Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

ACC 2024 Congress

Catch up on all the top stories and latest evidence in cardiology research with our ACC 2024 Congress hub page.
ADVANCED SEARCH
Log in
Top
BMC Geriatrics
Published in: BMC Geriatrics 1/2017

Open Access 01-10-2017 | Systematic Review

Thiazides in the management of hypertension in older adults – a systematic review

Authors: Christina Sommerauer, Neha Kaushik, Adrine Woodham, Anna Renom-Guiteras, Yolanda V Martinez, David Reeves, Ilkka Kunnamo, Thekraiat Al Qur‵an, Steffen Hübner, Andreas Sönnichsen

Published in: BMC Geriatrics | Special Issue 1/2017

Login to get access

Abstract

Background

Thiazides are commonly prescribed to older people for the management of hypertension. The objective of this study was to identify the evidence on the risks and benefits of their use among adults aged ≥65 years and to develop recommendations to reduce potentially inappropriate use.

Methods

Systematic review (SR) of the literature covering six databases. We applied a staged search approach, where each search was undertaken only if the previous one did not yield high quality results. Searches 1 and 2 identified relevant SRs and meta-analyses published up to December 2015 from all databases. Search 3 identified additional individual interventional studies (IS) and observational studies (OS) not identified by the preceding searches. We included all studies evaluating the effect of thiazides on patient-relevant outcomes in the management of hypertension with a sufficient number of participants aged ≥65 years or a subgroup analysis based on age. Two independent reviewers extracted data and carried out quality appraisal. Recommendations were developed using the GRADE methodology.

Results

Searches 1 to 3 were performed. We included 34 articles reporting on 12 IS and 4 OS. Mean ages ranged from 59 to 83.8 years. Four studies had performed a subgroup analysis by age. Information on comorbidity, polypharmacy and frailty of the participants was scarce or not available. The IS compared thiazides to placebo or other antihypertensive drugs and evaluated cardiovascular endpoints or all-cause-mortality as primary outcomes. The OS investigated the association between thiazide use and the risk of gout, fractures and adverse effects. Our results suggest that thiazides are efficacious in preventing cardiovascular events for this population group. Low-dose regimens of thiazides may be safer than high-dose (low quality of evidence), and a history of gout may increase the risk of adverse events (low quality of evidence). Three recommendations were developed.

Conclusions

The use of low dose treatment with thiazides for the management of hypertension in adults aged 65 and older seems justified, unless a history of gout is present. The quality of the evidence is low and studies rarely describe characteristics of the participants such as polypharmacy and frailty. Further good quality studies are needed.
Appendix
Available only for authorised users
Literature
1.
Lloyd-Jones DM, Evans JC, Levy D. Hypertension in adults across the age spectrum: current outcomes and control in the community. JAMA. 2005;294(4):466–72.CrossRefPubMed
2.
Musini VM, Tejani AM, Bassett K, Wright JM. Pharmacotherapy for hypertension in the elderly. Cochrane Database of Systematic Reviews 2010;(12).
3.
Benetos A, Rossignol P, Cherubini A, Joly L, Grodzicki T, Rajkumar C, Strandberg TE, Petrovic M. Polypharmacy in the aging patient: Management of Hypertension in octogenarians. JAMA. 2015;314(2):170–80.CrossRefPubMed
4.
Mancia G, Fagard R, Narkiewicz K, Redon J, Zanchetti A, Bohm M, Christiaens T, Cifkova R, De Backer G, Dominiczak A, et al. 2013 ESH/ESC 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). Eur Heart J. 2013;34(28):2159–219.CrossRefPubMed
5.
James PA, Oparil S, Carter BL, Cushman WC, Dennison-Himmelfarb C, Handler J, Lackland DT, LeFevre ML, MacKenzie TD, Ogedegbe O, 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(5):507–20.CrossRefPubMed
6.
Agarwal R. Treating hypertension in hemodialysis improves symptoms seemingly unrelated to volume excess. Nephrol Dial Transplant. 2016;31(1):142–9.CrossRefPubMed
7.
8.
Nickel CH, Ruedinger JM, Messmer AS, Maile S, Peng A, Bodmer M, Kressig RW, Kraehenbuehl S, Bingisser R. Drug-related emergency department visits by elderly patients presenting with non-specific complaints. Scand J Trauma Resusc Emerg Med. 2013;21:15.CrossRefPubMedPubMedCentral
9.
Gallagher P, Ryan C, Byrne S, Kennedy J, O'Mahony D. STOPP (screening tool of older Person's prescriptions) and START (screening tool to alert doctors to right treatment). Consensus validation. Int J Clin Pharmacol Ther. 2008;46(2):72–83.CrossRefPubMed
10.
Boyd CM, Darer J, Boult C, Fried LP, Boult L, Wu AW. Clinical practice guidelines and quality of care for older patients with multiple comorbid diseases: implications for pay for performance. JAMA. 2005;294(6):716–24.CrossRefPubMed
11.
Sonnichsen A, Trampisch US, Rieckert A, Piccoliori G, Vogele A, Flamm M, Johansson T, Esmail A, Reeves D, Loffler C, et al. Polypharmacy in chronic diseases-reduction of inappropriate medication and adverse drug events in older populations by electronic decision support (PRIMA-eDS): study protocol for a randomized controlled trial. Trials. 2016;17:57.CrossRefPubMedPubMedCentral
12.
13.
Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JP, Clarke M, Devereaux PJ, Kleijnen J, Moher D. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. PLoS Med. 2009;6(7):e1000100.CrossRefPubMedPubMedCentral
14.
Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6(7):e1000097.CrossRefPubMedPubMedCentral
15.
Shea BJ, Grimshaw JM, Wells GA, Boers M, Andersson N, Hamel C, Porter AC, Tugwell P, Moher D, Bouter LM. Development of AMSTAR: a measurement tool to assess the methodological quality of systematic reviews. BMC Med Res Methodol. 2007;7:10.CrossRefPubMedPubMedCentral
16.
Shea BJ, Hamel C, Wells GA, Bouter LM, Kristjansson E, Grimshaw J, Henry DA, Boers M. AMSTAR is a reliable and valid measurement tool to assess the methodological quality of systematic reviews. J Clin Epidemiol. 2009;62(10):1013–20.CrossRefPubMed
17.
Programme CAS: 11 questions to help you make sens of case control study. 2013.
18.
Programme CAS: 12 questions to help you make sense of cohort study. 2013.
19.
Guyatt GH, Oxman AD, Kunz R, Falck-Ytter Y, Vist GE, Liberati A, Schunemann HJ. Going from evidence to recommendations. BMJ (Clinical research ed). 2008;336(7652):1049–51.CrossRef
20.
Guyatt GH, Oxman AD, Kunz R, Vist GE, Falck-Ytter Y, Schunemann HJ. What is "quality of evidence" and why is it important to clinicians? BMJ (Clinical research ed). 2008;336(7651):995–8.CrossRef
21.
Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck-Ytter Y, Alonso-Coello P, Schunemann HJ. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ (Clinical research ed). 2008;336(7650):924–6.CrossRef
22.
Qaseem A, Snow V, Owens DK, Shekelle P. The development of clinical practice guidelines and guidance statements of the American College of Physicians: summary of methods. Ann Intern Med. 2010;153(3):194–9.CrossRefPubMed
23.
Kunnamo I: Methodology handbook for EBM guidelines, its evidence summaries, and EBMeDS decision support rules. 2016.
24.
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(23):2981–997.
25.
ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major cardiovascular events in hypertensive patients randomized to doxazosin vs chlorthalidone: the antihypertensive and lipidlowering treatment to prevent heart attack trial (ALLHAT). ALLHAT Collaborative Research Group. JAMA. 2000;283(15):1967–975.
26.
ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Diuretic versus alphablocker as first-step antihypertensive therapy: final results from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Hypertension. 2003;42(3):239–46.
27.
Barzilay JI, Davis BR, Bettencourt J, Margolis KL, Goff DC Jr, Black H, Habib G, Ellsworth A, Force RW, Wiegmann T, et al. Cardiovascular outcomes using doxazosin vs. chlorthalidone for the treatment of hypertension in older adults with and without glucose disorders: a report from the ALLHAT study. J Clin Hypertens (Greenwich). 2004;6(3):116–25.CrossRef
28.
Chalmers J, Castaigne A, Morgan T, Chastang C. Long-term efficacy of a new, fixed, very-low-dose angiotensin-converting enzyme-inhibitor/diuretic combination as first-line therapy in elderly hypertensive patients. J Hypertens. 2000;18(3):327–37.CrossRefPubMed
29.
Dhalla IA, Gomes T, Yao Z, Nagge J, Persaud N, Hellings C, Mamdani MM, Juurlink DN. Chlorthalidone versus hydrochlorothiazide for the treatment of hypertension in older adults: a population-based cohort study. Ann Intern Med. 2013;158(6):447–55.CrossRefPubMed
30.
Amery A, Birkenhager W, Brixko R, Bulpitt C, Clement D, Deruyttere M, De Schaepdryver A, Dollery C, Fagard R, Forette F, et al. Efficacy of antihypertensive drug treatment according to age, sex, blood pressure, and previous cardiovascular disease in patients over the age of 60. Lancet (London, England). 1986;2(8507):589–92.CrossRef
31.
Amery A, Birkenhager W, Brixko P, Bulpitt C, Clement D, Deruyttere M, De Schaepdryver A, Dollery C, Fagard R, Forette F, et al. Mortality and morbidity results from the European working party on high blood pressure in the elderly trial. Lancet (London, England). 1985;1(8442):1349–54.CrossRef
32.
Fletcher AE. Adverse treatment effects in the trial of the European working party on high blood pressure in the elderly. Am J Med. 1991;90(3A):42S–4S.CrossRefPubMed
33.
Staessen J, Bulpitt C, Clement D, De Leeuw P, Fagard R, Fletcher A, Forette F, Leonetti G, Nissinen A, O'Malley K, et al. Relation between mortality and treated blood pressure in elderly patients with hypertension: report of the European working party on high blood pressure in the elderly. BMJ. 1989;298(6687):1552–6.CrossRefPubMedPubMedCentral
34.
Staessen J. Mortality and treated blood pressure in patients of the European working party on high blood pressure in the elderly. Am J Med. 1991;90(suppl 3A):3A–S.
35.
Gurwitz JH, Kalish SC, Bohn RL, Glynn RJ, Monane M, Mogun H, Avorn J. Thiazide diuretics and the initiation of anti-gout therapy. J Clin Epidemiol. 1997;50(8):953–9.CrossRefPubMed
36.
Effect of antihypertensive treatment on stroke recurrence. Hypertension-stroke cooperative study group. JAMA. 1974, 229(4):409–418.
37.
Beckett NS, Peters R, Fletcher AE, Staessen JA, Liu L, Dumitrascu D, Stoyanovsky V, Antikainen RL, Nikitin Y, Anderson C, et al. Treatment of hypertension in patients 80 years of age or older. N Engl J Med. 2008;358(18):1887–98.CrossRefPubMed
38.
Peters R, Beckett N, Forette F, Tuomilehto J, Clarke R, Ritchie C, Waldman A, Walton I, Poulter R, Ma S, et al. Incident dementia and blood pressure lowering in the hypertension in the very elderly trial cognitive function assessment (HYVET-COG): a double-blind, placebo controlled trial. Lancet Neurol. 2008;7(8):683–9.CrossRefPubMed
39.
Bulpitt CJ, Beckett NS, Cooke J, Dumitrascu DL, Gil-Extremera B, Nachev C, Nunes M, Peters R, Staessen JA, Thijs L. Results of the pilot study for the hypertension in the very elderly trial. J Hypertens. 2003;21(12):2409–17.CrossRefPubMed
40.
Jamerson K, Weber MA, Bakris GL, Dahlof B, Pitt B, Shi V, Hester A, Gupte J, Gatlin M, Velazquez EJ. Benazepril plus amlodipine or hydrochlorothiazide for hypertension in high-risk patients. N Engl J Med. 2008;359(23):2417–28.CrossRefPubMed
41.
Kuramoto K, Matsushita S, Kuwajima I, Murakami M. Prospective study on the treatment of mild hypertension in the aged. Jpn Heart J. 1981;22(1):75–85.CrossRefPubMed
42.
LaCroix AZ, Wienpahl J, White LR, Wallace RB, Scherr PA, George LK, Cornoni-Huntley J, Ostfeld AM. Thiazide diuretic agents and the incidence of hip fracture. N Engl J Med. 1990;322(5):286–90.CrossRefPubMed
43.
Malacco E, Mancia G, Rappelli A, Menotti A, Zuccaro MS, Coppini A. Treatment of isolated systolic hypertension: the SHELL study results. Blood Press. 2003;12(3):160–7.CrossRefPubMed
44.
MRC Working Party. Medical Research Council trial of treatment of hypertension in older adults: principal results. BMJ. 1992;304(6824):405–12.
45.
Bird AS, Blizard RA, Mann AH. Treating hypertension in the older person: an evaluation of the association of blood pressure level and its reduction with cognitive performance. J Hypertens. 1990;8(2):147–52.CrossRefPubMed
46.
Hulley SB, Furberg CD, Gurland B, McDonald R, Perry HM, Schnaper HW, Schoenberger JA, Smith WM, Vogt TM. Systolic hypertension in the elderly program (SHEP): antihypertensive efficacy of chlorthalidone. Am J Cardiol. 1985;56(15):913–20.CrossRefPubMed
47.
Perry HM Jr, McDonald RH, Hulley SB, Smith WM, Furberg CD, Greenlick MR, Kuller LH, Schnaper HW, Schoenberger JA, Vogt TM. Systolic hypertension in the elderly program, pilot study (SHEP-PS): morbidity and mortality experience. J Hypertens z. 1986;4(6):S21–3.
48.
Perry HM Jr, Smith WM, McDonald RH, Black D, Cutler JA, Furberg CD, Greenlick MR, Kuller LH, Schnaper HW, Schoenberger JA, et al. Morbidity and mortality in the systolic hypertension in the elderly program (SHEP) pilot study. Stroke. 1989;20(1):4–13.CrossRefPubMed
49.
SHEP Cooperative Research Group. Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). JAMA. 1991;265(24):3255–264.
50.
Hawkins CM. Isolated systolic hypertension, morbidity, and mortality: the SHEP experience. Am J Geriatr Cardiol. 1993;2(5):25–7.PubMed
51.
Perry HM Jr, Davis BR, Price TR, Applegate WB, Fields WS, Guralnik JM, Kuller L, Pressel S, Stamler J, Probstfield JL. Effect of treating isolated systolic hypertension on the risk of developing various types and subtypes of stroke: the systolic hypertension in the elderly program (SHEP). JAMA. 2000;284(4):465–71.CrossRefPubMed
52.
Kostis JB, Davis BR, Cutler J, Grimm RH Jr, Berge KG, Cohen JD, Lacy CR, Perry HM Jr, Blaufox MD, Wassertheil-Smoller S, et al. Prevention of heart failure by antihypertensive drug treatment in older persons with isolated systolic hypertension. SHEP cooperative research group. JAMA. 1997;278(3):212–6.CrossRefPubMed
53.
Curb JD, Pressel SL, Cutler JA, Savage PJ, Applegate WB, Black H, Camel G, Davis BR, Frost PH, Gonzalez N, et al. Effect of diuretic-based antihypertensive treatment on cardiovascular disease risk in older diabetic patients with isolated systolic hypertension. Systolic hypertension in the elderly program cooperative research group. JAMA. 1996;276(23):1886–92.CrossRefPubMed
54.
Savage PJ, Pressel SL, Curb JD, Schron EB, Applegate WB, Black HR, Cohen J, Davis BR, Frost P, Smith W, 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.CrossRefPubMed
55.
Somes GW, Pahor M, Shorr RI, Cushman WC, Applegate WB. The role of diastolic blood pressure when treating isolated systolic hypertension. Arch Intern Med. 1999;159(17):2004–9.CrossRefPubMed
56.
Weiland S, R A, Keil U, Lewis M, Dennler H-J, Welzel D. Thiazide diuretics and the risk of hip fracture among 70-79 year old woman treated for hypertension. Eur J Pub Health. 1997;7(3):335–40.CrossRef
57.
Staessen J. The determinants and prognostic significance of serum uric acid in elderly patients of the European working party on high blood pressure in the elderly trial. Am J Med. 1991;90(3A):50S–4S.PubMed
58.
Wright JM, Lee CH, Chambers GK. Systematic review of antihypertensive therapies: does the evidence assist in choosing a first-line drug? CMAJ. 1999;161(1):25–32.PubMedPubMedCentral
59.
Khanna D, Fitzgerald JD, Khanna PP, Bae S, Singh MK, Neogi T, Pillinger MH, Merill J, Lee S, Prakash S, et al. 2012 American College of Rheumatology guidelines for management of gout. Part 1: systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia. Arthritis Care Res (Hoboken). 2012;64(10):1431–46.CrossRef
60.
Cauley JA, Cummings SR, Seeley DG, Black D, Browner W, Kuller LH, Nevitt MC. Effects of thiazide diuretic therapy on bone mass, fractures, and falls. The study of osteoporotic fractures research group. Ann Intern Med. 1993;118(9):666–73.CrossRefPubMed
61.
Heidrich FE, Stergachis A, Gross KM. Diuretic drug use and the risk for hip fracture. Ann Intern Med. 1991;115(1):1–6.CrossRefPubMed
62.
Herings RM, Stricker BH, de Boer A, Bakker A, Sturmans F, Stergachis A. Current use of thiazide diuretics and prevention of femur fractures. J Clin Epidemiol. 1996;49(1):115–9.CrossRefPubMed
63.
Wright JM, Musini VM. First-line drugs for hypertension. Cochrane Database Syst Rev. 2009;3:CD001841.
64.
Kongkaew C, Hann M, Mandal J, Williams SD, Metcalfe D, Noyce PR, Ashcroft DM. Risk factors for hospital admissions associated with adverse drug events. Pharmacotherapy. 2013;33(8):827–37.CrossRefPubMed
65.
Neff KM, Nawarskas JJ. Hydrochlorothiazide versus chlorthalidone in the management of hypertension. Cardiol Rev. 2010;18(1):51–6.CrossRefPubMed
66.
Dorsch MP, Gillespie BW, Erickson SR, Bleske BE, Weder AB. Chlorthalidone reduces cardiovascular events compared with hydrochlorothiazide: a retrospective cohort analysis. Hypertension. 2011;57(4):689–94.CrossRefPubMed
67.
Roush GC, Holford TR, Guddati AK. Chlorthalidone compared with hydrochlorothiazide in reducing cardiovascular events: systematic review and network meta-analyses. Hypertension. 2012;59(6):1110–7.CrossRefPubMed
68.
Barat I, Andreasen F, Damsgaard EM. The consumption of drugs by 75-year-old individuals living in their own homes. Eur J Clin Pharmacol. 2000;56(6–7):501–9.CrossRefPubMed
69.
Glaeske G. S C: BARMER GEK Arzneimittelreport 2013.
Metadata
Title
Thiazides in the management of hypertension in older adults – a systematic review
Authors
Christina Sommerauer
Neha Kaushik
Adrine Woodham
Anna Renom-Guiteras
Yolanda V Martinez
David Reeves
Ilkka Kunnamo
Thekraiat Al Qur‵an
Steffen Hübner
Andreas Sönnichsen
Publication date
01-10-2017
Publisher
BioMed Central
Published in
BMC Geriatrics / Issue Special Issue 1/2017
Electronic ISSN: 1471-2318
DOI
https://doi.org/10.1186/s12877-017-0576-3

Other articles of this Special Issue 1/2017

BMC Geriatrics 1/2017 Go to the issue

Systematic Review

Effectiveness and safety of beta blockers in the management of hypertension in older adults: a systematic review to help reduce inappropriate prescribing

Systematic Review

Effectiveness and patient safety of platelet aggregation inhibitors in the prevention of cardiovascular disease and ischemic stroke in older adults – a systematic review

Systematic Review

Efficacy and safety of metformin in the management of type 2 diabetes mellitus in older adults: a systematic review for the development of recommendations to reduce potentially inappropriate prescribing

Systematic Review

Effectiveness and safety of vitamin K antagonists and new anticoagulants in the prevention of thromboembolism in atrial fibrillation in older adults – a systematic review of reviews and the development of recommendations to reduce inappropriate prescribing

Study protocol

A set of systematic reviews to help reduce inappropriate prescribing to older people: study protocol

Systematic Review

Effectiveness and safety of dipeptidyl peptidase 4 inhibitors in the management of type 2 diabetes in older adults: a systematic review and development of recommendations to reduce inappropriate prescribing

ACC 2024 Congress Coverage

Cardiology Video

Highlights from the ACC 2024 Congress

Watch now

Watch official videos from the ACC congress summarizing key highlights from the last year in heart failure, cardiomyopathies, valvular disease, pulmonary vascular disease, and pediatric cardiology.

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits