Withdrawal of antihypertensive drugs in older people (2024)

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This article is an update of "Withdrawal of antihypertensive drugs in older people" in volume 2017, CD012572.

Background

Hypertension is an important risk factor for subsequent cardiovascular events, including ischaemic and haemorrhagic stroke, myocardial infarction, heart failure, chronic kidney disease, cognitive decline and premature death.Overall, the use of antihypertensive medications has led to reduction in cardiovascular disease, morbidity rates and mortality rates.However, the use of antihypertensive medications is also associated with harms, especially in older people, including the development of adverse drug reactions, drug‐drug interactions and can contribute to increasing medication‐related burden.As such, discontinuation of antihypertensives may be considered and appropriate in some older people.

Objectives

To investigate whether withdrawal of antihypertensive medications is feasible, and evaluate the effects of withdrawal of antihypertensive medications on mortality, cardiovascular outcomes, hypertension and quality of life in older people.

Search methods

The Cochrane Hypertension Information Specialist searched the following databases for randomised controlled trials up to April 2019: the Cochrane Hypertension Specialised Register, CENTRAL (2019, Issue 3), Ovid MEDLINE, Ovid Embase, the WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov. We also conducted reference checking, citation searches and, when appropriate, contacted study authors to identify any additional studies. The searches had no language restrictions.

Selection criteria

We included randomised controlled trials (RCTs) of withdrawal versus continuation of antihypertensive medications used for hypertension or primary prevention of cardiovascular disease in older adults (defined as 50 years and over). Participants were eligible if they lived in the community, residential aged care facilities, or were based in hospital settings. We sought to include trials looking at the complete withdrawal of the antihypertensive medication, and those focusing on a dose reduction of the antihypertensive medicine.

Data collection and analysis

We compared the intervention of discontinuing or reducing antihypertensive medication to usual treatment using mean differences (MD) and 95% confidence intervals (95% CIs) for continuous variables and we used Peto odds ratios (ORs) and 95% CI for binary variables. Our primary outcomes included: mortality, myocardial infarction, development of adverse drug reactions or adverse drug withdrawal reactions.Secondary outcomes included: blood pressure, hospitalisation, stroke, success of withdrawing from antihypertensives, quality of life, and falls.Two authors independently, and in duplicate,conducted all stages of study selection, data extraction and quality assessment.

Main results

Six RCTs met the inclusion criteria and were included in the review (1073 participants). Study duration and follow‐up ranged from 4 weeks to 56 weeks.Meta‐analysis of studies showed that, in the discontinuation group compared to continuation, the odds for all‐cause mortality were 2.08 (95% CI 0.79 to 5.46; low certainty of evidence), for myocardial infarction 1.86 (95% CI 0.19 to 17.98; very low certainty of evidence) and for stroke 1.44 (95% CI 0.25 to 8.35; low certainty of evidence). Blood pressure was higher in the discontinuation group than the continuation group (systolic blood pressure: MD = 9.75 mmHg, 95% CI 7.33 to 12.18; and diastolic blood pressure: MD = 3.5 mmHg, 95% CI 1.82 to 5.18; low certainty of evidence). For the development of adverse events, meta‐analysis was not possible; antihypertensive discontinuation did not appear to increase the risk of adverse events and may lead to resolution of adverse drug reactions, although eligible studies had limited reporting of adverse effects of drug withdrawal (very low certainty of evidence).One study reported hospitalisation with an odds ratio of 0.83 for discontinuation compared to continuation (95% CI 0.33 to 2.10; low certainty of evidence). No studies were identified which reported falls. Between 10.5% and 33.3% of participants in the discontinuation group compared to 9% to 15% in the continuation group experienced raised blood pressure or other clinical criteria (as pre‐defined by the studies) that would require restarting of therapy/removal from the study. The sources of bias included selective reporting (reporting bias), lack of blinding of outcome assessment (detection bias), incomplete outcome data (attrition bias), and lack of blinding of participants and personnel (performance bias).

Authors' conclusions

There is no evidence of an effect of discontinuing compared with continuing antihypertensives used for hypertension or primary prevention of cardiovascular disease in older adults on all‐cause mortality and myocardial infarction. The evidence was low to very low certainty mainly due to small studies and low event rates. These limitations mean that we cannot make any firm conclusions about the effect of deprescribing antihypertensives on these outcomes. Future research should focus on populations with the greatest uncertainty of the benefit:risk ratio for use of antihypertensive medications, such as those with frailty, older age groups and those taking polypharmacy, and measure clinically important outcomes such as falls, quality of life and adverse drug events.

Types of studies

We included randomised controlled trials. All other study types were excluded e.g. observational studies, case series.

Types of participants

Participants were adultsaged 50 years and over prescribed one or more antihypertensive medication(s) for hypertension or primary prevention of cardiovascular disease living in the community, residential aged care facilities or in hospital settings. The cut‐off of 50 years to define ‘older adults’ was chosen to maximise inclusion of relevant older studies and studies from developing countries (Shenkin 2017).

To be eligible, either all participants had to be aged 50 years or older, or results for participants aged 50 years and older had to be presented in a separate subgroup analysis, or the majority of participants had to be 50 years or older (as determined by looking at mean/median age and standard deviation (SD)/interquartile range (IQR) (to be included, the mean age minus the SD must be ≥ 50 years, or if IQR, three‐quarters of participants must be ≥ 50 years old, or the article reported the number of people ≥ 50 years old).

Studies were included if the reported indication in the study was hypertension or primary prevention of cardiovascular disease and less than 20% of the population had cardiovascular disease at baseline.

Types of interventions

Included studies assessed withdrawal of antihypertensive medications in older adults prescribed for hypertension or primary prevention of cardiovascular disease. Withdrawal of medications may be through abrupt withdrawal, tapering to complete withdrawal or dose reduction. The control intervention included no withdrawal of antihypertensive medications (i.e. continuation).

The following antihypertensive medications were included:

• diuretics which act primarily by blocking reabsorption of sodium at four major sites in the nephron. Different classes of diuretics act at different sites. Loop diuretics (e.g. furosemide, torsemide) act in the thick ascending limb of the loop of Henle. Thiazide‐type diuretics (e.g. hydrochlorothiazide, chlorthalidone, indapamide) act in the distal tubule and connecting segment. Potassium‐sparing diuretics (e.g. amiloride, triamterene) increase diuresis, but without causing potassium to be lost from the body. Aldosterone receptor antagonists (e.g. spironolactone, eplerenone) stop the entry of aldosterone into the principal cells of the collecting duct and late distal tubule of the nephron, which prevents sodium and water retention;

• beta‐blockers (e.g. atenolol, carvedilol) block the effects of catecholamines at receptor sites in the heart, peripheral vasculature, bronchi, pancreas, uterus, kidney, brain and liver. Beta‐blockers reduce BP by blocking the effects of catecholamine on the heart and blood vessels;

• ACE inhibitors (e.g. captopril, enalapril) act by blocking the renin‐angiotensin system; specifically, they block conversion of angiotensin I to angiotensin II and bradykinin. ACE inhibitors reduce the effects of angiotensin II‐induced vasoconstriction, sodium retention and aldosterone release;

• calcium channel blockers (e.g. amlodipine, felodipine) act by blocking inward current of calcium via L‐type calcium channels. Calcium channel blockers lower BP by blocking the effects of calcium on blood vessels;

• angiotensin II receptor antagonists (e.g. candesartan, irbesartan) act by blocking binding of angiotensin II to type 1 angiotensin (AT₁) receptors. This leads to reduction in angiotensin II‐induced vasoconstriction, sodium reabsorption and aldosterone release; blood vessels dilate leading to reduction in BP;

• renin inhibitors (e.g. aliskiren) prevent the conversion of angiotensinogen to angiotensin I by binding to the S3^bp binding site of renin.

Types of outcome measures

Electronic searches

The Cochrane Hypertension Information Specialist searched the following databases without language, publication year or publication status restrictions:

• the Cochrane Hypertension Specialised Register via the Cochrane Register of Studies (CRS‐Web) (searched 22 May 2019);

• the Cochrane Central Register of Controlled Trials (CENTRAL, 2019, Issue 3) via the Cochrane Register of Studies (CRS‐Web) (searched 22 April 2019);

• MEDLINE Ovid (from 1946 onwards), MEDLINE Ovid Epub Ahead of Print, and MEDLINE Ovid In‐Process & Other Non‐Indexed Citations (searched 22 April 2019);

• Embase Ovid (from 1974 onwards) (searched 22 April 2019);

• ClinicalTrials.gov (www.clinicaltrials.gov) (searched 22 April 2019);

• World Health Organisation International Clinical Trials Registry Platform (http:// https://apps.who.int/trialsearch) (searched 22 April 2019).

The Information Specialist modelled subject strategies for databases on the search strategy designed for MEDLINE. Where appropriate, they were combined with subject strategy adaptations of the highly sensitivity and precision‐maximising search strategy designed by Cochrane for identifying randomised controlled trials (as described in the Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0, Box 6.4.d. (Higgins 2011)). We present search strategies for major databases in Appendix 1.

Searching other resources

The Cochrane Hypertension Information Specialist searched the Hypertension Specialised Register segment (which includes searches of MEDLINE and Embase) for systematic reviews and Epistemonikos to retrieve published systematic reviews related to this review title to identify additional relevant trials. The Cochrane Hypertension Information Specialist searched the Hypertension Specialised Register segment for information of adverse effects relevant to this review.

We checked the bibliographies of included studies and any relevant systematic reviews identified for further references to relevant trials.

We contacted experts/organisations in the field to obtain additional information on relevant trials.

We contacted trial authors for clarification and further data if trial reports were unclear.

Selection of studies

Two review authors (out of ER, WT, MS, AT, TM, IH, VJ, and DG)independentlyconducted article screeningfor relevance and adherence to inclusion criteria. If studies did not meet the inclusion criteria, we excluded them and recorded reasons for exclusion. Disagreements were resolved through consultation with a third review author.

Data extraction and management

Two review authors(out of ER, WT, MS, AT, and DG) independentlyperformeddata extraction. Disagreements were resolved by consultation with a third review author.

The summary statistics required for each trial and outcome for continuous data included the values at different time points, mean change from baseline or difference between intervention and control group, the standard deviation and the number of participants in each group (discontinuation and continuation). The baseline assessments were defined as the latest available assessment between the discontinuation and continuation group, or from baseline. For binary outcomes (e.g. success rate), the number and percentage in (each) group were sought.

We extracted the following data from the studies and presented them in a summary table:

• author, year of publication, country;

• type of intervention;

• antihypertensive medication withdrawn;

• withdrawal method (immediate or tapered);

For each outcome measure, we extracted data as per the primary analysis presented in each of the studies.

Assessment of risk of bias in included studies

Two review authors (out of ER, WT, MS, AD, and DG)independently assessed the risk of bias in the included studies using the guidelines in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011; Sterne 2014). Weassessed the risk of bias in terms of internal validity criteria for RCTs including random sequence generation (randomisation), allocation concealment, participant and study personnel blinding, blinding of outcome assessors, level of incomplete outcome data, selective reporting and other risks of bias that may be relevant (Higgins 2011; Sterne 2014). Disagreements were resolved through consultation with a third review author, when necessary.

Measures of treatment effect

Studies may or may not utilise similar rating scales in outcome assessment. For this reason, for continuous outcomes, we used the mean difference (MD) when the collective studies utilised identical scales of rating or tests. We planned to use the standardised mean difference (SMD) if dissimilar scales of rates or tests were used. In the case of binary outcomes such as mortality, we used a Peto odds ratios (ORs) to measure the treatment effect. We also calculated 95% confidence intervals (Cls).

Unit of analysis issues

If there were any cluster RCTs, we planned to determine if the risk of unit of analysis error was dealt with appropriately. Where the analysis was carried out correctly taking into account the clustering design, we planned to consider the studies for meta‐analysis and use the reported effect sizes and standard errors. Where the analysis was incorrect (i.e. not taking the clustering design into account), we planned to apply an interclass correlation (Higgins 2011). However, no cluster RCTs were found.

Dealing with missing data

We contacted the corresponding author of included studies in the event of missing data that would compromise the ability of the review authors to examine the data and eligibility for study exclusion/inclusion in the final analysis.

Assessment of heterogeneity

We performed meta‐analysis where studies were satisfactorily hom*ogenous in terms of interventions, outcomes and participants. In the evaluation of heterogeneity, we determined clinical heterogeneity by review author opinion and used an I² test to determine statistical heterogeneity. An I² value higher than 50% was considered as evidence for the presence of substantial heterogeneity of the studies. If substantial heterogeneity was present, we aimed to investigate the reasons for the presence of heterogeneity through subgroup analysis.

Assessment of reporting biases

Two review authors (out of ER, DG, MS, AT, and WT) independently assessed the risk of reporting bias in the included studies following the guidelines in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). We resolved disagreements through consultation with a third review author.

Data synthesis

We synthesiseddata for each study outcome separately using Review Manager 5 (RevMan 2014), and we undertook meta‐analyses for outcomes reported in multiple studies.

We compared outcome measures for binary data utilising Peto odds ratios, due to the rare nature of the primary outcomes, and 95% CI. This necessitated the use of the fixed effect model. For continuous variables or data, we utilised mean differences and 95% CI.

Subgroup analysis and investigation of heterogeneity

Where there were two or more studies, we performed subgroup analysis of medications within antihypertensive medication classes (e.g. ACE inhibitors and diuretics) and based on duration of follow‐up (less than 12 months versus 12 months or longer) if sufficient and meaningful data were available. We used class of medication and duration of follow‐up subgroups when investigating heterogeneity. Additionally, we intended to conduct subgroups analyses for age group (50 to 65 years, over 65 to 80 years, over 80 years) and gender (men and women). However, this was not possible as data were not reported separately for these groups.

Sensitivity analysis

We intended to perform sensitivity analysis to consider how the results of any meta‐analyses undertaken changed under different assumptions, related to the reasons for these effects. More specifically, we intended to conduct a sensitivity analysis on the choice of utilising a random‐effects model (Higgins 2011). However, we were unable to perform any sensitivity analyses due to the limited data and small number of studies identified.

Summary of findings and assessment of the certainty of the evidence

We used the GRADE approach to assess the certainty of the evidence for each outcome (Schünemann 2011a; Schünemann 2011b). We present key findings of the review, including a summary of the data, the magnitude of the effect size and the overall certainty of the evidence, in Table 1. We preselected the following outcomes for inclusion in the Table 1: mortality, myocardial infarction, adverse drug reactions, blood pressure (systolic and diastolic), hospitalisation, stroke and incidence of falls.

1

Results of the search

A total of 3677 articles were identified. After de‐duplication, title and abstract screening, a total of 39 studies were obtained in full text (Figure 1). We excluded 33 articles (Characteristics of excluded studies). No additional eligible studies were found through hand searching of reference lists.

Included studies

Six studies fulfilled the inclusion criteria, comprising 1073 participants (Characteristics of included studies). Two studies were conducted in the USA (Langford 1984;Maland 1983), two in the Netherlands (Moonen 2015; Walma 1997), one in Canada (Myers 1982) and one in Wales (Burr 1977).

Excluded studies

We excluded 33 publications (reasons for exclusion are shown in Characteristics of excluded studies). Reasons for exclusion were wrong intervention (participants were not randomised to withdraw or continue antihypertensives or withdrawal was temporary); wrong patient population (not older adults or wrong indication); wrong study design (not an RCT); one or both groups had confounding treatment (such as additional dietary or exercise intervention or other antihypertensives); clinical trial registry citation of an ineligible study due to wrong patient population; and a protocol paper of an ineligible study due to wrong intervention.

Allocation

All studies were assessed as having low or unclear risk of selection bias. Two studies reported appropriate methods of random sequence generation and were assessed as low risk in this domain (Moonen 2015; Walma 1997). Three studies had a low risk of bias in the allocation concealment domain; Myers 1982 and Walma 1997 used hospital pharmacists to ensure allocation concealment while Moonen 2015 noted a centralised computer randomisation procedure. The majority of studies had an unclear risk of selection bias due to insufficient information.

Blinding

Four of the studies were assessed as having low risk of bias in the blinding of participants and personnel domain as they reported that the study was double‐blind and also described some method of blinding, such as using identical placebos for the withdrawal group (Burr 1977; Maland 1983; Myers 1982; Walma 1997). Burr 1977 also noted that the containers were special so as to ensure that personnel were blinded to allocation. Of these four studies, two (Maland 1983; Myers 1982) had insufficient details about blinding of assessors (unclear risk of bias) and one (Walma 1997) was assessed as having low risk of detection bias as it reported that allocation codes were not broken until assessment of the last data had been completed.

The trial by Moonen 2015 did not blind the participants and physicians to treatment group, however, the research personal assessing the outcomes were masked to allocation group. Finally, Langford 1984 didn't specify whether blinding was conducted; external physicians could restart the medication, therefore it is unlikely to have been blinded. As restarting the medication was the primary outcome, this study was assessed as having high risk of performance and detection bias.

Incomplete outcome data

Three studies were assessed as having low risk of attrition bias (Maland 1983; Moonen 2015; Walma 1997), one was unclear (Langford 1984) and the remaining two were high risk (Burr 1977; Myers 1982). Burr 1977 had unclear reporting of dropouts and inconsistent reporting of outcomes particularly for the continuation group, while in the study by Myers 1982, there were uneven dropout rates (with different reasons for dropouts between the groups) and incomplete data reported on their main outcome (BP).

Selective reporting

Only one study was assessed as having low risk of reporting bias (Walma 1997), with the others being unclear (Burr 1977; Myers 1982) or at high risk of bias (Langford 1984; Maland 1983; Moonen 2015). Two studies were assessed as at high risk of bias as outcomes appeared to be reported in unclear and/or select ways with grouping of participants not as per the originally allocated groups (Langford 1984; Maland 1983). For example, Maland 1983 reported BP results for 'reverters' (those whose BP increased to a level requiring restarting of treatment) separately to other participants in the withdrawal group. The third study assessed as being at high risk of reporting bias reported an outcome in their protocol (attached as supplementary data) which was not reported in the main manuscript (Moonen 2015).

Other potential sources of bias

No other potential sources of bias were identified in the studies.

Primary outcomes

Secondary outcomes

The findings of this review have clinical implications for the management of hypertension in older adults, and could be considered in the next updates of international guidelines. For example, the 2017 American College of Cardiology/American Heart Association (ACC/AHA) guidelines (Whelton 2018) did not comment on withdrawal of antihypertensives beyond perioperative recommendations, although they do provide information on the risks of abrupt cessation of beta‐blockers and clonidine (physiological adverse drug withdrawal reactions). The 2018 European Society of Cardiology/European Society of Hypertension (ESC/ESH) guidelines (Williams 2018) stated, ‘Withdrawal of BP‐lowering drug treatment on the basis of age, even when patients attain an age of ≥ 80 years, is not recommended, provided that treatment is well tolerated’. It also commented that ‘it is well established that BP‐lowering treatment withdrawal leads to a marked increase in CV disease’, based on a subgroup analysis of the HYVET trial, which was designed to investigate treatment versus placebo rather than withdrawal of treatment. Our systematic review of deprescribing trials did not confirm this risk. Future iterations of treatment guidelines could consider also including data from deprescribing trials synthesised in our review.

The limitations of the available data on deprescribing of antihypertensives, as described in the discussion, restrict their impact on current practice. There is a paucity of high certainty evidence applicable to current practice and to the situations in which deprescribing is often considered clinically (frailty, falls, dementia, polypharmacy), and an absence of data on key outcomes important to older adults, such as falls and quality of life. The variability in the populations and inclusion/exclusion criteria of the included studies mean that we can not make recommendations as to which individuals should have their antihypertensive medication deprescribed, or a BP cut‐point at which deprescribing should occur. However, the feasibility of withdrawal and the lack of a significant increase in mortality, CVD or stroke in meta‐analysis, may help clinicians when considering deprescribing antihypertensives and discussing this with patients, particularly in those who are at high risk of harm, such as those with frailty, falls, dementia and polypharmacy. Shared decision‐making, specification of patient‐specific goals (such as reversal of side effects or reduction of pill burden) and close monitoring of the effects in the individual remain pillars of clinical practice when deprescribing antihypertensives (Scott 2019).

The current state of evidence on antihypertensive discontinuation reveals several areas of focus for future research. More RCTs will help to further establish the potential benefit and safety of antihypertensive withdrawal, particularly in populations where there is uncertainty in the net benefit of treatment. Future RCTs would ideally be powered to detect differences in clinically meaningful outcomes such as cardiovascular events or mortality. These RCTs could also focus on evaluating the comparative effects of discontinuing different medication classes. For example, investigating whether there are differences in clinical outcomes, rates of withdrawal symptoms, and success rate between different medications or medication classes. Since the context for discontinuation may be different in certain populations (e.g. frail older person with multiple comorbidities versus low‐risk younger old), it will also be helpful for future studies to examine whether differences in the potential benefit and safety of antihypertensive discontinuation exist between specific populations. It will also be useful for future studies to clearly describe their discontinuation plan (e.g. tapering rate and duration), such that discontinuation protocols can be replicated in other studies and/or more easily implemented in practice. Since risk of future cardiovascular events is of particular interest with respect to antihypertensive discontinuation, it will also be helpful for future studies to gather longer‐term outcome data (12 months or beyond). This would serve to more clearly elucidate the downstream effects of antihypertensive discontinuation on cardiovascular events or mortality. Continuing to follow‐up participants who have restarted the medication due to predefined BP or clinical criteria would provide important information for shared decision‐making. Further, since return of underlying symptoms or adverse drug withdrawal events are also particularly relevant for antihypertensive discontinuation, future RCTs should include robust measures to capture this to provide a better picture of the safety of discontinuation. Finally, future studies should focus on evaluating patient‐centred outcomes such as quality of life and falls.

In broader terms, this review highlights the need for more research into the benefits and harms of deprescribing specific medication classes to provide evidence to guide clinical decision‐making and inform clinical practice guidelines. It will also be important to consider whether large RCTs are the best study design for this research question and the role of large observational database studies to inform decision‐making. Additionally, as identified in ours and previous reviews (Froom 1997; Iyer 2008), identifying deprescribing studies for systematic reviews can be challenging due to the wide variety of terminology in this space. Development of a standardised search strategy and recommendations for keyword referencing for all new studies in the field is likely to improve the ability to identify and synthesise evidence about deprescribing. The need for further research and synthesis of deprescribing research aligns with the internationally recognised problem of medical excess, such as overdiagnosis, overtreatment, and unnecessary testing (Johansson 2019).

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Appendix 1. Search strategies

Database: Ovid MEDLINE(R) and Epub Ahead of Print, In‐Process & Other Non‐Indexed Citations, Daily and Versions(R) <1946 to April 19, 2019>
Search Date: 22 April 2019
‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐
1 exp aged/
2 middle aged/
3 (advanced years or ageing or aging or elder$ or elderly or frail or geriatric? or gerontolog$ or later life or middle aged or midlife or nursing care or nursing home? or old age or oldest old or pensioner? or post‐menopausal or postmenopausal or senior or seniors).mp.
4 (old$ adj3 (adult? or female? or male? or men or people or person or women)).tw,kf.
5 ((over or older) adj2 ("49" or "50" or "51" or "52" or "53" or "54" or "55" or "56" or "57" or "58" or "59" or "60" or "61" or "62" or "63" or "64" or "65" or "66" or "67" or "68" or "69" or "70" or "71" or "72" or "73" or "74" or "75" or "76" or "77" or "78" or "79" or "80" or "81" or "82" or "83" or "84" or "85" or "86" or "87" or "88" or "89" or "90" or "91" or "92" or "93" or "94" or "95" or "96" or "97" or "98" or "99" or "100") adj years).tw.
6 (aged or aging or ageing or elder$ or geriatric$ or gerontolog$).jw,nw.
7 or/1‐6
8 hypertension/
9 essential hypertension/
10 (antihypertens$ or hypertens$).tw,kf.
11 ((elevat$ or high$ or raised) adj2 (bp or blood pressure)).tw,kf.
12 or/8‐11
13 exp antihypertensive agents/
14 exp thiazides/
15 exp sodium chloride symporter inhibitors/
16 exp sodium potassium chloride symporter inhibitors/
17 ((ceiling or loop) adj diuretic?).tw,kf.
18 (amiloride or benzothiadiazine or bendroflumethiazide or bumetanide or chlorothiazide or cyclopenthiazide or furosemide or hydrochlorothiazide or hydroflumethiazide or methyclothiazide or metolazone or polythiazide or trichlormethiazide or veratide or thiazide?).tw,kf.
19 (chlorthalidone or chlortalidone or phthalamudine or chlorphthalidolone or oxodoline or thalitone or hygroton or indapamide or metindamide).tw,kf.
20 or/14‐19
21 exp angiotensin‐converting enzyme inhibitors/
22 angiotensin converting enzyme inhibit$.tw,kf.
23 (ace adj2 inhibit$).tw,kf.
24 acei.tw,kf.
25 (alacepril or altiopril or ancovenin or benazepril or captopril or ceranapril or ceronapril or cilazapril or deacetylalacepril or delapril or derapril or enalapril or epicaptopril or fasidotril or fosinopril or foroxymithine or gemopatrilat or idapril or imidapril or indolapril or libenzapril or lisinopril or moexipril or moveltipril or omapatrilat or pentopril$ or perindopril$ or pivopril or quinapril$ or ramipril$ or rentiapril or saralasin or s nitrosocaptopril or spirapril$ or temocapril$ or teprotide or trandolapril$ or utibapril$ or zabicipril$ or zofenopril$ or Aceon or Accupril or Altace or Capoten or Lotensin or Mavik or Monopril or Prinivil or Univas or Vasotec or Zestril).tw,kf.
26 or/21‐25
27 exp Angiotensin Receptor Antagonists/
28 (angiotensin adj3 receptor antagon$).tw,kf.
29 (angiotensin adj3 receptor block$).tw,kf.
30 (arb or arbs).tw,kf.
31 (abitesartan or azilsartan or candesartan or elisartan or embusartan or eprosartan or forasartan or irbesartan or losartan or milfasartan or olmesartan or saprisartan or tasosartan or telmisartan or valsartan or zolasartan or Atacand or Avapro or Benicar or Cozaar or Diovan or Micardis or Teveten).tw,kf.
32 or/27‐31
33 exp calcium channel blockers/
34 (amlodipine or aranidipine or barnidipine or bencyclane or benidipine or bepridil or cilnidipine or cinnarizine or clentiazem or darodipine or diltiazem or efonidipine or elgodipine or etafenone or fantofarone or felodipine or fendiline or flunarizine or gallopamil or isradipine or lacidipine or lercanidipine or lidoflazine or lomerizine or manidipine or mibefradil or nicardipine or nifedipine or niguldipine or nilvadipine or nimodipine or nisoldipine or nitrendipine or perhexiline or prenylamine or semotiadil or terodiline or tiapamil or verapamil or Cardizem CD or Dilacor XR or Tiazac or Cardizem Calan or Isoptin or Calan SR or Isoptin SR Coer or Covera HS or Verelan PM).tw,kf.
35 (calcium adj2 (antagonist? or block$ or inhibit$)).tw,kf.
36 or/33‐35
37 (methyldopa or alphamethyldopa or amodopa or dopamet or dopegyt or dopegit or dopegite or emdopa or hyperpax or hyperpaxa or methylpropionic acid or dopergit or meldopa or methyldopate or medopa or medomet or sembrina or aldomet or aldometil or aldomin or hydopa or methyldihydroxyphenylalanine or methyl dopa or mulfasin or presinol or presolisin or sedometil or sembrina or taquinil or dihydroxyphenylalanine or methylphenylalanine or methylalanine or alpha methyl dopa).mp.
38 (reserpine or serpentina or rauwolfia or serpasil).mp.
39 (clonidine or adesipress or arkamin or caprysin or catapres$ or catasan or chlofazolin or chlophazolin or clinidine or clofelin$ or clofenil or clomidine or clondine or clonistada or clonnirit or clophelin$ or dichlorophenylaminoimidazoline or dixarit or duraclon or gemiton or haemiton or hemiton or imidazoline or isoglaucon or klofelin or klofenil or m‐5041t or normopresan or paracefan or st‐155 or st 155 or tesno timelets).mp.
40 exp hydralazine/
41 (hydralazin$ or hydrallazin$ or hydralizine or hydrazinophtalazine or hydrazinophthalazine or hydrazinophtalizine or dralzine or hydralacin or hydrolazine or hypophthalin or hypoftalin or hydrazinophthalazine or idralazina or 1‐hydrazinophthalazine or apressin or nepresol or apressoline or apresoline or apresolin or alphapress or alazine or idralazina or lopress or plethorit or praeparat).tw,kf.
42 or/37‐41
43 exp adrenergic beta‐antagonists/
44 (acebutolol or adimolol or afurolol or alprenolol or amosulalol or arotinolol or atenolol or befunolol or betaxolol or bevantolol or bisoprolol or bopindolol or bornaprolol or brefonalol or bucindolol or bucumolol or bufetolol or bufuralol or bunitrolol or bunolol or bupranolol or butofilolol or butoxamine or carazolol or carteolol or carvedilol or celiprolol or cetamolol or chlortalidone cloranolol or cyanoiodopindolol or cyanopindolol or deacetylmetipranolol or diacetolol or dihydroalprenolol or dilevalol or epanolol or esmolol or exaprolol or falintolol or flestolol or flusoxolol or hydroxybenzylpinodolol or hydroxycarteolol or hydroxymetoprolol or indenolol or iodocyanopindolol or iodopindolol or iprocrolol or isoxaprolol or labetalol or landiolol or levobunolol or levomoprolol or medroxalol or mepindolol or methylthiopropranolol or metipranolol or metoprolol or moprolol or nadolol or oxprenolol or penbutolol or pindolol or nadolol or nebivolol or nifenalol or nipradilol or oxprenolol or pafenolol or pamatolol or penbutolol or pindolol or practolol or primidolol or prizidilol or procinolol or pronetalol or propranolol or proxodolol or ridazolol or salcardolol or soquinolol or sotalol or spirendolol or talinolol or tertatolol or tienoxolol or tilisolol or timolol or tolamolol or toliprolol or tribendilol or xibenolol).tw,kf.
45 (beta adj2 (adrenergic? or antagonist? or block$ or receptor?)).tw,kf.
46 or/43‐45
47 exp adrenergic alpha antagonists/
48 (alfuzosin or bunazosin or doxazosin or metazosin or neldazosin or prazosin or silodosin or tamsulosin or terazosin or tiodazosin or trimazosin).tw,kf.
49 (adrenergic adj2 (alpha or antagonist?)).tw,kf.
50 ((adrenergic or alpha or receptor?) adj2 block$).tw,kf.
51 or/47‐50
52 13 or 20 or 26 or 32 or 36 or 42 or 46 or 51
53 withdraw$.tw,kf.
54 (ceased or ceasing or cessation$).tw,kf.
55 (deprescrib$ or discontinu$).tw,kf.
56 ((reduced or reduces or reducing or reduction?) adj4 (antihypertens$ or anti‐hypertens$ or dosage? or dose or doses or drug$ or medicat$ or prescri$)).tw,kf.
57 stop$.tw,kf.
58 taper$.tw,kf.
59 or/53‐58
60 randomized controlled trial.pt.
61 controlled clinical trial.pt.
62 randomized.ab.
63 placebo.ab.
64 clinical trials as topic/
65 randomly.ab.
66 trial.ti.
67 or/60‐66
68 animals/ not (humans/ and animals/)
69 Pregnancy/ or Hypertension, Pregnancy‐Induced/ or Pregnancy Complications, Cardiovascular/ or exp Ocular Hypertension/
70 (pregnancy‐induced or ocular hypertens$ or preeclampsia or pre‐eclampsia).ti.
71 67 not (68 or 69 or 70) (
72 7 and 12 and 52 and 59 and 71
‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐
Database: Cochrane Hypertension Specialised Register via Cochrane Register of Studies
Search Date: 22 May 2019
‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐
#1 (ageing OR aging OR elder* OR frail OR geriatric* OR middle aged OR nursing care OR nursing home* OR old age OR older OR pensioner* OR postmenopausal OR post‐menopausal OR senior OR seniors) AND INREGISTER
#2 ((49 OR 50 OR 51 OR 52 OR 53 OR 54 OR 55 OR 56 OR 57 OR 58 OR 59 OR 60 OR 61 OR 62 OR 63 OR 64 OR 65 OR 66 OR 67 OR 68 OR 69 OR 70 OR 71 OR 72 OR 73 OR 74 OR 75 OR 76 OR 77 OR 78 OR 79 OR 80 OR 81 OR 82 OR 83 OR 84 OR 85 OR 86 OR 87 OR 88 OR 89 OR 90 OR 91 OR 92 OR 93 OR 94 OR 95 OR 96 OR 97 OR 98 OR 99 OR 100) NEXT years) AND INREGISTER
#3 (#1 OR #2) AND INSEGMENT
#4 (antihypertens* OR hypertens* OR elevated blood pressure OR high* blood pressure OR raised blood pressure) AND INREGISTER
#5 (ceased OR ceasing OR cessation OR deprescrib* OR discontinu* OR stop* OR taper* OR withdraw*) AND INREGISTER
#6 RCT: DE AND INREGISTER
#7 Review:ODE AND INREGISTER
#8 (#6 OR #7) AND INREGISTER
#9 (#3 AND #4 AND #5 AND #8) AND INREGISTER
‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐
Database: Cochrane Central Register of Controlled Trials (CENTRAL) via Cochrane Register of Studies
Search Date: 22 April 2019
‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐
#1 (ageing OR aging OR elder* OR frail OR geriatric* OR middle aged OR nursing care OR nursing home* OR old age OR older OR pensioner* OR postmenopausal OR post‐menopausal OR senior OR seniors) AND CENTRAL:TARGET
#2 ((49 OR 50 OR 51 OR 52 OR 53 OR 54 OR 55 OR 56 OR 57 OR 58 OR 59 OR 60 OR 61 OR 62 OR 63 OR 64 OR 65 OR 66 OR 67 OR 68 OR 69 OR 70 OR 71 OR 72 OR 73 OR 74 OR 75 OR 76 OR 77 OR 78 OR 79 OR 80 OR 81 OR 82 OR 83 OR 84 OR 85 OR 86 OR 87 OR 88 OR 89 OR 90 OR 91 OR 92 OR 93 OR 94 OR 95 OR 96 OR 97 OR 98 OR 99 OR 100) NEXT years) AND CENTRAL:TARGET
#3 (#1 OR #2) AND CENTRAL:TARGET
#4 (antihypertens* OR hypertens* OR elevated blood pressure OR high* blood pressure OR raised blood pressure) AND CENTRAL:TARGET
#5 (ceased OR ceasing OR cessation OR deprescrib* OR discontinu* OR stop* OR taper* OR withdraw*) AND CENTRAL:TARGET
#6 (#3 AND #4 AND #5) AND CENTRAL:TARGET
#7 #6 AND INREGISTER:TARGET
#8 #6 NOT #7 AND CENTRAL:TARGET
‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐
Database: Embase <1974 to 2019 April 19>
Search Date: 22 April 2019
‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐
1 exp aged/
2 middle aged/
3 (advanced years or ageing or aging or elder$ or elderly or frail or geriatric? or gerontolog$ or later life or middle aged or midlife or nursing care or nursing home? or old age or oldest old or pensioner? or post‐menopausal or postmenopausal or senior or seniors).mp.
4 (old$ adj3 (adult? or female? or male? or men or people or person or women)).tw.
5 ((over or older) adj2 ("49" or "50" or "51" or "52" or "53" or "54" or "55" or "56" or "57" or "58" or "59" or "60" or "61" or "62" or "63" or "64" or "65" or "66" or "67" or "68" or "69" or "70" or "71" or "72" or "73" or "74" or "75" or "76" or "77" or "78" or "79" or "80" or "81" or "82" or "83" or "84" or "85" or "86" or "87" or "88" or "89" or "90" or "91" or "92" or "93" or "94" or "95" or "96" or "97" or "98" or "99" or "100") adj years).tw.
6 (aged or aging or ageing or elder$ or geriatric$ or gerontolog$).jw,nw.
7 or/1‐6
8 exp hypertension/
9 (antihypertens$ or hypertens$).tw.
10 ((elevat$ or high$ or raised) adj2 (bp or blood pressure)).tw.
11 or/8‐10
12 exp antihypertensive agent/
13 exp thiazide diuretic agent/
14 exp loop diuretic agent/
15 ((ceiling or loop) adj diuretic?).tw.
16 (amiloride or benzothiadiazine or bendroflumethiazide or bumetanide or chlorothiazide or cyclopenthiazide or furosemide or hydrochlorothiazide or hydroflumethiazide or methyclothiazide or metolazone or polythiazide or trichlormethiazide or veratide or thiazide?).tw.
17 (chlorthalidone or chlortalidone or phthalamudine or chlorphthalidolone or oxodoline or thalitone or hygroton or indapamide or metindamide).tw.
18 or/13‐17
19 exp dipeptidyl carboxypeptidase inhibitor/
20 angiotensin converting enzyme inhibit$.tw.
21 (ace adj2 inhibit$).tw.
22 acei.tw.
23 (alacepril or altiopril or ancovenin or benazepril or captopril or ceranapril or ceronapril or cilazapril or deacetylalacepril or delapril or derapril or enalapril or epicaptopril or fasidotril or fosinopril or foroxymithine or gemopatrilat or idapril or imidapril or indolapril or libenzapril or lisinopril or moexipril or moveltipril or omapatrilat or pentopril$ or perindopril$ or pivopril or quinapril$ or ramipril$ or rentiapril or saralasin or s nitrosocaptopril or spirapril$ or temocapril$ or teprotide or trandolapril$ or utibapril$ or zabicipril$ or zofenopril$ or Aceon or Accupril or Altace or Capoten or Lotensin or Mavik or Monopril or Prinivil or Univas or Vasotec or Zestril).tw.
24 or/19‐23
25 exp angiotensin receptor antagonist/
26 (angiotensin adj3 receptor antagon$).tw.
27 (angiotensin adj3 receptor block$).tw.
28 (arb or arbs).tw.
29 (abitesartan or azilsartan or candesartan or elisartan or embusartan or eprosartan or forasartan or irbesartan or losartan or milfasartan or olmesartan or saprisartan or tasosartan or telmisartan or valsartan or zolasartan or Atacand or Avapro or Benicar or Cozaar or Diovan or Micardis or Teveten).tw.
30 or/25‐29
31 exp calcium channel blocking agent/
32 (amlodipine or aranidipine or barnidipine or bencyclane or benidipine or bepridil or cilnidipine or cinnarizine or clentiazem or darodipine or diltiazem or efonidipine or elgodipine or etafenone or fantofarone or felodipine or fendiline or flunarizine or gallopamil or isradipine or lacidipine or lercanidipine or lidoflazine or lomerizine or manidipine or mibefradil or nicardipine or nifedipine or niguldipine or nilvadipine or nimodipine or nisoldipine or nitrendipine or perhexiline or prenylamine or semotiadil or terodiline or tiapamil or verapamil or Cardizem CD or Dilacor XR or Tiazac or Cardizem Calan or Isoptin or Calan SR or Isoptin SR Coer or Covera HS or Verelan PM).tw.
33 (calcium adj2 (antagonist? or block$ or inhibit$)).tw.
34 or/31‐33
35 (methyldopa or alphamethyldopa or amodopa or dopamet or dopegyt or dopegit or dopegite or emdopa or hyperpax or hyperpaxa or methylpropionic acid or dopergit or meldopa or methyldopate or medopa or medomet or sembrina or aldomet or aldometil or aldomin or hydopa or methyldihydroxyphenylalanine or methyl dopa or mulfasin or presinol or presolisin or sedometil or sembrina or taquinil or dihydroxyphenylalanine or methylphenylalanine or methylalanine or alpha methyl dopa).mp.
36 (reserpine or serpentina or rauwolfia or serpasil).mp.
37 (clonidine or adesipress or arkamin or caprysin or catapres$ or catasan or chlofazolin or chlophazolin or clinidine or clofelin$ or clofenil or clomidine or clondine or clonistada or clonnirit or clophelin$ or dichlorophenylaminoimidazoline or dixarit or duraclon or gemiton or haemiton or hemiton or imidazoline or isoglaucon or klofelin or klofenil or m‐5041t or normopresan or paracefan or st‐155 or st 155 or tesno timelets).mp.
38 (hydralazin$ or hydrallazin$ or hydralizine or hydrazinophtalazine or hydrazinophthalazine or hydrazinophtalizine or dralzine or hydralacin or hydrolazine or hypophthalin or hypoftalin or hydrazinophthalazine or idralazina or 1‐hydrazinophthalazine or apressin or nepresol or apressoline or apresoline or apresolin or alphapress or alazine or idralazina or lopress or plethorit or praeparat).tw.
39 or/35‐38
40 exp beta adrenergic receptor blocking agent/
41 (acebutolol or adimolol or afurolol or alprenolol or amosulalol or arotinolol or atenolol or befunolol or betaxolol or bevantolol or bisoprolol or bopindolol or bornaprolol or brefonalol or bucindolol or bucumolol or bufetolol or bufuralol or bunitrolol or bunolol or bupranolol or butofilolol or butoxamine or carazolol or carteolol or carvedilol or celiprolol or cetamolol or chlortalidone cloranolol or cyanoiodopindolol or cyanopindolol or deacetylmetipranolol or diacetolol or dihydroalprenolol or dilevalol or epanolol or esmolol or exaprolol or falintolol or flestolol or flusoxolol or hydroxybenzylpinodolol or hydroxycarteolol or hydroxymetoprolol or indenolol or iodocyanopindolol or iodopindolol or iprocrolol or isoxaprolol or labetalol or landiolol or levobunolol or levomoprolol or medroxalol or mepindolol or methylthiopropranolol or metipranolol or metoprolol or moprolol or nadolol or oxprenolol or penbutolol or pindolol or nadolol or nebivolol or nifenalol or nipradilol or oxprenolol or pafenolol or pamatolol or penbutolol or pindolol or practolol or primidolol or prizidilol or procinolol or pronetalol or propranolol or proxodolol or ridazolol or salcardolol or soquinolol or sotalol or spirendolol or talinolol or tertatolol or tienoxolol or tilisolol or timolol or tolamolol or toliprolol or tribendilol or xibenolol).tw.
42 (beta adj2 (adrenergic? or antagonist? or block$ or receptor?)).tw.
43 or/40‐42
44 exp alpha adrenergic receptor blocking agent/
45 (alfuzosin or bunazosin or doxazosin or metazosin or neldazosin or prazosin or silodosin or tamsulosin or terazosin or tiodazosin or trimazosin).tw.
46 (adrenergic adj2 (alpha or antagonist?)).tw.
47 ((adrenergic or alpha or receptor?) adj2 block$).tw.
48 or/44‐47
49 12 or 18 or 24 or 30 or 34 or 39 or 43 or 48
50 withdraw$.tw.
51 (ceased or ceasing or cessation$).tw.
52 (deprescrib$ or discontinu$).tw.
53 ((reduced or reduces or reducing or reduction?) adj4 (antihypertens$ or anti‐hypertens$ or dosage? or dose or doses or drug$ or medicat$ or prescri$)).tw.
54 stop$.tw.
55 taper$.tw.
56 or/50‐55
57 randomized controlled trial/
58 crossover procedure/
59 double‐blind procedure/
60 (randomi?ed or randomly).tw.
61 (crossover$ or cross‐over$).tw.
62 placebo.ab.
63 (doubl$ adj blind$).tw.
64 assign$.ab.
65 allocat$.ab.
66 or/57‐65
67 (exp animal/ or animal.hw. or nonhuman/) not (exp human/ or human cell/ or (human or humans).ti.)
68 exp pregnancy/ or maternal hypertension.mp. or exp pregnancy complication/ or intraocular hypertension/
69 (pregnancy‐induced or ocular hypertens$ or preeclampsia or pre‐eclampsia).ti.
70 66 not (67 or 68 or 69)
71 7 and 11 and 49 and 56 and 70
‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐
Database: ClinicalTrials.gov
Search Date: 22 April 2019
‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐
Condition or disease: Hypertension
Other terms: randomized
Study Type: Interventional Studies (Clinical Trials)
Intervention/treatment: ceased OR ceasing OR cessation OR deprescrib* OR discontinu* OR stop* OR taper* OR withdrawal
‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐
Database: WHO International Clinical Trials Registry Platform (ICTRP)
Search Date: 22 April 2019
‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐
hypertens* AND elder* AND randomized AND ceased
hypertens* AND older AND randomized AND ceased
hypertens* AND elder* AND randomized AND ceasing
hypertens* AND older AND randomized AND ceasing
hypertens* AND elder* AND randomized AND cessation
hypertens* AND older AND randomized AND cessation
hypertens* AND elder* AND randomized AND deprescrib*
hypertens* AND older AND randomized AND deprescrib*
hypertens* AND elder* AND randomized AND discontinu*
hypertens* AND older AND randomized AND discontinu*
hypertens* AND elder* AND randomized AND stop*
hypertens* AND older AND randomized AND stop*
hypertens* AND elder* AND randomized AND taper*
hypertens* AND older AND randomized AND taper*
hypertens* AND aged AND randomized AND withdraw*
hypertens* AND elder* AND randomized AND withdraw*
hypertens* AND older AND randomized AND withdraw*
hypertens* AND elder* and randomized
‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐
Database: Epistemonikos
Search Date: 22 April 2019
‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐
(title:(hypertens* OR elevated blood pressure OR high blood pressure) OR abstract:(hypertens* OR elevated blood pressure OR high blood pressure)) AND (title:(advanced years OR ageing OR aging OR elder* OR elderly OR frail OR geriatric* OR gerontology* OR later life OR middle aged OR nursing care OR nursing home* OR old age OR oldest old OR pensioner* OR post‐menopausal OR postmenopausal OR senior OR seniors) OR abstract:(advanced years OR ageing OR aging OR elder* OR elderly OR frail OR geriatric* OR gerontology* OR later life OR middle aged OR nursing care OR nursing home* OR old age OR oldest old OR pensioner* OR post‐menopausal OR postmenopausal OR senior OR seniors))
AND
Publication type: Systematic Review

Discontinuation by no treatment/placebo of antihypertensives vs Continuation

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