Yu Ming, PhD1, Aleksandra A. Zecevic, PhD1, Richard G. Booth, RN, PhD2, Susan W. Hunter, PhD3, Rommel G. Tirona, PhD4, Andrew M. Johnson, PhD1
1School of Health Studies, Western University, London, ON
2Arthur Labatt Family School of Nursing, Western University, London, ON
3School of Physical Therapy, Western University, London, ON
4School of Physiology and Pharmacology, Western University, London, ONDOI: https://doi.org/10.5770/cgj.25.569
ABSTRACT
Background
Serious injuries secondary to falls are becoming more prevalent due to the worldwide ageing of societies. Several medication classes have been associated with falls and fall-related injuries. The purpose of this study was to describe medication classes and the number of medication classes prescribed to older adults prior to the fall-related injury.
Methods
This population-based descriptive study used secondary administrative health-care data in Ontario, Canada for 2010–2014. Descriptive statistics were reported for Anatomic Therapeutic Chemical 4th level medication classes. Frequency of medications prescribed to older adults was calculated on different sex, age groups, types of medications, and injures.
Results
Over five years (2010–2014), 288,251 older adults (63.2% females) were admitted to an emergency department for a fall-related injury (40.0% fractures, 12.1% brain injury). In the year before the injury, 48.5% were prescribed statins, 27.2% antidepressants, 25.0% opioids, and 16.6% anxiolytics. Females were prescribed more diuretics, antidepressants, and anxiolytics than males; and people aged 85 years and older had a higher percentage of diuretics, antidepressants, and antipsychotics. There were 36.4% of older adults prescribed 5–9 different medication classes and 41.2% were prescribed 10 or more medication classes.
Discussion
Older adults experiencing fall-related injuries were prescribed more opioids, benzodiazepines, and antidepressants than previously reported for the general population of older adults in Ontario. Higher percentage of females and more 85+ older adults were prescribed with psychotropic drugs, and they were also found to be at higher risk of fall-related injuries. Further associations between medications and fall-related injuries need to be explored in well-defined cohort studies.
Key words: medication prescription, fall-related injuries, fall-related fractures, older adults
Falls are the leading cause of both fatal and non-fatal injury in older adults.(1) Nearly one-third of older adults fall every year.(2–3) Minor injuries, such as bruises or lacerations, occur in 30–50% of falls, while 5–10% of falls lead to serious injuries such as hip fractures or traumatic brain injury.(4–9) Fall-related injuries can also result in adverse consequences such as reduced quality of life,(10) higher possibility of admission to long-term care facilities,(10) and increased risk of death.(11)
Numerous fall-related risk factors in older adults have been identified through past research. Specific use of certain medications and concurrent use of more than four medications have consistently been reported to be associated with both increased risk of falls and fall-related injury in this population.(12–17) Widely acknowledged fall risk-increasing drugs (FRIDs) include antihypertensive agents, diuretics, antidepressants, analgesics, anti-epileptics, and sedative/hypnotics.(18–22)
While previous research has commonly investigated the association between specific and known FRIDs and fall-related injuries (e.g., benzodiazepines,(23–24) anti-hypertensive medications,(25–26) and antidepressants(27–28)), limited evidence currently exists regarding medication classes of other than FRIDs that were prescribed to older adults prior to a fall-related injury. Providing a more comprehensive picture of medication classes prescribed to older adults before the occurrence of a fall-related injury is necessary to expand our knowledge on medications that may induce any fall-related injury. Therefore, the purpose of this study was: 1) to describe medication classes and numbers of medication classes prescribed to older adults within one year prior to the fall-related injury; and 2) to describe medication classes prescribed to older adults within one year prior to fall-related fractures and fall-related brain injury, as these two types of injury are of high prevalence and can cause serious consequences.(29–31)
We conducted a population-based, descriptive study of medication classes prescribed to older adults who experienced at least one fall-related injury from 1 January 2010 to 31 December 2014, using Ontario health-care administrative data held by the provincial data steward ICES. Ontario is the largest province in Canada, with a population of over 13 million and 2.2 million older adults over the age of 65,(32) all of whom have access to universal health-care services. ICES is an independent, non-profit research institute whose legal status under Ontario’s health information privacy law allows it to collect and analyze health-care and demographic data, without consent, for health system evaluation and improvement. ICES is a prescribed entity under section 45 of Ontario’s Personal Health Information Protection Act. Section 45 authorizes ICES to collect personal health information, without consent, for the purpose of analysis or compiling statistical information with respect to the management of, evaluation or monitoring of, the allocation of resources to or planning for all or part of the health system. Projects conducted under section 45, by definition, do not require review by a Research Ethics Board. This project was conducted under section 45, and was approved by ICES’ Privacy and Legal Office.
Older adults aged 66 years and older who experienced a fall-related injury over the study period and resided in Ontario were included in this study. We chose the study period to be between 2010 and 2014 because it aligns well with the first of ‘baby boomers’ reaching the age of 65. The result of this study can serve as a baseline characteristics description for comparison with our future fall-related injuries research results. A fall-related injury was defined by combining at least one ICD-10 code for falls (W00-W19) with at least one code for injury (S00-S99, T00-T14) (Appendix A). The Emergency Department visit date for a fall-related injury was defined as the index date. Fall-related injuries of interest in this study were: 1) any fall-related injury; 2) fall-related fracture; and 3) fall-related traumatic brain injury (TBI). Fall-related fracture was identified through presence of at least one specific fracture S code (S02, S12, S22, S32, S42, S52, S62, S72, S82, S92, T02, T08, T10, T12, T142) and one W code (W00-W19). Fall-related traumatic brain injury was identified by presence of at least one specific concussion and brain injury code (S06, S099) and one W code (W00-W19). If a patient had multiple falls during the time period, only the first fall was included.
We used records arising from several databases held by ICES, including: 1) the Ontario Drug Benefit (ODB) database, which provides prescription drug coverage data for residents over the age of 65, including individuals in long-term care homes;(33) 2) the Discharge Abstract Database (DAD), which records information on all hospital admissions and discharge diagnosis; 3) the National Ambulatory Care Reporting System (NACRS), which captures information on visits to emergency departments and community-based ambulatory care facilities; and 4) the Ontario Registered Persons Database (RPDB), which contains demographic information for Ontario residents. ICES also applied validated case definition, including diabetes, chronic obstructive pulmonary diseases (COPD), asthma, hypertension, and dementia to each older adult and produced flags for these comorbidities. These datasets were linked using a unique encoded identifier, which ensured the confidentiality of personal and health information. In this study, socio-demographic data were extracted from the RPDB, primary diagnosis data arose from both NACRS and DAD, and medication prescriptions were drawn from ODB.
Medication information extracted from the ODB database used the Drug Identification Number (DIN) assigned by Health Canada.(34) Each DIN uniquely identifies the manufacturer, trade name, active ingredients, strength of active ingredients, pharmaceutical form, and route of administration.(34) For better understanding and comparability with the results of other studies, DIN codes were converted into Anatomical Therapeutic Chemical (ATC) level 5 codes, which represent the chemical substance.(35) Medication prescription information was reported on the 4th level of ATC codes in this study. ATC 4th level is the level used to count number of different medications as it is the level which aggregates medications just above their descriptive chemical substance.(36,37)
The primary outcome of this study was medication classes prescribed to older adults within one year prior to any fall-related injury, fall-related fractures, and fall-related traumatic brain injuries. Canadian Institute of Health Information reported medication use in general older adult population during the whole year of 2016.(37) To allow contextualization and comparison of our results with their findings,(37) we chose one year look-back window for medication use in older adults who have experienced fall-related injuries. We also explored medication prescription patterns in both fall-related fractures and fall-related brain injuries and medications taken in the year prior to these specific injuries. Finally, the number of ATC 4th level medication classes prescribed to each older adult within a year was calculated and summarized into four categories: 0–4 medication classes, 5–9 medication classes, 10–14 medication classes, and 15 or more medication classes.(37)
Descriptive analysis summarized the cohort baseline characteristics such as age, sex, age group, and income quintile. Income quintile is a measure of socioeconomic status that divides the population living in the same dissemination area into five income groups (1 represents the lowest income) with approximately 20% of the population in each group.(38) The dissemination area was determined from the older adults’ residential postal code and statistics Canada Census data.(39) Prevalence of diabetes, COPD, asthma, hypertension, and dementia was also calculated using descriptive statistics. The fall-related injury (any injury type) was reported for each year and as a five-year total (2010–2014).
The percentage of people prescribed each ATC 4th level medication class was calculated by dividing the number of people who were prescribed a certain class within a year prior to a fall-related injury (numerator) by the total number of people who experienced a fall-related injury (denominator). The top 20 medication classes with the highest number of users were summarized as the percentage of female and male users, and percentage of different age-group users (i.e., 66–74, 75–84, 85+). The same analysis was repeated for subgroups of older adults who experienced fall-related fractures and fall-related TBIs. The difference between percentages of female and male older adults prescribed certain medication classes was determined by Wilcoxon rank-sum test and the comparison among different age groups was determined by Kruskal-Wallis test. All analyses were conducted with SAS 9.4 (SAS Institute Inc., Cary, NC).
A total of 288,251 older adults experienced any fall-related injury during the time frame of interest. Fall-related fractures made up 40.0% of all fall-related injuries, superficial injuries were 23.2%, open wound were 16.3%, traumatic brain injury were 12.1%, sprains and strains were 5.0%, and other injuries were 3.5%. The mean age was 78.3 ± 7.8 years old and 63.2% of the older adults were female. Over three quarters (76.9%) were diagnosed with hypertension, 30.5% with diabetes, 26.9% with COPD, 15.8% with dementia, and 15.0% with asthma (Table 1). Of the study population, 3.5% were not prescribed any medication classes within one year before the injury, while 18.9% were prescribed 1–4 different medication classes, 36.4% were prescribed 5–9 different medication classes, 26.0% were prescribed 10–14 different medication classes, and 15.2% were prescribed more than 15 different medication classes. Complete medication classes prescribed are provided in Appendix B, Table B1.
TABLE 1 Characteristics of older adults who experienced fall-related injuries in 2010–2014.
HMG-CoA reductase inhibitors (C10AA), commonly known as statins and used to treat high cholesterol, were the most commonly prescribed medication class, used by nearly half (48.5%) of the study population (Table 2). They were also the most frequently prescribed medication class in analyses stratified by sex and age subgroups (Figure 1). More than half (54.8%) of males were using statins before they experienced any fall-related injury. In the 75–84 age group, 53.4% used statins and the percentage dropped to 42.8% in the group of 85 years and older adults. The most prescribed statin (Appendix B, Table B2) was atorvastatin (24.3% in all older adults who experienced fall-related injuries), followed by rosuvastatin (17.2%) and pravastatin (1.9%).
TABLE 2 Top 20 medication classes prescribed to older adults prior to a fall-related injury, percentage of users, 2010–2014
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FIGURE 1 Top 10 medicationsa prescribed to older adults of different age group before they experienced a fall-related injury
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Proton pump inhibitors (PPIs, A02BC) were the second most prescribed drug class, with 34.3% of all older adults. For age groups 75–84 and 85 years and older, a slightly greater percentage of PPI use was found (36.2% and 36.5%, respectively), while the age group 66–74 years old had somewhat lower prevalence (30.6%, Figure 1). Commonly prescribed medications included pantoprazole (14.2%), rabeprazole (13.2%), lansoprazole (5.1%), and omeprazole (4.7%).
Four drug classes for the management of hypertension were noted among the top 10 drug classes. Angiotensin-converting enzyme inhibitors (ACEIs, C09AA) were prescribed to 33.9% of male and 26.1% females. Most common ACEIs were ramipril (14.8%), perindopril (7.0%), enalapril (2.4%), and lisinopril (2.0%). A higher percentage of males (27.8%) were prescribed beta-blocking agents (BBs) than females (24.8%). BBs included metoprolol (11.5%), bisoprolol (7.6%), and atenolol (6.7%). Agents acting on the renin-angiotensin system (ARBs, C09CA) included candesartan, valsartan, irbesartan, losartan, and telmisartan. Thiazides (C03AA) included hydrochlorothiazide (15.2%) and indapamide (2.2%). ARBs and thiazides were prescribed in higher percentage to females than males. The prescription of agents for treatment of high blood pressure increased with age (Figure 1). The percentage of the 85 years and older age group prescribed ACEIs, beta-blocking agents and dihydropyridine derivatives were the highest among the three age groups.
Biphosphates (M05BA) and thyroid hormones (H03AA) were prescribed to 28.3% and 23.1% of females, but only to 7.1% and 10.0% males, respectively. These two medication classes emerged as the most gender-specific among the older adults who experienced any fall-related injury. The percentage of older adults prescribed these two drug classes also increased with age (Figure 1), with the age group 85 years and older having the highest percentage.
Natural opium alkaloids (N02AA) were prescribed to a quarter of female and male older adults. For example, codeine and oxycodone were prescribed to 17.3% and 6.6%, respectively, of older adults who had fall-related injuries one year prior to the injury. The highest percentage of opioids prescription was noted for the age group 75–84 years. Older adults 85 years and older were prescribed fewer opioids than the other two age groups (Figure 1). Benzodiazepine derivatives were prescribed to 19.0% females and 12.4% males, with an increase with age to 18.5% in 85 years and older people. Lorazepam was prescribed to 12.2%, oxazepam to 2.7%, and clonazepam to 2.7% of older adults. For antidepressants, such as selective serotonin reuptake inhibitors (SSRIs, including citalopram, escitalopram, fluoxetine, etc.) and tricyclic antidepressants (TCAs, including amitriptyline, clomipramine, and doxepin), there was a higher percentage of female users than male users, namely 16.4% female, 11.9% male for SSRIs and 13.5% female, 10.7% male for TCAs.
Fall-related fractures were diagnosed in 115,230 older adults (40.0% of all older adults with any fall-related injury). More women (70.7%) than men (29.3%) experienced fall-related factures. For 85 years and older age group, the number of females (22,231) was almost three times as many as males (7,742). Statins and PPIs were still the top two most commonly prescribed medication classes. A higher percentage of males were prescribed statins, ACEIs, and BBs than females, while a higher percentage of females were prescribed bisphosphonates, dihydropyridine derivatives, and thyroid hormones. As for age differences, adults 85 years and older had the highest percentage of prescribed ACEIs, BBs, bisphosphonates, dihydropyridine derivatives, thyroid hormones, benzodiazepine derivatives, agents acting on the renin-angiotensin system, SSRIs, fluoroquinolones, and emollients (Table 3).
TABLE 3 Top 20 medication classes prescribed to older adults with fall-related fracture, usage rate by sex and age group, 2010–2014
Fall-related TBIs was observed in 34,810 older adults (12.1% of all older adults with any fall-related injury), 20,246 occurred in females (58.7%) and 14,364 in males (41.3%). Nearly a third (31.7%) of older adults who experienced fall-related TBIs were in the 66–74 age group, with 39.9% in the 75–84 and 28.4% in the 85+ age groups, respectively. A higher percentage of males diagnosed with fall-related traumatic brain injury were prescribed statins, ACEIs, and BBs than females, while higher percentage of females were prescribed opioids, benzodiazepine derivatives, bisphosphonates, and thyroid hormones. As for age groups, adults 85 years and older had the highest prescriptions of ACEIs, BBs, dihydropyridine derivatives, bisphosphonates, thyroid hormones, sulfonamides, benzodiazepine derivatives, SSRIs, fluoroquinolones, emollients, TCAs, and contact laxatives (Table 4).
TABLE 4 Top 20 medication classes prescribed to older adults with fall-related traumatic brain injury, by sex and age group
Using health-care administrative data, this study has described the medication classes prescribed to older adults in one year prior to a fall-related injury and two specific fall-injury types (i.e., fracture and traumatic brain injury). The results showed that among older adults sustaining any fall-related injury, 48.5% were prescribed statins, 34.3% PPIs, 25.0% opioids, and 16.6% anxiolytics. Similar patterns of medication prescription were also found for fall-related fractures and traumatic brain injury. Notably, 36.4% of older adults were prescribed 5–9 different medication classes and 41.2% were prescribed 10 or more medication classes within one year prior to fall-related injuries.
The findings of this study also indicate that medications prescribed to older adults who had any fall-related injury were similar—but not the same—to medications prescribed to the general population of older adults in Ontario.(37) CIHI reported that, in the whole year of 2016, there were 51.7% and 17.3% of Ontario general population of older adults (OGP-OAs) who were prescribed statins and agents acting on RAS,(37) while in our study, 48.5% and 16.3% of older adults who had fall related injury (FRI-OAs) were prescribed statins and ARBs within the year before the injury. However, compared to prescription in OGP-OAs, higher percentage of FRI-OAs were prescribed with ACEIs, BBs, opioids, bisphosphonates, benzodiazepine derivatives, thiazides, and SSRI. For example, CIHI reported there were 15.4% of OGP-OAs prescribed opioids, while in our study, 25.0% of FRI-OAs were prescribed opioids the year before their fall-related injury. The percentage of being prescribed SSRI in FRI-OAs and OGP-OAs were 14.6% and 10.5% respectively, bisphosphonates were 20.4% and 9.4% respectively, and benzodiazepine derivatives were 15.2% and 10.8% respectively.
From the above comparison, a finding is that all medication classes (except for bisphosphonates) with a higher percentage of prescription in older adults who had any fall-related injury were recognized as FRIDs. These classes of medications have been repeatedly identified to be related to falls and fall-related injury.(40–43) In this aspect, findings from our studies were supportive to previous studies on FRIDs and their association with falls and fall-related injury.
In this study, a number of medication classes were prescribed to a high percentage of older adults the year before they had fall-related injury, such as statins (48.5%), PPIs (34.3%), bisphosphonates (20.4%), thyroid hormones (18.3%), glucocorticoids (17.0%), and fluoroquinolones (15.2%). Unfortunately, research regarding the association between these medication classes and fall-related injuries has not been well-established.(26,44) The role of these commonly prescribed medication classes on fall-related injury in older adults needs to be disclosed as well.
Medications can be seen as a surrogate for a person’s health status and the number of medications was a valid proxy for multi-comorbidities.(45) Using multiple medications concurrently is common in older adults with multi-comorbidities and is associated with adverse outcomes such as mortality, falls, injuries, adverse drug reactions, and prolonged length of stay in hospital.(46–48) The risk of having adverse consequences and experiencing harm increased with each additional medication because of complicated drug-drug and drug-disease interactions.(49) Our study showed that 77.9% of older adults who had any fall-related injury were prescribed five or more different classes of medication within one year before the injury and 41.2% were prescribed 10 or more different classes of medication. CIHI reported that 65.7% general population of older adults in Canada were prescribed five or more medication classes and 26.5% were prescribed 10 or more medication classes in the year of 2016.(37) Compared with the general population of older adults, a higher percentage of older adults who experienced fall-related injuries were prescribed multiple medication classes before the injury. Untangling multiple medications prescribed to older adults by enhancing communication between patients and health-care providers, and improving cooperation of pharmacists, family doctors, and specialists in prescribing practices will be important in future research.
The strengths of this study are the large number of observations and provincial representativeness. This study included data for over a quarter million older adults and provided detailed information on demographics, comorbidities, and strictly defined fall-related injury using ICD-10-CA codes. All the data were obtained from ICES databases which were reported to have excellent data completeness(50) and high quality as per previous studies.(51–53)
Several limitations are associated with this study. First is the inherent limitation of administrative data that may lead to underreporting of some diagnoses,(54) which might have been omitted during the coding process. Second, only dispensed drugs were recorded in the ODB database, and the information collected through the ODB database could be an underestimation of prescriptions. Additionally, prescription (and even dispensing) cannot be equated with actual use. If older adults forgot to take medications as they were instructed, the registry data could be an overestimation of drug use; while on the other hand, if older adults get medications with multiple pharmacies, the registry data could underestimate the actual medication use.
This study described the medications classes and numbers of medication classes prescribed to older adults prior to a fall-related injury. Gender difference in medication prescribed was noted, specifically more females were prescribed antidepressants (SSRIs and TCAs) and anxiolytics (short-acting benzodiazepines such as lorazepam and long-acting such as clonazepam). A higher percentage of people 85 years and older were prescribed antihypertensive agents (ACEIs, BBs and dihydropyridine derivatives) and anxiolytics (benzodiazepines). There were 77.6% older adults were prescribed five or more different medication classes prior to any fall-related injury. Well-designed cohort studies are needed to determine the association between medication classes and different types of fall-related injuries.
This study was supported by ICES, which is funded by an annual grant from the Ontario Ministry of Health and Long-Term Care (MOHLTC). The opinions, results, and conclusions reported in this paper are those of the authors and are independent from the funding sources. No endorsement by ICES or the Ontario MOHLTC is intended or should be inferred.
We have read and understood the Canadian Geriatrics Journal’s policy on conflicts of interest disclosure and declare there are not conflicts of interest.
This research did not receive external funding.
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TABLE B1. Numbers of older adults being prescribed with different medication classes within one year prior to fall-related injurya
TABLE B2. Numbers of older adults being prescribed with different generic names within one year prior to fall-related injury
Canadian Geriatrics Journal, Vol. 25, No. 4, December 2022