Discussion
Polypharmacotherapy is a common phenomenon in older adults and is
associated with worse physical and cognitive outcomes which may be
aggravated by the summative effect of drugs carrying ACB. Our study, the
first we are aware of, clearly demonstrates that age, ACB,
polypharmacotherapy, but not comorbidity, are associated with
significantly higher falls risk in older patients.
Our results demonstrate a high incidence of polypharmacotherapy in older
hospitalised patients (78.3%) consistent with previous epidemiology
studies (74%).13 88% of patients admitted with a
fall were exposed to polypharmacotherapy. Our data also highlight a
statistically significant positive association between
polypharmacotherapy and cumulative ACB and the incidence of falls. Our
data also show a higher odds ratio between polypharmacotherapy and falls
compared to comorbidity. This implies that the presence of
polypharmacotherapy or the increase in ACB score represents a more
significant increase of falls and harm. In addition, of patients
admitted with fall, 29·8% was found to have drug-related orthostatic
hypotension, 24·7% had drug-related bradycardia, 37·3% were
taking regular centrally acting agents and 12·0% were taking
inappropriate hypoglycaemic agents. All these interconnected factors
contribute to falls risk and play a crucial role in the progression of
the cycle of frailty and has been linked to poorer outcomes for older
patients in terms of maintaining independence and
mortality.14,15
Undesirable effects of anticholinergic medications arise from their
effect on G-protein coupled muscarinic receptors present in both
peripheral and central nervous systems. Peripheral anti-muscarinic
effects are usually associated with short term use of anticholinergics.
However, many of these medications cross the blood brain barrier and
affect the central nervous system directly, and this is more pronounced
in older adults where age-related changes in the blood brain barrier
disrupt its function.16 By demonstrating the impact of
polypharmacotherapy and cumulative ACB in older adults, particularly
with respect to falls in this study, we highlight the importance of
pharmacological rationalisation and deprescribing.
We found a progressive numerical decline in polypharmacotherapy and ACB
without statistical significance due to numbers (Figure 2). This might
be attributed to changes in physiology and drug metabolism with age such
that some drugs become obsolete and/or because this population may have
greater contact with healthcare professionals, either in primary or
secondary care, who adjust pharmacotherapy.
Falls are often multifactorial and are both an association and cause of
increased frailty. Research into interventions to reduce the risk of
falls is ongoing, but even multifaceted interventions have only shown
modest benefits.17 Identifying culprit medications and
drug classes with a view to develop a structured medication review for
those at risk of falling could therefore improve outcomes and relieve
pressure on the healthcare system.
NICE guidance on falls in older people recommends that people who have
had a fall or are at increased risk of falling should have a medication
review as part of a multifactorial risk assessment. It is recommended
that psychotropic medications which carry a high ACB should be
discontinued, if possible, to reduce their risk of falling. Despite it
being well proven and understood in the literature that ACB is linked to
poorer outcomes for older patients, awareness appears to remain low in
clinical environments. A study conducted in 2020 showed that there is a
limited understanding of the potential harms of starting regular
anticholinergic medications among clinical staff.18Therefore, the process of due pharmacovigilance remains to be embedded
into clinical practice amongst the wider medical team who care for
patients above the age of 65.
Our findings clearly validate the importance of rationalising and
balancing risks and benefits of starting medications with any ACB. There
are several validated tools that assess the burden of anticholinergic
drugs. Although there is heterogeneity in the clinical value of these
scales and an absence of an established gold standard, current evidence
suggests that the ACB score is of higher quality compared to other
tools.19 We therefore suggest the use of the online
based ACB calculator (accessible on http://www.acbcalc.com/) in
daily clinical activity to reduce potentially inappropriate medications
for older patients. An ACB score ≥3 confers a heightened risk of
cognitive and functional impairment, falls and mortality. As
demonstrated in our study, it is also important to consider lower
potential anticholinergic drugs as cumulative effects can lead to high
ACB.
Falls and their complications have significant clinical and financial
implications for secondary care, with an estimated cost the NHS of more
than £2.3 billion per year.20 Therefore, falls impact
quality of life, wellbeing, and healthcare resources. With appropriate
pharmacovigilance, medication rationalisation with regular review and
education towards reducing the need for initiating medications with ACB,
there are potentially enormous cost savings. This ranges from reduced
prescription costs, to preventing acute admissions related to falls and
their complications and costs associated with managing general frailty.
Further study and more thorough cost benefit analysis is awaited to
corroborate this.