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.