Deprescribing antihypertensive medication in frail older adults: balancing the complexities of polypharmacy and individualised care

Key Points

• Editorial to accompany: Effects of the discontinuation of antihypertensive treatment on neuropsychiatric symptoms and quality of life in nursing home residents with dementia (DANTON): a multicentre, open-label, blinded-outcome, randomised controlled trial [10]

• Deprescribing preventive mediation requires a balanced perspective on the uncertainties and complexities

• Deprescribing antihypertensive therapy in patients with dementia can be indicated despite a lack of positive effect on behaviour,

• Deprescribing requires a process of advance care planning and shared decision-making with the patient or their caregiver

• RCTs on deprescribing in a population without adverse effects of studied medication have little chance of a positive outcome

Managing polypharmacy in frail older adults is a complex and demanding task for healthcare providers. As individuals age, they often develop multiple chronic conditions and acquire risk factors for acute events such as stroke and myocardial infarction. This multimorbidity significantly affects daily functioning and independence. Rendering preventive pharmacotherapeutic treatment increasingly important. Since the risk for (especially cardiovascular) serious events in most cases will increase with age, the oldest old may even benefit more from secondary prevention efforts than younger persons. It is therefore not surprising that medication use and thus the prevalence of polypharmacy in the oldest old is growing [1].

But indicated polypharmacy also has potential downsides. In the oldest old it is associated with a heightened risk of adverse drug events and mortality [2–4]. Increased pharmacodynamic sensitivity, pharmacokinetic drug–drug interactions and cumulative pharmacodynamic effects, such as multiple drugs affecting blood pressure regulation or the combined use of psychotropics, may elevate the risk of severe side effects, like falls, sedation, cognitive impairment and incontinence.

Another point to consider is that treatment goals may shift as patients age [5]. In end-of-life care or with progressive, debilitating conditions like dementia, patients and caregivers may prioritise quality of life (QoL) today over life extension. In such situations, the appropriateness of once indicated preventive therapies such as antihypertensive treatment (AHT), may be questioned [6].

The changed risk–benefit balance and shifted treatment goals are significant drivers of deprescribing amongst clinicians in geriatric care [7–9]. However, data on the effects of deprescribing preventive medications in frail older persons remain limited. How can we determine whether a patient will benefit from continuing or discontinuing a particular medication?

In this journal, the results of the Discontinuation of Antihypertensive Treatment in Older People with Dementia Living in a Nursing Home (DANTON) Study are presented. This open-label, blinded-outcome Randomized Controlled Trial (RCT) examined whether discontinuing AHT could reduce neuropsychiatric symptoms (NPS) and enhance QoL [10]. Unfortunately, the study was terminated early following a recommendation from the Data Safety Monitoring Board, with only 194 out of the planned 492 participants enrolled. Interim analysis suggested that the study was unlikely to yield positive effects on co-primary outcomes, with an observed increase in serious adverse events (SAEs). At 16 weeks, no significant differences in NPS or QoL were observed between the groups. SAEs occurred in 36% of the discontinuation group and 24% of the usual care group, with 32-week outcomes favouring usual care. The authors concluded that ‘discontinuation of AHT in this context does not appear to be either safe or beneficial enough to be recommended in older adults with dementia’.

If the term ‘this context’ refers to the outcomes ‘neuropsychiatric functioning’ or QoL, this conclusion is understandable. Studies suggest a beneficial effect of AHT discontinuation on cognitive function in NH residents with dementia [11]. Discontinuation may be less efficacious on a fluctuating and multicausal outcome like NPS, a container of many different behaviours (e.g. agitation, apathy, hallucinations, shouting). The association of neuropsychiatric functioning with blood pressure, AHT or any other single component intervention is inherently meagre. The same can be said for QoL. And therefore the number needed to harm of AHT on neuropsychiatric functioning or QoL is probably too high to expect clinical significant improvements of AHT discontinuation. Finding a positive effect on neuropsychiatric functioning may be further complicated by the relatively low baseline NPI-NH scores (around 12) in the DANTON study.

But if the term refers to the setting of the nursing home, the conclusion can be challenged. Other relevant outcomes such as cognitive function or risk of falls or death may be positively influenced by AHT deprescribing but evidence is conflicting [12, 13].

But even in patients in who no direct benefit can be expected, deprescribing may be indicated. The most important reason for deprescribing being that prevention of major adverse cardiovascular events (MACE) is considered no longer relevant due to changed treatment goals and the patient or caregiver does not (wish to) continue AHT, accepting potential risks. This means that an earlier diagnosis ‘hypertension’ is disregarded leading not only to discontinuation of medication but also of diagnosis-related assessments and non-pharmacological treatments (‘undiagnosing’) [14].

Deprescribing in cases where only a hypothetical future risk–benefit imbalance exists, a more cautious approach is required. In these situations, potential benefits of therapy will end, whilst potential risks are introduced. In the short term, there is a potential for rebound effects (e.g. tachycardia with beta-blockers) or the re-emergence of previously well-managed symptoms. In the long term, deprescribing preventive medication may increase the risk of MACE.

In the DANTON study, although more SAEs were reported in the discontinuation group, this difference was not statistically significant, and cardiovascular events were not predominantly responsible for these outcomes. Given the study’s early termination, these findings do not conclusively demonstrate that AHT deprescribing in nursing home residents with dementia (and limited life expectancy) is unsafe.

Deprescribing AHT in residents with dementia may still be indicated. However, in managing polypharmacy in frail older adults, this deprescribing must always be part of total optimization of pharmacotherapy at should not be executed as an isolated goal [15]. In frail older persons, this requires a process of advance care planning and shared decision-making with the patient or their caregiver, in which future treatment goals, potential reasons for deprescribing, the uncertainties surrounding potential benefits and risks of deprescribing and strategies for monitoring of effects are discussed. This may lead to acceptance of an increased risk of MACE or death.

Frail older adults are a heterogeneous population and should not be treated as homogeneous or as sharing the same risk–benefit profile. RCTs provide group-level evidence but cannot determine whether deprescribing is beneficial or safe for an individual frail older person. Evidence-based decision-making requires consideration of the individual’s context alongside clinical experience. The DANTON study does not show that deprescribing AHT in nursing home residents is unsafe, but underscores the need for a balanced perspective on the uncertainties and complexities inherent in deprescribing, particularly when discontinuing medications that were initially indicated.

Declaration of Conflicts of Interest:

None declared.

Declaration of Sources of Funding:

None declared.

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