PubMed
Gall 1992 {published data only}
    1. Gall MA, Rossing P, Skott P, Hommel E, Mathiesen ER, Geradel LU, et al. Placebo‐controlled comparison of captopril, metoprolol, and hydrochlorothiazide therapy in non‐insulin dependent diabetic patients with primary hypertension. American Journal of Hypertension 1992;5(5 Pt 1):257‐65. - PubMed
Galloway 1974 {published data only}
    1. Galloway DB, Beattie AG, Petrie JC. Practolol and bendrofluazide in treatment of hypertension. British Heart Journal 1974;36:867‐87. - PMC - PubMed
Gerber 1985 {published data only}
    1. Gerber A, Weidmann P, Bianchetti MG, Ferrier C, Laederach K, Mordasini R, et al. Serum lipoproteins during treatment with the antihypertensive agent indapamide. Hypertension 1985;7(6 Suppl II):II164‐9. - PubMed
Gleerup 1996 {published data only}
    1. Gleerup G, Petersen JR, Mehelsen J, Winther K. Effect of spirapril and hydrochlorothiazide on platelet function and euglobulin clot lysis time in patients with mild hypertension. Angiology 1996;47(10):951‐6. - PubMed
Goldman 1980 {published data only}
    1. Goldman AI, Steele BW, Schnaper HW, Fitz AE, Frohlich ED, Perry HM Jr. Serum lipoprotein levels during chlorthalidone therapy. A Veterans Administration‐National Heart, Lung, and Blood Institute Cooperative Study on Antihypertensive Therapy: mild hypertension. JAMA 1980;244(15):1691‐5. - PubMed
Grimm 1981 {published data only}
    1. Grimm RH, Leon AS, Hunninghake DB, Lenz K, Hannan P, Blackburn H. Effect of thiazide diuretics on plasma lipids and lipoproteins in mildly hypertensive patients. Annals of Internal Medicine 1981;1(94):7‐11. - PubMed
Grimm 2002 {published data only}
    1. Grimm Jr. RH, Black H, Rowen R, Lewin A, Shi H, Ghadanfar M and the Amlodipine study group. Amlodipine versus chlorthalidone versus placebo in the treatment of stage I isolated systolic hypertension. American Journal of Hypertension 2002;15(1 Part 1):31‐6. - PubMed
Hobbs 1964 {published data only}
    1. Hobbs LF. Essential hypertension. Management with reserpine‐thiazide combination and the separate components (report of a double‐blind study). Western Medicine ‐ the Medical Journal of the West 1964;5:316‐9. - PubMed
Horvath 1979 {published data only}
    1. Horvath JS, Caterson RJ, Collett P, Duggin GG, Kelly DH, Tiller DJ. Labetolol and bendrofluazide: comparison of their antihypertensive effects. Medical Journal of Australia 1979;1:626‐62. - PubMed
Jackson 1986 {published data only}
    1. Jackson G, Rowland M, Adam G, MacFarlane E, Jackson PG. Placebo controlled double‐blind randomised cross‐over trial of atenolol, hydrochlorothiazide and amiloride, and the combination (Kalten) in patients over 60 years of age. British Journal of Clinical Practice 1986;40(6):230‐4. - PubMed
Jain 1985 {published data only}
    1. Jain AK, Hiremath A, Michael R, Ryan JR, McMahon FG. Clonidine and guanfacine in hypertension. Clinical Pharmacology and Therapeutics 1985;37(3):271‐6. - PubMed
Johnson 1986 {published data only}
    1. Johnson BF, Saunders R, Hickler R, Marwaha R, Johnson J. The effect of thiazide diuretics upon plasma lipoproteins. Journal of Hypertension 1986;4:235‐9. - PubMed
Jueng 1987 {published data only}
    1. Jueng C, Halperin AK, Hashimoto F, Callender K. Nifedipine GITS and hydrochlorothiazide in essential hypertension. Journal of Clinical Hypertension 1987;3:695‐703. - PubMed
Koskelainen 1985 {published data only}
    1. Koskelainen J, Turpeinen T, Lehto H, et al. Metabolic effects of hydrochlorothiazide and hydrochlorothiazide‐amiloride and trichlormethiazide‐triamterene combinations. Current Therapeutic Research 1985;37(3):554‐65.
Kuramoto 1981 {published data only}
    1. Kuramoto K, Matsushita S, Kuwajima I, Murakami M. Prospective study on the treatment of mild hypertension in the aged. Japanese Heart Journal 1981;22(1):75‐85. - PubMed
Kuramoto 1985 {published data only}
    1. Kuramoto K, Masuyama Y. Comparison of the clinical usefulness of diuretics in elderly and younger essential hypertension‐double blind trial using tripamide. Nippon Ronen Igakkai Zasshi (Japanese Journal of Geriatrics) 1985;22(4):346‐53. - PubMed
Lechi 1982 {published data only}
    1. Lechi A, Pomari S, Berto R, Buniotto P, Parrinello A, Marini F, et al. Clinical evaluation of labetalol alone and combined with chlorthalidone in essential hypertension: a double‐blind multicentre controlled study. European Journal of Clinical Pharmacology 1982;22:289‐93. - PubMed
Lutterodt 1980 {published data only}
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Materson 1993 {published data only}
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    1. Materson BJ, Reda DJ, Cushman WC, Massie BM, Freis ED, Kochar MS, et al. Single‐drug therapy for hypertension in men. A comparison of six antihypertensive agents with placebo. New England Journal of Medicine 1993;328(13):914‐21. - PubMed
Maus 1978 {published data only}
    1. Maus Y, Rorive G. Comparison using the double‐blind method of the hypotensive action of indapamide and that of another salidiuretic agent, chlorthalidone [Comparison selon la method du double insu de laction hypotensive de lindapamide avec celle dun autre salidiuretique la chlorthalidone]. Revue Medicale de Liege 1978;33(10):365‐8. - PubMed
Maximilian 1970 {published data only}
    1. Maximilian V, Gavrila F, Zeana C, Barbulescu I, Dimitriu CG. Effectiveness of a compound preparation (DCR 515) in the treatment of arterial hypertension (double‐blind test) [Eficacitatea unui preparat compus (DCR 515) in tratamentul hipertensiunii arteriale (test dublu orb)]. Medicina Interna 1970;22(3):297‐305. - PubMed
McCorvey 1993 {published data only}
    1. McCorvey E Jr, Wright JT Jr, Culbert JP, McKenny M, Proctor JD, Annet MP. Effect of hydrochlorothiazide, enalapril, and propranolol on quality of life and cognitive and motor function in hypertensive patients. Clinical Pharmacy 1993;12:300‐5. - PubMed
Merrill 1987 {published data only}
    1. Merrill BA, Byyny RL, Carr A, Dauer AD, Kazilionis JE, Lester FM, et al. Lisinopril/HCTZ in essential hypertension. Pharmacology and Therapeutics 1987;41(2):227 [Abstract].
Milliez 1975 {published data only}
    1. Milliez P, Tehaedakoff P. Antihypertensive activity of a new agent, indapamide: a double‐blind study. Current Medical Research Opinion 1975;3:9‐15. - PubMed
Morgan 2001 {published data only}
    1. Morgan TO, Anderson AIE, MacInnis RJ. ACE inhibitors, beta‐blockers, calcium blockers, and diuretics for the control of systolic hypertension. American Journal of Hypertension 2001;14(3):241‐7. - PubMed
Moser 1986 {published data only}
    1. Moser M. Low dose diuretic therapy for hypertension. Clinical Therapeutics 1986;8(5):554‐62. - PubMed
MRC Working Party 1983 {published data only}
    1. MRC Working Party on Mild Hypertension. Ventricular extrasystoles during thiazide treatment: sub‐study of MRC mild hypertension trial. British Medical Journal 1983;287:1249‐53. - PMC - PubMed
Muiesan 1987 {published data only}
    1. Muiesan G, Agabiti‐Rosei E, Buoninconti R, Cagli V, Carotti A, Corea L, et al. Antihypertensive efficacy and tolerability of captopril in the elderly: comparison with hydrochlorothiazide and placebo in a multicentre, double‐blind study. Journal of Hypertension 1987;5(Suppl 5):S599‐602. - PubMed
Myers 1982 {published data only}
    1. Myers MG, Wein ME, Fisher RH, Gryfe CI, Shulman HS. Unnecessary diuretic therapy in the elderly. Age and Aging 1982;11:213‐21. - PubMed
Myers 1983 {published data only}
    1. Myers MG. Effects of atenolol and hydrochlorothiazide on blood pressure and plasma catecholamines in essential hypertension. Hypertension 1983;5:591‐6. - PubMed
Okun 1978 {published data only}
    1. Okun R, Beg M. Tricynafen and hydrochlorothiazide in hypertension. Clinical Pharmacology and Therapeutics 1978;23(6):703‐11. - PubMed
Okun 1979 {published data only}
    1. Okun R, Beg MA. A double‐blind study of tienilic acid with two year follow‐up of patients with mild to moderate essential hypertension. Postgraduate Medical Journal 1979;55(Suppl 3):103‐9. - PubMed
PATS Col. Group 1995 {published data only}
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Petersen 1996 {published data only}
    1. Petersen JR, Drabaek H, Gleerup G, Mehlsen J, Petersen LJ, Winther K. ACE inhibitor with spirapril improves diastolic function at rest independent of vasodilation during treatment with spirapril in mild to moderate hypertension. Angiology 1996;47(3):233‐40. - PubMed
Reisin 1997 {published data only}
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    1. Weir MR, Reisin E, Falkner B, Hutchinson HG, Sha L, Tuck ML. Nocturnal reduction of blood pressure and the antihypertensive response to a diuretic or angiotensin converting enzyme inhibitor in obese hypertensive patients. TROPHY study group. American Journal of Hypertension 1998;11(8 Pt 1):914‐20. - PubMed
Russel 1968 {published data only}
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Safar 1994 {published data only}
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Salvetti 1969 {published data only}
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Salvetti 1989 {published data only}
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Samson 1965 {published data only}
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Schaller 1985 {published data only}
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Shahinfar 1999 {published data only}
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Shimizu 1977 {published data only}
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Siegel 1990 {published data only}
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Stein 1992 {published data only}
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Stornello 1990 {published data only}
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TOMHS 1991 {published data only}
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Valmin 1975 {published data only}
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Wassertheil‐Smoller 1992 {published data only}
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Weber 1977 {published data only}
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Webster 1980 {published data only}
    1. Webster J, Dollery CT, Hensby CN. Circulating prostacyclin concentrations may be increased by bendrofluazide in patients with essential hypertension. Clinical Science 1980;59:125‐8S. - PubMed
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Weinberger 1983 {published data only}
    1. Weinberger MH. Influence of an angiotensin converting‐enzyme inhibitor on diuretic‐induced metabolic effects in hypertension. Hypertension 1983;5(5 Suppl III):III132‐III138. - PubMed
Wiggam 1999 {published data only}
    1. Wiggam MI, Bell PM, Sheridan B, Walmsley A, Atkinson AB. Low dose bendrofluazide (1.25 mg) effectively lowers blood pressure over 24 hours. Results of a randomised, double‐blind, placebo‐controlled cross over study. American Journal of Hypertension 1999;12:528‐31. - PubMed
Wilcox 1978 {published data only}
    1. Wilcox RG. Randomised study of six beta‐blockers and a thiazide diuretic in essential hypertension. British Medical Journal 1978;2(6134):383‐5. - PMC - PubMed
Wing 1982 {published data only}
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Wing 1997 {published data only}
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References to other published versions of this review

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