Potentially Inappropriate Prescribing in a Falls Clinic Using the STOPP & START Criteria

Background Potentially inappropriate prescribing which may lead to adverse drug events and linked to polypharmacy is becoming increasingly common in older patients. Objective This study applied the STOPP/START criteria to a clinical registry to determine the burden and prole of potentially inappropriate prescribing among patients attending a falls clinic. Data of individuals aged ≥ 65 years referred to the falls and syncope clinic were extracted from the falls registry. Potentially inappropriate prescribing was determined with the STOPP/START version 2 criteria. The relationship between potentially inappropriate prescribing with polypharmacy ( ≥ 5 medications), comorbidities and clinical variables were determined using Pearson’s chi-square and potential confounders adjusted for with multivariate regression.


Introduction
Global population ageing is associated with increased comorbidities, with increased deaths from ischaemic heart disease, stroke and chronic pulmonary disease. This leads to the use of multiple medications with the proportion of people aged ≥ 65 years consuming ve or more medications in UK increasing from 12 to 49% over the past two decades [1] [2]. Older age is also associated with increased adverse events with a systematic review reporting odds ratio (OR) for adverse drug events of 1.02 to 4.03 for individuals aged ≥75 years [3]. With increased use of prescribed medications, the risk of inappropriate prescribing also increases. Inappropriate prescribing may imply the prescription of medications with no clinical indication or when the risk of medication related harm outweighs the bene t of treatment, particularly when safer alternatives exist. The risk of adverse drug events is, therefore, further exacerbated with inappropriate prescribing [4].
Falls occur in one in four individuals aged ≥65 years [5]. With rapid population ageing, falls represent increasingly important public health concern. Falls are more likely to occur as a result of age-related muscle weakness which affects the balance, gait, and mobility; and/or modi able risk factors such as medication use, poor lighting, and unsafe environment [6]. In many instances, it is the synergistic effect of polypharmacy and use of falls-risks-increasing drugs (FRIDs) that contributes to increased falls risk [7] [8]. The relationship between inappropriate medication prescribing and falls in older adults has not been well studied [9].

AIM OF STUDY
The STOPP/START represents a set of criteria intended for clinical use to identify potentially inappropriate prescribing (PIP). Since its rst iteration in 2008, it has been evaluated in hospital and community settings in general population [10], [11]. Its use in falls assessment remains relatively unestablished. This cross-sectional study seeks to evaluate the utilization of the STOPP/START criteria in determining the burden of potential inappropriate prescribing (PIP) in older patients attending a falls and syncope clinic and to determine factors associated with potentially inappropriate medications (PIMs). If found suitable, the STOPP/START criteria could be used clinically to help identify PIP in the falls clinic settings.

Sample Characteristics
Of the 531 patients' data extracted, 110 (20.7%) patients were younger than 65 years and excluded from the study. Data from 421 patients' ages ranged from 65 to 95 years, with a mean age of 77.8 ± 6.7 years were analysed. 207 (49.2%) were aged 75 to 84 years old and 53.4% were women. Injuries from falls were reported by 15.7%; 9.5% experienced fractures, 5.9% required hospitalization and an additional 5.2% visited the doctor or Emergency department for treatment of injuries. The three most prevalent co-existing diseases observed were hypertension (57.2%), diabetes (34.0%), and dyslipidaemia (23.0%) ( Table 1). Of the sample population, 311 (73.9%) had either PIMs, or POMs or both PIMs and POMs. PIMs and POMs are reported separately below.

Polypharmacy
Polypharmacy was observed in 177 (42.1%) of the sample population. 169 (95.5%) were exposed to at least one PIM (OR = 27.3; 95% CI = 12.9 to 58.0) ( Table 2). The presence of polypharmacy detected the presence of PIM with a sensitivity of 62% and speci city of 94%. The presence of polypharmacy was independently associated with the presence of any PIM following adjustment for age, sex, dizziness, falls indoors, falls outdoors, hospital admission, diabetes, heart disease, stroke, depression and visual problems (odds ratio = 18.64; 95% con dence interval = 8.46 to 41.08) (Model 2). Comorbidities Eighty-two patients (20.0%) did not have any record of past medical history whilst 262 (62.1%) had two or more co-existing diseases of whom 214 (81.7%) were exposed to one or more PIM (OR = 7. 36.6% of those with comorbidities experienced potential prescribing omissions (OR = 6.45; 95% CI = 3.47 to 11.99). POMs within the cardiovascular system accounted for 41.0% of the total POMs with omissions of antiplatelet therapy (30 instances); statin therapy (3 instances); omission of beta-blocker with ischaemic heart disease (17 instances); and omission of anticoagulants in patients with atrial brillation (7 instances). Omission of Vitamin D and calcium supplement in patients with known osteoporosis and/or previous fragility fracture was observed in 26 instances (Fig. 3).

Discussion
Application of the STOPP/START checklist to the falls and syncope data registry found that PIP was present in 74% individuals aged 65 years and over attending the falls and syncope service at a teaching hospital in Malaysia, compared to 42.1% with polypharmacy. PIMs were present in 65.5% of the overall study population accounting for 84.5% of all patient prescriptions, while POMs were observed in 26% of all older individuals attending the clinic. Both polypharmacy and multiple comorbidities were independently associated with PIMs, and the presence of polypharmacy was 94% speci c for presence of PIMs.
The STOPP/START checklist was found unwieldy with the presence of 114 criteria [15]. However, once the researcher is familiarised with the criteria, it was possible to evaluate each patient's medication list within four to eight minutes. The use of the STOPP/START adds to rigor and provides standardization to the assessment of medication lists. However, ve out of six of all prescriptions were then agged as PIM in our clinic setting and three out of four of all patients had PIP from either PIM or POM or both PIM and POM. This was actually comparatively lower than the 98% reported by a recent study conducted in a falls and syncope clinic in the Netherlands [16]. While this could imply that the pattern of use of medications in our setting is far from desirable, the STOPP/START tool may conversely be interpreted as overly sensitive in identifying PIP. However, the high number of falls-risk increasing drugs detected and the case that these individuals are being seen for falls or symptoms that may predispose to falls, suggests that inappropriate prescribing is a common issue in the falls and syncope clinic setting.
A previous survey in a local hospital indicated that 60.0% of physicians and pharmacists have no knowledge of the availability of such medication review tools that could be used to improve prescribing to older patients [17]. Malaysia, like nearly all other South-East Asian nations, is experiencing population ageing. While the country is rapidly expanding its healthcare workforce and is now experiencing a glut in production of both doctors and pharmacists through the numerous private and public universities that have emerged in the last two decades, the curricula of these institutions have yet to respond to the urgent need of population ageing [18]. The lack of training of healthcare personnel in geriatric medicine may therefore explain the high level of PIP detected in this study. The use of PIP checklists such as the STOPP/START tool may therefore aid safe prescribing among doctors and also enhance the role of pharmacist in this context.
Inappropriate prescribing includes underuse or non-use of medications that are indicated and justi ed [19]. The phrase "potentially inappropriate" connotes that these medications or its omission has the possibility to result in more adverse risks than bene ts of achieving therapeutic goals for our patients. The prescriptions, may however, still be unavoidable due to other competing clinical priorities requiring careful weighing up potential harms and bene ts [20]. This issue was not explored in the current study. It also remains to be explored whether PIP could be reduced with inclusion of undergraduate geriatric curricula, upskilling of existing healthcare work force, or application of prescribing checklists for older persons.
The presence of comorbidity in 62% and polypharmacy in 42% of our study population is comparable to two other studies conducted on older patients in nursing homes in Malaysia which identi ed the presence of polypharmacy in 44-48% [21] [22]. The increase in the number of PIMs associated with the number of prescribed medications had been reported previously in many other studies [23]- [25]. Notably, a recent study concluded that it is the combination of PIMs and polypharmacy that increases the risk of falls in the older patients [7]. In resource limited setting, the STOPP/START may be applied selectively to those with polypharmacy with 94% speci city for detection of PIM, though sensitivity was limited at only 62%.
However, with the potential harm that may emerge from PIP, resource allocation towards better detection of PIP should be considered. Emphasis towards further research on the measuring of adverse events as a result of PIP may subsequently enable effective strategies to reduce PIP among older persons.
Fall-risk-increasing drugs accounted for 53% of all PIMs in previous study [26] which was consistent with our study (54.8%), and further established that 49% of all PIM in our fall clinic setting were vasodilators. The high usage of vasodilators and cardiovascular drugs would be attributable to cardiovascular morbidity within this population. The rising burden on non-communicable disorders within developing nations, suggests that potentially inappropriate use of such drugs is likely to increase unless action is taken to both reduce non-communicable disease burden as well as to improve the quality of prescriptions. A previous study has, however, challenged assumptions that antihypertensives was associated with increased risk of falls. While use of two or more antihypertensives was associated with increased falls risk, this was then attenuated by age and comorbidities [27]. The relatively fewer patients on psychotropic or neuroleptic drugs could be attributed to tight control of such drugs by regulatory agencies as well as possible dire shortage of psychiatry services. The extent by which deprescribing should occur or blood pressure lowering and secondary preventive treatment be withheld remains unclear and has been a hotbed for debate since conclusive evidence remains elusive [28].
Potentially omitted medications were identi ed in one in four individuals, though we had discounted the omission of vaccinations, which was not recorded in 100% of our sample. A national adult vaccination programme does not currently exist, and few healthcare professional and adult patients recognise the needs or bene ts of immunization in older adults. Our ndings were consistent with a previous prescribing omission study that demonstrated 22.7% prescribing omissions in the primary care setting [29]. Omissions of secondary prevention medications featured prominently. Under-treatment of cardiovascular diseases may result in cardiac rhythm disorders and increased risks of orthostatic hypotension, leading to gait and balance impairment and falls [16]. Omission of necessary medicines and under-treatment in older adults to reduce long term morbidity and disease progression can be just as detrimental as over-prescribing [30]. However, within the STOPP/START criteria, medications may be highlighted as PIM such as vasodilators in individuals with falls; but the omission of the same drug will then be considered a POM as in the case of omitting beta-blockers in ischemic heart disease. It was not possible to detect whether the POMs identi ed in this study were omitted because of other competing risks, further highlighted the issue that PIP were not always avoidable. The identi cation of PIP using checklists therefore still requires clinical judgement as to whether deprescribing or prescribing should occur. Clear documentation and communication should be advocated as multiple clinical teams often provide care for the same patient with multiple comorbidities. Lack of adequate communication often lead to inconsistencies in management of older patients resulting in polypharmacy and potential harm. [31].
This study is limited by the retrospective analysis of a patient registry. The lack of accompanying clinical assessments precluded the inclusion of ve STOPP/START criteria. The medication list was consolidated by the electronic prescribing which ensured that all prescribed medications arising from the study institution were recorded, although some prescriptions obtained from outside the hospital setting, such as private general practitioners' clinics may be missed out. The hospital, however, had its own primary care centre with integrated medical records, where many of the patients also attended. While application of the STOPP/START checklist among older adults attending falls and syncope clinic no doubt highlighted PIP as almost ubiquitous, the underlying structural issues as well as potential solutions have yet to be established. Future research studies should include implementation research as well as randomised controlled studies on establishing the use of STOPP/START to identify PIP as well as to identify effective strategies to reduce PIP and changes in clinical outcomes associated with reduction in PIP.
Using the STOPP/START criteria, PIP was present in three out of four individuals aged ≥ 65 years attending a falls and syncope service at a tertiary hospital in Malaysia. PIP increases with polypharmacy and co-morbidities. Further evaluation is needed to identify structural issues leading to the high level of PIP as well as to guide implementation of PIP checklists and strategies to effectively and safely reduce PIP.

Declarations
Funding This work was supported by an Impactful Interdisciplinary Research Grant (lIRG024A-2019) awarded by the Health and Wellbeing Research Cluster, University of Malaya.

Con ict/Competing Interests
None declared

Availability of Data and Material
The data that support the ndings of this study are available from the corresponding author upon reasonable request

Code Availability
Available upon reasonable request, if applicable