Antihypertensives
| Type | Recommendation |
|---|---|
| When to deprescribe | |
| CBR |
We suggest deprescribing decisions be made in consultation with the person and their GP and/or specialist providers to ensure it aligns with their preferences, goals and overall treatment plans. Following shared decision-making, we suggest deprescribing of antihypertensives be offered to older people with:
|
| Ongoing treatment | |
| CBR |
We suggest continuing antihypertensives in people:
|
| CBR | If deprescribing is unsuccessful despite two attempts, we suggest maintaining the lowest effective dose; however, we suggest reassessing the need for long-term therapy periodically. |
| How to deprescribe | |
| CBR |
We suggest tapering beta blockers and centrally acting antihypertensives (e.g. methyldopa, moxonidine and clonidine) as they are more likely to lead to withdrawal symptoms (e.g. headache, palpitations, and tremors) or rebound hypertension when stopped abruptly. In general, we suggest halving the daily dose every two weeks, ensuring individuals remain symptom-free and SBP < 150 mmHg in people 80 years or above (SBP < 140 mmHg if 75-79 years of age) and DBP < 90 mmHg before initiating each tapering. Once half the lowest standard dose formulation is reached, we suggest discontinuing completely and providing advice on lifestyle changes. For other antihypertensive drug classes, we suggest individualising the need for tapering depending on the drug class and the individual's response and tolerance. |
| CBR | We suggest restarting antihypertensives if SBP is ≥ 150mmHg in people 80 years or above with moderate-to-severe frailty or a history of adverse effects (or SBP ≥ 140 if aged 75-79 years) and DBP is ≥ 90 mm Hg on three consecutive readings over four weeks. If SBP ≥ 180mmHg or DBP ≥ 110mmHg, restart immediately. |
| CBR |
For people taking multiple antihypertensives, we suggest deprescribing one medicine at a time. Priority should be given to antihypertensives with a higher risk of side effects. We suggest the following sequence for deprescribing:
When two antihypertensives have a similar safety profile, the individual's preferences should guide the deprescribing process. |
| Monitoring | |
| CBR |
We suggest advising people to self-monitor for orthostatic symptoms, angina symptoms, blood pressure, and heart rate at home by using a blood pressure monitor if people can use it correctly and to report unusual symptoms to their healthcare provider as needed. We suggest monitoring other drug-specific adverse drug withdrawal events such as palpitations (verapamil, diltiazem, beta-blockers), prostatism (alpha-blockers), or peripheral oedema and shortness of breath (diuretics). |
| CBR |
We suggest closely monitoring for fall risks and ongoing cardiovascular risk factors, at least monthly for the first six months after deprescribing, followed by monitoring every six months thereafter. However, this should be tailored based on individual factors such as their preferences, responses and tolerance to deprescribing. People at a higher risk of cardiovascular risk factors may require more frequent monitoring. We suggest offering advice on lifestyle optimisation for potentially modifiable cardiovascular risk factors. |
CBR, consensus-based recommendation
Note: This section includes evidence from studies that targeted drugs commonly used for hypertension, which includes one or more common drug classes classified under the cardiovascular system. Evidence from studies specifically targeting diuretics is presented separately in the following section.
Hypertension is a common condition among older people that is multifactorial (genetic and environmental) and often contributed to by age-related changes in arterial stiffness (especially systolic hypertension) [307]. Elevated blood pressure (BP) is a well-established risk factor for cardiovascular disease and stroke. Stage 2-3 hypertension, defined as systolic blood pressure (SBP) ≥160 mm Hg or diastolic blood pressure (DBP) ≥100 mm Hg, has been associated with an increased risk of all-cause mortality (hazard ratio [HR] 1.23, 95% confidence interval [CI]: 1.10-1.37) [308]. The primary factor driving the reduction in cardiovascular events in both younger and older people with hypertension is the extent of blood pressure reduction, rather than the specific type of antihypertensives (e.g. ACE inhibitors, beta-blockers, CCBs, or diuretics) [309, 310]. The management of hypertension in older people is particularly complex due to multimorbidity, including frailty, orthostatic hypotension, falls, cognitive impairment, and an increased risk of adverse drug events [311].
Low blood pressure (hypotension) can also lead to significant adverse outcomes. A cohort study found that a substantial proportion of older people on antihypertensives experienced low SBP (< 120 mmHg), which was associated with increased risks of mortality, acute kidney injury, and hospitalisation [312]. Additionally, older people with drug-induced postural hypotension, particularly those at a higher risk of falls, may benefit from deprescribing when the potential harms, such as morbidity from hypotension, outweigh the benefits of reduced cardiovascular events and mortality [313]. Screening for orthostatic hypotension both before and after initiating antihypertensives may be beneficial. BP measurements should be taken while the person is supine and then standing, with a two-minute interval between readings. Orthostatic hypotension is diagnosed when there is a drop of at least 20 mmHg in SBP, a drop of at least 10 mmHg in DBP, or the presence of symptoms such as dizziness, suggesting cerebral hypoperfusion. For postprandial hypotension, screening for symptoms such as weakness, fatigue, or dizziness after meals may be beneficial and confirming these with BP measurements.
Identifying people with pseudohypertension is crucial to prevent overdiagnosis and avoid unnecessary treatment. In some cases, blood pressure may be overestimated in older people due to arterial stiffening or calcification, which increases the cuff pressure required to occlude the artery. This discrepancy between cuff-measured and intra-arterial pressure is referred to as pseudohypertension [314]. Pseudohypertension can lead to overdiagnosis or overtreatment, increasing the risk of adverse effects from unnecessary antihypertensive therapy. While the prevalence of pseudohypertension is unclear, it is known to occur more frequently in people over 65 years of age. In people with resistant or refractory hypertension, pseudohypertension should be considered as a possible cause [315, 316]. A cost-effective screening tool for pseudohypertension is Osler's manoeuver, which involves assessing the palpability of the radial or brachial artery distal to the point of occlusion by the sphygmomanometer cuff. If the artery remains palpable despite the cuff's pressure, the test is considered positive, suggesting the possibility of pseudohypertension. Alternatively, an X-ray of the arteries of the upper limb may assist in confirming the diagnosis [314].
Refer to the narrative evidence summary, the GRADE Summary of Findings table in the guidelines, and the Technical Report for a complete presentation of the deprescribing evidence based on the GRADE framework (including other factors considered in developing the recommendations).
There is currently no consensus among guidelines on the optimal blood pressure target for older people with hypertension. The decision is highly individualised, as the absolute risk reduction depends on a person's baseline cardiovascular risk and their ability to tolerate antihypertensive therapy [311]. A systematic review of guidelines summarised that most guidelines suggest targeting a systolic target of < 150 mmHg, while four other guidelines suggest more intensive treatment with targets below 130 mmHg or even 120 mmHg [317]. For very old and frail people, treatment should align with general guidelines as long as they are able to tolerate antihypertensive therapy. The 2024 European Society of Cardiology Guideline for hypertension management indicates that there is no default need to deprescribe or discontinue antihypertensives in very old and frail people who are tolerating antihypertensives well, but assessment of the appropriateness of therapy should be conducted regularly [318]. The Australian Heart Foundation provides strong recommendations that clinical judgment should guide decisions on the benefit of treatment versus the risk of adverse effects in older people with lower grades of hypertension [319].
Below we summarised the findings from key trials that contributed to the guidelines for hypertension in older people.
As with other health conditions, older people are underrepresented in the majority of hypertension clinical trials. Of the few studies that specifically focused on older people, the 2008 JATOS study evaluated 4,418 people aged 65-84 years, comparing strict BP control (SBP < 140 mmHg) to lenient BP control (SBP 140-160 mmHg) over two years [320]. The study found no significant differences in cardiovascular disease, renal disease, or stroke morbidity and mortality between the two groups with different BP targets.
Similarly, the 2010 VALISH study assessed 3,260 people aged 70-84 years, comparing strict BP control (SBP < 140 mmHg) with moderate BP control (SBP 140-150 mmHg) over a mean follow-up period of 2.85 years [321]. No significant differences were observed in stroke (fatal and non-fatal), myocardial infarction, or all-cause mortality between the two groups.
The HYVET study evaluated 3,845 multi-ethnic people aged 80 years or older with a sustained baseline SBP ≥160 mmHg [322]. The study aimed to achieve a BP goal of < 150/80 mmHg, focusing on fatal or non-fatal stroke as the primary outcome over a median follow-up of 1.8 years. Participants were randomised to receive either indapamide (with or without perindopril) or a matching placebo. With the target BP of 150/80mmHg in the treatment group, there was a significant reduction in death from stroke, all-cause mortality, and the rate of heart failure compared to the control group. However, there was no significant reduction in the rate of fatal or nonfatal stroke or mortality from cardiovascular causes.
A prospective observational study that explored mortality and cardiovascular outcomes in frail individuals aged 75 years or older reported an association between BP below 130/80 mmHg and increased mortality, while an SBP between 140-160 mmHg was correlated with the lowest all-cause mortality [323].
The 2015 SPRINT trial was a landmark RCT that compared intensive blood pressure control (target SBP < 120 mmHg, n=4678) to standard blood pressure control (< 140mmHg, n = 4683) over a median follow-up period of 3 years [324]. In this study, 28% (2636/9361) of participants were aged 75 years or older, with a mean overall age of 68, and with varying levels of frailty. All participants had a baseline SBP of 130 - 180 mmHg, increased cardiovascular risk but without diabetes mellitus or prior stroke. Increased cardiovascular risk was defined as at least one of the following: clinical or subclinical cardiovascular disease other than stroke, chronic kidney disease (excluding polycystic kidney disease) with an estimated glomerular filtration rate (eGFR) of 20 to < 60 mL/min/1.73m2 of body surface area, the 10-year risk of cardiovascular disease of ≥ 15% on the basis of the Framingham risk score or an age of 75 years or older. During the entire follow-up period, the mean SBP for the intensive control group was 122 mmHg, compared to 135 mm Hg in the standard control group. On average, participants in the intensive group used three blood pressure medicines, while those in the standard group used two. The study reported a clear benefit of intensive treatment targets in reducing heart failure, cardiovascular mortality and all-cause mortality. A post-hoc study further reported people with frailty benefited from intensive blood pressure control similar to the overall group when tolerated, without a significant increase in serious adverse events [325]. However, the higher rate of adverse events (serious adverse events of hypotension, syncope, electrolyte abnormalities, and acute kidney injury or failure) in the intensive control group warrants a cautious approach to antihypertensive drug treatment and careful assessment of the severity of frailty. Furthermore, the effects of intensive blood pressure therapy on chronic kidney disease progression were inconclusive due to the small number of renal events, but as mentioned, the intensive-treatment group had more frequent acute kidney injury or acute renal failure than the standard-treatment group [326]. In terms of cognition, intensive BP control was found to significantly reduce the risk of mild cognitive impairment but no significant difference in the risk of probable dementia [327].
Finally, the 2021 STEP trial included over 9,000 people aged 60 to 80 years with hypertension at high risk of cardiovascular events. The trial concluded that compared to standard BP control (target SBP 130-150mmHg), intensive control (target SBP 110-130mmHg) had a lower incidence of stroke, ACS, decompensated heart failure atrial fibrillation, and cardiovascular death. Most adverse events (including dizziness, syncope, fracture, angioedema, headache, cough, and hives) and adverse renal outcomes did not differ significantly between the two groups, except for the incidence of hypotension that was significantly increased in the intensive group (3.4% vs 2.6%; P = 0.03) [328].
To identify individuals who are least likely to derive sufficient net benefit from antihypertensives or tolerate intensive blood pressure control, several factors should be considered. These include age, life expectancy (less than three years), frailty, a high predicted risk of serious adverse events, and a history of adverse events such as falls, syncope, hypotension, or acute kidney injury. Age alone should not be the sole criterion for deprescribing, but it can help identify those more likely to benefit from deprescribing. People over 80 years of age with a SBP < 150 mmHg and DBP < 90 mmHg, and those aged 75 to 79 with a SBP < 140 mmHg, should be carefully assessed for potential risk of adverse outcomes, frailty and a history of adverse events or side effects. To assess frailty, healthcare providers should use validated tools such as the 9-point Clinical Frailty Scale [329]. To effectively assess past adverse events or side effects, obtaining an accurate clinical history is crucial. In addition to a history of falls, syncope, and acute kidney injury, people should also be screened for postural or orthostatic hypotension. Orthostatic hypotension and postprandial hypotension are common side effects of antihypertensive medications, with a prevalence of up to 20% in older people with hypertension [328]. These conditions significantly increase the risk of falls, making early identification essential for adjusting antihypertensive therapy.
Deprescribing may be appropriate when the potential benefits of a medicine are outweighed by the risk of harm. This is particularly relevant when precautions are necessary for continued use or when contraindications are present, as the risk of harm may be inherently higher, especially in older people. The following is a non-exhaustive list of situations where these considerations may apply:
Loop and thiazide diuretics can lead to electrolyte imbalances, exacerbate gout, and may elevate blood glucose levels [330].
Similarly, ACE inhibitors, ARBs, aldosterone antagonists, and potassium-sparing diuretics can raise the risk of hyperkalaemia, particularly in individuals with renal impairment [330].
The combination of an ACE inhibitor and an ARB results in an increased risk of adverse outcomes, including vascular events and renal dysfunction, with limited additional benefit for blood pressure control [331-333].
Nondihydropyridine calcium channel blockers (diltiazem and verapamil) are contraindicated in heart failure with reduced ejection fraction (HFrEF) in the absence of AF due to an associated increase in mortality, unless prescribed under specialist supervision [303, 330]. In people with both AF and HFrEF, these agents are also not recommended, as their negative inotropic effects can worsen heart failure [303, 334].
Use of beta-blockers or verapamil/diltiazem is contraindicated in individuals with inappropriate bradycardia (e.g. resting heart rate < 60 beats/minute) or symptomatic atrioventricular (AV) block (e.g. exertional fatigue) [330].
People aged 85 years or younger who do not meet the criteria for limited life expectancy (less than three years), frailty, a high predicted risk of serious adverse events, and a history of adverse events such as falls, postural hypotension, syncope, or acute kidney injury should generally be managed according to the guidelines for the younger population [318].
Some antihypertensives may be prescribed for comorbid conditions, such as atrial fibrillation, heart failure, or chronic kidney disease. It may not be appropriate to attempt deprescribing in people taking a beta-blocker for atrial fibrillation, a diuretic for symptomatic heart failure, or ACE inhibitors, ARBs, or beta-blockers for heart failure. Similarly, people using ACE inhibitors or ARBs for chronic kidney disease may need to continue taking these medicines for renal protection.
If multiple antihypertensives are considered appropriate to deprescribe, they should be deprescribed one at a time. Some antihypertensives, such as beta-blockers, diuretics, and centrally acting antihypertensives, require tapering due to the risk of rebound hypertension or beta-blocker withdrawal syndrome [293]. Healthcare providers should monitor for withdrawal-related side effects, such as accelerated hypertension (BP > 180/110 mmHg), palpitations (following the withdrawal of verapamil, diltiazem, or beta-blockers), or prostatism (following the withdrawal of alpha-blockers). If these symptoms arise, healthcare providers should consider reintroducing the medicines at a lower dose.
The order to deprescribe should generally prioritise those with a higher risk profile, taking into account any comorbidities and mortality data. In the absence of a specific indication for a particular antihypertensive class (e.g. ACE inhibitors and beta-blockers for heart failure), drugs associated with a higher risk of orthostatic hypotension, such as loop diuretics, alpha-blockers and centrally acting antihypertensives should be prioritised for deprescribing. This is then followed by aldosterone antagonists, thiazide diuretics, and beta-blockers due to the potential to cause fatigue and bradycardia [335]. Calcium channel blockers, ACE inhibitors, and ARBs generally have safer profiles and can be considered last for prioritisation [336].
We identified 20 studies (eight RCTs and 12 single-arm studies) related to antihypertensives deprescribing from the systematic review and meta-analysis, of which two studies specifically targeted beta-blockers and one study targeting ACE inhibitors [317, 337-357].
Overall, the current evidence for deprescribing antihypertensives is derived from studies with outcomes of low and very low certainty. Most studies had a short follow-up duration, either as a run-in phase or short-term withdrawal and most were single-arm observational studies. Deprescribing antihypertensive medicines appeared to result in only a modest increase in BP in most studies; however, a study suggested that BP may revert to baseline in the longer term. Most studies included people without recent cardiovascular events (stroke or myocardial infarction), and SBP < 150-175 mmHg or DBP < 85-110 mmHg. Deprescribing antihypertensives under these situations appears to be largely safe with close monitoring. An association between deprescribing and increased mortality was reported in one retrospective cohort study, also of very low certainty. There is still currently insufficient evidence to support the development of evidence-based recommendations as most studies lack methodological rigor.
Key study characteristics and results
A narrative summary of each study is provided below, highlighting key characteristics and main findings.
Espeland 1999 investigated lifestyle interventions (weight loss and/or sodium restriction) as a replacement for antihypertensives among older people with hypertension in an RCT (TONE trial) [339]. Participants were included if they were taking one antihypertensive (or single combination regimen, diuretic and nondiuretic) with average SBP and DBP < 145 mmHg and 85 mmHg respectively, or able to step down from two antihypertensives to one and meet the BP eligibility criteria. Participants were excluded if they had a history of heart attack or stroke within the past six months, current angina, congestive heart failure, insulin-dependent diabetes or other severe illnesses. Independent of group assignment in the factorial design, 975 participants were randomised, 886 attempted deprescribing and 774 successfully discontinued their antihypertensive. There was a total of 57 cardiovascular events that occurred either during or after drug withdrawal.
Juraschek 2022 conducted a further analysis using the data from the TONE trial to investigate the long-term effects of antihypertensive deprescribing on BP and adverse events independent of group assignment [347]. Following deprescribing, SBP increased by 4.6 mmHg ± 11.1 compared to baseline. There were 113 adverse events affecting 95/975 participants (10%) during deprescribing. Among these adverse events, 84 were symptomatic events (light-headedness, dizziness, vertigo) and 29 were clinical events (falls, fracture, syncope).
Moonen 2015 conducted an RCT (DANTE Study Leiden) to discontinue antihypertensives in older people with SBP of < 160 mmHg and mild cognitive impairment (Mini-Mental State Examination, MMSE score of 21 to 27) [350]. People with dementia, a history of serious cardiovascular events (e.g. stroke, transient ischemic attack), coronary reperfusion procedures, or using antihypertensives for reasons other than hypertension (e.g. arrhythmia, heart failure, angina) were excluded. There was no significant difference in cognition at 16 weeks follow-up between the intervention group and control group who continued taking antihypertensives. Further subgroup analysis (Moonen 2016) including people with orthostatic hypotension (n=162) suggested better recovery from orthostatic hypotension in people who discontinued antihypertensive (RR 1.60, 95% CI 1.10 to 2.31; p = 0.01) as per protocol analyses but this was not statistically significant according to intention-to-treat analysis (RR 1.31, 95% CI 0.92 to 1.87; p = 0.13) [358].
Gulla 2018 conducted a post-hoc analysis focusing on antihypertensives [341] using data from a cluster RCT (COSMOS trial) [135] that investigated the effects of a multicomponent intervention including discontinuation of unnecessary medicines on the quality of life of nursing home residents. There was a significant reduction in the number of hospitalisations in the intervention group participants who received medicine reviews aimed at reducing the use of antihypertensive drugs in nursing homes, compared to control group participants who received usual care (OR 0.38, 95% CI 0.19, 0.76). SBP for those who had their antihypertensives deprescribed increased from a baseline of 128 ± 19.5 mmHg to a mean of 134 mmHg at month nine.
Sheppard 2020 conducted an RCT that included 569 participants with an SBP < 150 mmHg who were taking two or more antihypertensives for 12 months or longer with the goal of reducing medicines in people with polypharmacy and multimorbidity (OPTiMISE trial) [353]. The study excluded people with heart failure due to left ventricular systolic dysfunction or recent myocardial infarction or stroke within the past 12 months. BP monitoring was completed at week 4 and treatment was recommenced if the SBP > 150 mmHg or DBP > 90 mmHg for more than a week. Recommendations were provided to the participant's general practitioner to prioritise deprescribing antihypertensive in reverse of the National Institute for Health and Care Excellence treatment algorithm for people aged over 55 [359]. Participants in the intervention group (n=282) who discontinued one antihypertensive had a 3.4 mmHg (95% CI 1.0, 5.8) higher mean change in SBP compared with the control group receiving usual care (n=287). More participants in the intervention group experienced at least one serious adverse event compared with the continuation group (4.3% vs 2.4% respectively, OR 1.78, 95% CI 0.69, 4.58). Sheppard 2024 further analysed the four-year follow-up outcomes via manual review of the electronic health records for 554 participants (97% of the original sample size) [360]. Of the 213 participants alive in the intervention group, 109 (51%) were still taking fewer antihypertensives than baseline. There was no significant difference between the two groups in the occurrence of all-cause hospitalisation or mortality (OR 0.78, 95% CI 0.54, 1.15).
Song 2018 conducted a retrospective cohort study to investigate antihypertensive deprescribing in nursing home residents with an index fall and SBP between 80 to 120 mmHg [354]. The study compared recurrent falls, hospitalisations, and mortality between the group whose antihypertensive medicines were discontinued (n = 239) versus the group who continued taking antihypertensive (n = 1973) in the 30-day follow-up. There was a significantly higher 30-day mortality rate for the discontinuation group (OR 2.64, 95% CI 1.40, 5.00). However, there were no significant differences between the two groups in recurrent falls (OR 0.89, 95% CI 0.62, 1.26) and hospitalisations (OR 1.41, 95% CI 0.99, 2.02). Further stratification by SBP levels indicated that discontinuing antihypertensives was associated with a statistically significantly lower risk of recurrent falls at 30 days among residents with SBP 80 to 100 mmHg (adjusted marginal effect [AME] = -11.4%; p-value < 0.01) but higher mortality risk among residents with SBP 101 to 120 mmHg (AME = 2.1%; p-value = 0.07).
Hajjar 2013 reported short-term (< four weeks) antihypertensive washout in preparation for trial entry in 53 older people with early cognitive impairment or memory impairment without dementia [342]. Blood pressure increased gradually during the tapering process, with an overall increase of 12 mmHg (95% CI 4, 21) in SBP and 6 mmHg (95% CI 1, 11) in DBP.
Alsop 2001 reported discontinuation of cardiovascular medicines in 65 people attending a falls and syncope clinic [337]. Inclusion and exclusion criteria were not specified. Participants were followed up every two to three months depending on the need for ongoing review. At the end of the 30-month follow-up, cardiovascular medicines remained withdrawn in 70% of participants and 78% reported improved symptoms of syncope or pre-syncope.
Ekbom 1994 reported an observational follow-up of a cohort (n=333) of participants previously taking antihypertensives who entered a wash-out phase prior to participation in the STOP-Hypertension study [338]. Participants were excluded if they were taking these antihypertensives for reasons other than hypertension. At the end of five years of follow-up, approximately one in five (20%) participants remained off anti-hypertensive therapy. Recurrent hypertension (n=54), heart failure (n=27) and oedema (n=25) were the main reasons for restarting therapy. Participants who remained off treatment had a lower total mortality risk than the general Swedish population (matched for age and sex) and a lower risk of cardiovascular events than those receiving treatment (19 deaths reported from 30 expected; P < 0.05). However, it should be underlined that the blood pressure of the participants who remained off treatment did not rise enough to prompt the recommencement of antihypertensives. This suggests the possibility that these participants had an inherently low cardiovascular risk.
Fotherby 1994 reported deprescribing in participants who were taking antihypertensives for more than one year with SBP < 175 mmHg and DBP < 100 mmHg [340]. Participants were excluded if they had recent myocardial infarction, stroke, or symptoms of ischaemic heart disease. At 12 months follow-up, 20/74 (27%) remained normotensive without antihypertensive therapy. Among those who were followed up at two years, 13/64 (20%) were normotensive. The majority of participants who required restarting of therapy did so within the first three months of antihypertensive withdrawal.
Hansen 1983 reported a follow-up study of people who had drug washout in preparation for a study investigating the prevalence of secondary hypertension [355]. The study reported that 43/105 participants (41%) with a history of hypertension remained normotensive without treatment at 11 months follow-up.
Lernfelt 1990 included older people who had a BP of < 175/95 mmHg without current cardiovascular diseases in a cohort study [349]. Antihypertensive was withdrawn in 25 participants. At the final follow-up at month 48, eight participants (32%) remained off their antihypertensive and 13 participants (52%) restarted antihypertensive treatment because of increased BP (n=9), AF and heart failure (n=1), myocardial infarction (n=1), shortness of breath (n=1), or angina (n=1). The remaining four participants (16%) dropped out of the study due to non-cardiovascular reasons.
Nadal 1994 reported an antihypertensive deprescribing before-and-after study in 86 older outpatients attending a hypertension clinic [351]. People were excluded from washout if they had a history of myocardial infarction or stroke in the 12 months prior, insulin-dependent diabetes mellitus, plasma creatinine ≥ 200 mmol/L, and had a SBP ≥ 220 mmHg or DBP ≥ 110 mmHg. Of the 52/86 (60%) participants who remained normotensive after the initial washout, 14/52 (27%) remained without therapy at three years follow-up.
Hassan 2022 investigated deprescribing antihypertensives in older people who used two or more antihypertensives and had at least one adverse drug event (ADE) related to the antihypertensive (dizziness, nocturia, vertigo, headache, imbalance, shortness of breath, and tiredness) [343]. At the end of the 12-month follow-up, antihypertensive drug use was reduced in 11/14 participants (79%). Of these 11 participants, nine (82%) had at least one antihypertensive medicine permanently stopped whereas in two participants (18%), the dose of one antihypertensive drug was halved. All 11 participants had a mean SBP increase of 16 mmHg and a mean DBP increase of eight mmHg. At 12 months follow-up, nine participants (64%) no longer experienced adverse drug events, of whom seven participants had at least one antihypertensive stopped or reduced in dose.
Nelson 2003 conducted a cohort study including 6291 participants who had their antihypertensives discontinued as part of the run-in phase of a larger trial [352]. This study reported that 1228 participants (20%) maintained adequate blood pressure control (mean sitting SBP < 160 mmHg or DBP < 90 mmHg) for 0 to 76 weeks (median of four weeks).
Silva 2024 conducted a subgroup analysis including participants who participated in a larger trial about optimising antihypertensives through seven-day home blood pressure monitoring in older people [357]. The study compared standard care (general practitioner received a home blood pressure monitoring report and decided on deprescribing medications) to study intervention (pharmacist reviews and recommendations). In the intervention group, deprescribing suggestions were provided by the pharmacist to the participants and their general practitioners where appropriate. In the current subgroup study, 72 participants with SBP ≤ 120 mmHg and DBP ≤ 70 mmHg as well as clinical symptoms of hypotension were included (intervention, n = 37; control, n = 35). Compared to control group participants, intervention group participants had a significant reduction in the number of antihypertensives (MD 0.71, 95% CI 0.33, 1.09) on the Day 45 follow-up. Intervention group participants also had a significantly higher in-office SBP (MD 8.06, 95% CI 4.97, 11.15) and DBP (MD 4.49, 95% CI 2.51, 6.47) as well as at-home SBP (MD 7.37, 95% CI 4.42, 10.32) and DBP (MD 4.31, 95% CI 2.53, 6.09). The mean SBP and DBP in the intervention group remained below the target range of 140/90 mmHg after the intervention. There was also a significant reduction in hypotensive symptoms in the intervention group compared with the control group (OR 0.14, 95% CI 0.05, 0.39).
Bogaerts 2024 conducted an RCT trial (DANTON) to investigate the effects of the discontinuation of antihypertensive treatment on neuropsychiatric symptoms and quality of life [356]. Nursing home residents with moderate-to-severe dementia and SBP ≤ 160mmHg were included whereas those with heart failure NYHA-class III to IV, recent cardiovascular events/procedures, or limited life expectancy (< 4 months) were excluded. A total of 205 participants were randomised to discontinuation (n=101) and usual care (n=104). The study was terminated early due to safety concerns and lacking benefits. At the 32-week follow-up, control group participants had fewer neuropsychiatric symptoms measured using the Neuropsychiatric Inventory Nursing Home (NPI-NH) (MD 6.2, 95% CI 1.9, 10.6). However, there was no significant difference between the two groups in terms of quality of life measured using QUALIDEM (MD -3.5, 95%CI -8.1, 1.1), serious adverse events (OR 1.75, 95% CI 0.95, 3.21), mortality (OR 1.71, 95% CI 0.92, 3.18), SBP (MD 4.9, 95% CI -0.8, 10.6), and DBP (MD 3.3, 95% CI -0.5, 7.2).
Additionally, we identified two studies that specifically targeted beta-blockers and one study targeting ACE inhibitors.
Hearing 1999 included 37 participants who were taking atenolol for at least one year in an RCT [344]. The 23 participants who were randomised to the deprescribing group had their atenolol withdrawn over one week of whom eight participants (35%) remained normotensive.
Jondeau 2009 conducted an RCT to determine whether beta-blockers should be discontinued in people hospitalised for acute heart failure with pulmonary oedema [346]. Inclusion criteria include stable doses of beta-blockers for longer than a month, respiratory rate > 24 min-1 during the acute heart failure episode, and left ventricular ejection fraction < 40%. Exclusion criteria were acute ST-elevation myocardial infarction, second or third-degree atrioventricular block, or heart rate lower than 50 min-1. The study found that withholding beta-blockers did not significantly change mortality at month three (OR 0.88, 95% CI 0.27 to 2.85; participants = 147). Participants in the intervention group who stopped beta-blockers at study entry for at least three days were significantly less likely than those in the control group to be taking a beta-blocker at month three (OR 0.38, 95% CI 0.16 to 0.93).
Jiménez-Candil 2005 conducted a before-and-after study to withdraw ACE inhibitors in 20 older people with moderate or severe asymptomatic aortic valve stenosis (considered a relative contraindication to ACE inhibitor therapy) [345]. Participants had previously been taking the ACE inhibitor for at least three months for arterial hypertension. The study found that ACE inhibitor therapy favourably improved stress haemodynamic variables in most hypertensive people with aortic valve stenosis.
Various methods were used for deprescribing in the included studies. Beta-blockers were more commonly tapered gradually, and it may be appropriate to avoid beta-blocker withdrawal syndrome. There was no direct evidence that any particular method was associated with the greatest benefits and harms. However, compared to abrupt cessation, dose tapering is likely more acceptable and helpful in determining the lowest effective dose for some people requiring dose reduction rather than complete cessation.
In one RCT (DANTE Study Leiden), antihypertensives were either abruptly discontinued or tapered within four weeks according to a study-specific algorithm until a maximum increase of 20 mmHg in SBP, or 180 mmHg in SBP was observed (n=356, low certainty) [350]. Atenolol was gradually tapered over one week (study=1, n=37, very low certainty) [344]. In another RCT (n=569), antihypertensive treatment appeared to be discontinued abruptly with the exception of beta-blocker where gradual tapering was encouraged to minimise rebound adrenergic hypersensitivity [353]. Beta-blocker was abruptly discontinued for at least three days in an RCT conducted in a hospital setting (n=169) [346]. The method of deprescribing was not described in four studies (n=1547, very low certainty) [339, 341, 356, 357].
In the single-arm studies, all very low certainty, the method of deprescribing was not described in seven studies (n=2649) [337, 340, 343, 349, 351, 354, 355], the method was individualised following drug-specific tapering regimens (study=1, n=975) [347], beta-blocker was reduced step-wise over a few days (study=1, n=333) [338], step-wise (i.e. one drug at a time, half doses at weekly intervals to the lowest usual therapeutic dose then cease) (study=1, n=6833) [352], antihypertensives were tapered over three weeks (study=1, n=53) [342], and lastly, withdrawal of ACE inhibitor was progressive with a daily dose reduction equivalent to 1.25 mg of enalapril (study=1, n=22) [345].