Article Text

Download PDFPDF
Short-term effect of deprescribing antihypertensives in older people
  1. Franca Morselli1,
  2. Teck K Khong2
  1. 1King's College, London, UK
  2. 2Clinical Pharmacology, St George's University of London, London, UK
  1. Correspondence to Dr Teck K Khong, Clinical Pharmacology, St George's University of London, London SW17 0RE, UK; tkhong{at}


Commentary on: Sheppard JP, Burt J, Lown M, et al. Effect of antihypertensive medication reduction vs usual care on short-term blood pressure control in patients with hypertension aged 80 years and older: The OPTIMISE randomized clinical trial. JAMA. 2020;323:2039–51.

  • Drug-Related Side Effects and Adverse Reactions
  • Health Care Quality, Access, and Evaluation

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Key learning points

  • Although clinical trials have established that treatment of hypertension confers a large benefit in reducing stroke, cardiovascular and all-cause mortality as well as the risk of heart failure in older people, observational studies have also highlighted the potential of harm from low blood pressure and use of multiple antihypertensives.

  • The OPTIMISE trial found that a reduction in the number of antihypertensive medications for 12 weeks in some older people was non-inferior to usual care in terms of rates of control of systolic blood pressure but was associated with the need to reintroduce antihypertensives in almost a quarter of the participants, higher mean BP levels and a greater number of healthcare appointments.

  • This study highlighted the need for more research to establish the longer-term effect of deprescribing antihypertensives in older people including the impact on cardiovascular outcomes, adverse effects and quality of life.


The removal of one antihypertensive drug for 12 weeks in patients aged 80 years or older with a mean blood pressure of approximately 130/69 mm Hg while on a median of two antihypertensives was non-inferior to usual care with regard to rates of control of systolic blood pressure <150 mm Hg but was associated with the requirement to reintroduce medication in approximately 25% of participants, higher mean BP levels and an overall need for more healthcare appointments.1

Study details

The OPTIMISE (Optimising Treatment for Mild Systolic Hypertension in the Elderly) study was a randomised, unblinded, non-inferiority trial that investigated whether a structured approach to reducing antihypertensive treatment for 12 weeks in older people was feasible and did not lead to a clinically significant change in blood pressure control or adverse events.1 Conducted across 69 primary care sites in England, the study recruited people aged ≥80 years with baseline systolic blood pressure <150 mm Hg who were taking two or more antihypertensive medications for at least 12 months. General practitioners were asked to enrol people if they were considered to potentially benefit from medication reduction because of polypharmacy, comorbidity, non-adherence or dislike of medicines, or frailty. People with secondary hypertension or a history of left ventricular dysfunction, myocardial infarction or stroke in the preceding 12 months were excluded. Participants were randomised to the removal of one antihypertensive drug or usual care.

The primary outcome was relative risk (RR) of systolic blood pressure control (defined as <150 mm Hg) between the two groups at 12-week follow-up, with a prespecified non-inferiority margin of 0.9.1 Secondary outcomes were the percentage of participants in the intervention group who adhered to the intervention and between-group differences in frailty, quality of life, adverse effects, serious adverse events, and change in systolic and diastolic blood pressure. The specified sample size (540 participants) was based on the assumption that all those in the usual care group and 96% of those in the intervention group would have systolic blood pressure <150 mm Hg at 12-week follow-up.

Overall, 6194 patients were invited to participate, 739 attended screening and 569 (mean age 85 years, 52% female, 98% ‘white’, mean body mass index 28 kg/m2, mean estimated glomerular filtration rate 61 mL/min/1.73 m2, mean electronic frailty index 0.14) were randomised with 282 allocated to medication reduction and 287 to usual care.1 At baseline, average systolic blood pressure was 130 mm Hg and average diastolic blood pressure was 69 mm Hg (with orthostatic hypotension noted in 5% of individuals) and participants were prescribed a median of two antihypertensives and a total of four medications. For the primary analysis population, participants were analysed according to the group to which they were assigned (265 for the intervention group and 269 for the usual care group). The per-protocol analysis involved 185 people in the intervention group (80 people were excluded from the primary analysis population: 66 people restarted medication and 14 had missing data) and 269 in the usual care group.

For the primary outcome, data from 534 patients at 12 weeks showed that 86% (229/265) in the intervention group and 88% (236/269) in the control group had systolic blood pressure <150 mmHg (adjusted RR 0.98; 97.5% CI 0.92 to ∞; p=0.01).1 The change from baseline in systolic blood pressure was 3.4 mm Hg (95% CI 1.1 to 5.8; p=0.05) higher in the intervention group compared with the usual care group in the primary analysis, and 4.9 mm Hg (95% CI, 2.4 to 7.5; p<0.001) higher in the per-protocol analysis. Diastolic blood pressure was also higher in the intervention group as opposed to the usual care group in both analyses, 2.2 mm Hg (95% CI 0.9 to 3.6; p=0.001) and 3.4 mm Hg (95% CI 1.8 to 4.9; p<0.001), respectively.

In the intervention group, 71% (187/265) maintained the medication reduction and 101 participants (64 people in the per-protocol analysis) had no increase in systolic blood pressure at 12 weeks.1 However, 66 people in the primary analysis group restarted medication. Participants in the intervention group were taking approximately 0.6 fewer antihypertensive medications at 12 weeks, but were found to have attended more healthcare appointments during follow-up (adjusted mean difference 1.24; 95% CI 1.02 to 1.46) and were more likely to experience at least one adverse effect (adjusted RR 1.28; 95% CI 1.06 to 1.54) compared with those in the control group.

The other secondary outcomes of frailty, quality of life, adverse effects and serious adverse events at follow-up did not differ significantly between groups.

Authors’ conclusions

In older patients on multiple antihypertensive drugs, a reduction in antihypertensive medication was non-inferior to usual care, with regard to proportion of patients with a systolic blood pressure<150 mm Hg at 12 weeks. Thus, although further understanding of longer-term outcomes is required, antihypertensive medication reduction can be achieved in some older patients without substantially affecting systolic blood pressure control.


The study was funded by the National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care (NIHR CLAHRC) at Oxford Health NHS Foundation Trust and the NIHR School for Primary Care Research.

Trial registration number

EudraCT database number: 2016-004236-38.

ISRCTN registration number: 97503221.


Hypertension is a major comorbidity in individuals aged ≥85 years, in whom almost 60% are receiving antihypertensive medications.2 Trial data have confirmed that treating hypertension to a level of ≤150/80 mm Hg is associated with large benefit in reduction in stroke, cardiovascular and all-cause mortality as well as heart failure risk in older individuals.3 4 However, observational studies have also highlighted the potential harm of injury from serious falls and increased mortality associated with lower blood pressure and multiple antihypertensive medications.5 6 Accordingly, hypertension guidelines suggest higher threshold and target levels of 150/90 mm Hg specifically for older people, and recommend using clinical judgement for those with frailty and multimorbidity.7 8 Currently, data and guidance on deprescribing antihypertensive medication in older people are limited. In this context, the current trial provides some useful insights into the feasibility and effect of reducing the number of antihypertensive medications taken by older people.

The results of the OPTIMISE trial suggest that deprescribing antihypertensives in older people was not associated with reduced rates of blood pressure control or with adverse effects and serious events. Although these findings provide some reassurance, the trial was short term (lasting only 12 weeks), included highly selected older people without major frailty and who had a relatively low polypharmacy burden comprising a median of two antihypertensives and a total of four medications. Indeed, while it was not possible to determine potential benefits such as improvement in quality of life with deprescribing, the latter was associated with a numerical increase in adverse effects. In addition, mean blood pressure was 3.4/2.2 mm Hg higher in patients randomised to medication reduction compared with usual care, and 4.9/3.4 mm Hg higher in those who maintained reduction in antihypertensive medication. Consequently, it is unclear how findings from this trial might be applied more widely in routine practice or what the impact of wider deprescribing of antihypertensives might have on patients in the longer term.

Finally, it is worth noting that from a total of 69 primary care sites, 6196 patients were invited to participate, 739 screened and 569 recruited; and that among the 282 randomised to medication reduction, reintroduction of antihypertensives was necessary in 66 individuals. Overall, patients in the intervention group received 0.6 fewer antihypertensives at 12 weeks and required more healthcare appointments than those assigned to usual care. Thus, perhaps more than anything else, this trial reminds us that best practice for deprescribing of antihypertensives continues to be uncertain and that in the meantime, deprescribing antihypertensives remains a challenging clinical judgement, and when undertaken, should be managed with careful monitoring and close supervision.

Supplemental material

Supplemental material


Supplementary materials

  • Supplementary Data

    This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.


  • Series co-ordinator Dr Teck Khong, DTB Associate Editor, Clinical Pharmacology, St George’s, University of London, UK

  • Competing interests None declared. Refer to the online supplementary files to view the ICMJE form(s).

  • Provenance and peer review Commissioned; internally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.