Abstract
Background
Potentially inappropriate medications (PIMs) can lead to adverse outcomes. This study aimed to investigate the prevalence of PIMs in older Chinese outpatients with heart failure according to the 2019 Beers criteria and the factors associated with PIMs.
Methods
A cross-sectional retrospective study was conducted using electronic medical data during January 1, 2020 to December 31, 2020 from 9 tertiary medical institutions in Chengdu, China. Outpatients aged 65 and above who were diagnosed with heart failure were included. The 2019 Beers criteria were used to evaluate the PIM status of older outpatients, and binary logistic regression was used to identify potential risk factors for PIMs.
Results
There were 3626 prescriptions. The prevalence of PIMs among older outpatients with heart failure was 67.98% according to the 2019 Beers criteria. Diuretics, non-steroidal anti-inflammatory drugs (NSAIDs), benzodiazepine receptor agonist hypnotics, rivaroxaban, and dabigatran were the top five PIMs. The risks of PIMs were associated with the number of drugs prescribed and comorbidities. PIMs were shown to be more common in patients with polypharmacy (5–9 medications, OR: 10.403, 95% CI: 8.258–13.104, p < 0.001; ≥10 medications, OR: 35.018, 95% CI: 10.545-116.293, p < 0.001), valvular heart disease (OR: 1.537, 95% CI: 1.109–2.131, p = 0.010), and insomnia (OR: 2.655, 95% CI: 1.809–3.898, p < 0.001). While, medicare reimbursement (OR: 0.678, 95% CI: 0.570–0.808, p < 0.001) and visits to the geriatric departments (department of cardiology, OR: 1.687, 95% CI: 1.214–2.344, p = 0.002) were protective factors.
Conclusions
The prevalence of PIMs use was high among older Chinese outpatients with heart failure, according to this study. Multidisciplinary teams should cooperate to reduce PIMs in older adults.
Supplementary Information
The online version contains supplementary material available at 10.1186/s12877-024-05630-w.
Keywords: Potentially inappropriate medication, Older, Outpatient, Heart failure, Beers criteria
Background
Potentially inappropriate medications (PIMs) are defined as medications with potential harms that outweigh their possible benefits [1]. PIMs use is associated with adverse outcomes, such as adverse drug events and drug interactions, which can result in higher hospitalization, increased falls, hypofunction and mortality [2–4]. As a consequence, medical cost is increased and patient health is worsen. Schiavo et al. conducted a systematic review, which included 236,888,744 older adults, and they found that PIMs use was linked to higher costs of hospitalization, health care expenses and visits to emergency department [5]. PIMs use is common in older adults. Morin et al. found almost one half of older adults living in nursing homes were exposed to PIMs [6]. Praxedes et al. performed a systematic review to evaluate the prevalence of potentially inappropriate medicines according to Beers Criteria and the result showed that the mean prevalence was 65.0% [7]. Thus, PIM is a major health problem faced by the geriatric population.
There are many screening tools for PIMs, including implicit and explicit criteria. Implicit criteria to identify PIMs is based on the conditions of patients, and requires greater knowledge and practice of evaluators [8, 9]. Explicit criteria to identify PIMs is clear and easy to use, which is not affected by evaluators [8, 9]. Explicit criteria that have been published so far include Beers criteria, Canada National Consensus Panel, Australian List, NORGEP, French Consensus Panel, PRISCUS List, FORTA, STOPP/START, the EU(7)-PIM List, STOPPFrail, Lista IFAsPIAM, GheOP3S-Tool, et al. [9]. Among them, Beers criteria are the most commonly used. Beers criteria, now known as American Geriatrics Society Beers Criteria® for Potentially Inappropriate Medication Use in Older Adults, was initially published in 1991. Since 2011, the criteria has been stewarded by the American Geriatrics Society [10]. After several revisions, the latest version of Beers criteria was released in 2019 [10].
The incidence and prevalence of heart failure increase significantly with age due to age-related cardiovascular diseases and age-related changes in cardiovascular structure and function [11, 12]. Heart failure is the most common cause of hospitalization in older adults [11]. Patients with heart failure often suffer from multiple cardiovascular and non-cardiovascular diseases and might be prescribed multiple medications, which puts patients at high risk of PIMs [12, 13]. As pharmacotherapy of heart failure become more complex, polypharmacy and PIM has been a nonnegligible problem in older adults with heart failure [13]. Some studies investigated PIMs use in older patients with heart failure in other countries, and the prevalence was high [14, 15]. As far as we know, no study reported the prevalence and risk factors for PIMs use in Chinese older adults with heart failure. Therefore, we conducted a cross-sectional study in Chinese geriatric population. We extracted prescriptions of older outpatients attending tertiary medical institutions to screen PIMs by using the 2019 Beers criteria and analyze risk factors for PIMs. This study may provide epidemiological evidence for further research.
Methods
Setting and sample
The study was conducted in nine tertiary medical institutions located in Chengdu, a city situated in Sichuan province of China. Prescriptions of outpatients aged 65 and above, who suffered from heart failure or heart failure combined with other diseases were extracted during the period spanning from January 1, 2020 to December 31, 2020. If any information in the prescription was missing or incomplete, the prescription was excluded. The missing or incomplete items included gender, age, diagnosis, drug, dosage, administration route and dosing frequency.
Data collection
Data collection covered basic information and medication information of prescriptions. General information included prescription number, department name, patient gender, patient age, clinical diagnosis, medicare reimbursement, and prescription expenditure. Medication information included drug name, dosage form and strength, administration route, dosage, and administration frequency.
PIM evaluation
The 2019 Beers criteria were used for PIM evaluation. PIM evaluation was conducted independently by two researchers (Y Zhang and ZY Chen), and that with inconsistent results were referred to a third expert for arbitration. The 2019 Beers criteria cover five types of criteria including medications that are potentially inappropriate in older adults, medications that should typically be avoided in older adults with certain diseases or syndromes, drugs to be used with caution in older adults, drug-drug interactions that should be avoided in older adults, and medications that should be avoided or have their dosage reduced with varying levels of kidney function in older adults [10]. Kidney function of older outpatients were not available, thus the dosage adjustment based on kidney function were not evaluated, and we only use the other four criteria for PIM evaluation.
Statistical analysis
All statistical analyses were performed using SPSS version 26.0 software. Categorical variables were reported as absolute value and percentage value, while continuous variables were reported as average ± standard deviation (SD). Skewed distribution continuous variables were presented as median [interquartile range (IQR)]. Comparison between the frequencies of the categorical variables was assessed by a Pearson’s χ2 test. Variables (gender, age, number of diseases, number of medications, prescription expenditure, medicare reimbursement, departments, concomitant diseases) were included in multivariate logistic regression analysis to screen the risk factors affecting the occurrence of PIMs. A p value of less than 0.05 was considered to be statistically significant.
Ethics approval
This study protocol was approved by the Sichuan University West China Hospital Research Ethics Board (2020/651). All procedures performed in this study conformed to the standards of the 1964 Helsinki Declaration and subsequent relevant ethics.
Results
General characteristics
A total of 3,626 prescriptions were obtained, including 1,891 (52.15%) for females. The prescriptions in the three age groups (65–69, 70–79, ≥ 80) were 726 (20.02%), 1,740 (47.99), 1,160 (31.99%), respectively. The median age was 76 years old (IQR: 71, 81). The median number of diseases was 3 (IQR: 2, 4). 44.32% of the patients had 3 or 4 diseases, and 23.52% had 5 or more diseases. The median number of medications was 4 (IQR: 2, 5). 36.85% of the patients had polypharmacy (five or more medications). The median prescription expenditure was 154.45 Chinese Yuan (CNY) (IQR: 58.72, 421.22). Most of the patients (77.99%) spent less than 500 CNY on all the drugs of their prescriptions. 63.95% of the patients could be reimbursed for medication use. 69.55% of the patients visited to the department of cardiology and 7.12% to the department of geriatrics. Among the comorbidities, the top 10 were coronary heart disease, hypertension, atrial fibrillation and atrial flutter, diabetes mellitus, gastritis, myocardiopathy, renal dysfunction, valvular heart disease, chronic obstructive pulmonary disease, and insomnia. Among which coronary heart disease was the most common comorbidity, accounting for 44.76%. The basic characteristics of older outpatients with heart failure were shown in Table 1 (page 20–21, line 419–421).
Table 1.
Prescription characteristics between HF outpatient PIM prescription versus non-PIM prescription
| Characteristics | Total | PIM | Non-PIM | p value |
|---|---|---|---|---|
| N (%) | 3,626 | 2,465 (67.98) | 1,161 (32.02) | |
| Gender, n (%) | 0.059 | |||
| Male | 1,735 (47.85) | 1,153 (46.77) | 582 (50.13) | |
| Female | 1,891 (52.15) | 1,312 (53.23) | 579 (49.87) | |
| Age [IQR], n (%) | 76 [71, 81] | 0.274 | ||
| 65–69 | 726 (20.02) | 493 (20.00) | 233 (20.07) | |
| 70–79 | 1,740 (47.99) | 1,203 (48.80) | 537 (46.25) | |
| ≥80 | 1,160 (31.99) | 769 (31.20) | 391 (33.68) | |
| No. of diseases [IQR], n (%) | 3 [2, 4] | 0.034 | ||
| 1–2 | 1,166 (32.16) | 821 (33.31) | 345 (29.72) | |
| 3–4 | 1,607 (44.32) | 1,090 (44.22) | 517 (44.53) | |
| ≥5 | 853 (23.52) | 554 (22.47) | 299 (25.75) | |
| No. of medications [IQR], n (%) | 4 [2, 5] | <0.001 | ||
| 1–4 | 2,290 (63.15) | 1,249 (50.67) | 1,041 (89.66) | |
| 5–9 | 1,274 (35.14) | 1,157 (46.94) | 117 (10.08) | |
| ≥10 | 62 (1.71) | 59 (2.39) | 3 (0.26) | |
| Prescription expenditure [IQR], n (%) | 154.45 [58.72, 421.22] | <0.001 | ||
| <500 CNY | 2,828 (77.99) | 1,850 (75.05) | 978 (84.24) | |
| 500–1000 CNY | 407 (11.22) | 309 (12.54) | 98 (8.44) | |
| >1000 CNY | 391 (10.78) | 306 (12.41) | 85 (7.32) | |
| Medicare reimbursement, n (%) | <0.001 | |||
| Non-reimbursement | 1,307 (36.05) | 964 (39.11) | 343 (29.54) | |
| Reimbursement | 2,319 (63.95) | 1,501 (60.89) | 818 (70.46) | |
| Departments, n (%) | <0.001 | |||
| Department of cardiology | 2,522 (69.55) | 1,765 (71.60) | 757 (65.20) | |
| Department of geriatrics | 258 (7.12) | 177 (7.18) | 81 (6.98) | |
| Other departments | 846 (23.33) | 523 (21.22) | 323 (27.82) | |
| Concomitant diseases, n (%) | ||||
| Coronary heart disease | 1,623 (44.76) | 1,097 (44.50) | 526 (45.31) | 0.650 |
| Hypertension | 1,111 (30.64) | 754 (30.59) | 357 (30.75) | 0.922 |
| Atrial fibrillation and atrial flutter | 940 (25.92) | 666 (27.02) | 274 (23.60) | 0.028 |
| Diabetes mellitus | 426 (11.75) | 294 (11.93) | 132 (11.37) | 0.627 |
| Gastritis | 395 (10.89) | 231 (9.37) | 164 (14.13) | <0.001 |
| Myocardiopathy | 325 (8.96) | 236 (9.57) | 89 (7.67) | 0.061 |
| Renal dysfunction | 292 (8.05) | 175 (7.10) | 117 (10.08) | 0.002 |
| Valvular heart disease | 271 (7.47) | 197 (7.99) | 74 (6.37) | 0.084 |
| Chronic obstructive pulmonary disease | 227 (6.26) | 153 (6.21) | 74 (6.37) | 0.847 |
| Insomnia | 222 (6.12) | 177 (7.18) | 45 (3.88) | <0.001 |
PIM, Potentially inappropriate medication; CNY, Chinese Yuan
PIM evaluation
Among the 3,626 prescriptions, 2,465 had at least one PIM. The prevalence rate of PIMs was 67.98%. Of all PIM prescriptions, 39.63% had one PIM, 44.14% had two PIMs, and 16.23% had three or more PIMs. The prevalence of PIMs was shown in Table 2 (page 22, line 423–425).
Table 2.
Prevalence and evaluation of PIM use as identified according to Beers Criteria 2019
| Characteristics | Total (%) |
|---|---|
| PIM prescriptions | 2,465 |
| 1 PIM | 977 (39.63) |
| 2 PIMs | 1,088 (44.14) |
| 3 PIMs | 335 (13.59) |
| 4 PIMs | 60 (2.43) |
| 5 PIMs | 4 (0.16) |
| 6 PIMs | 1 (0.04) |
| PIM items | 4,424 |
| Potentially inappropriate medication use in older adults | 340 (7.69) |
| Potentially inappropriate medication use in older adults due to drug-disease or drug-syndrome interactions that may exacerbate the disease or syndrome | 597 (13.49) |
| Drugs to be used with caution in older adults | 3,478 (78.62) |
| Potentially clinically important drug-drug interactions that should be avoided in older adults | 9 (0.20) |
PIM, Potentially inappropriate medication
The first four types of criteria in the 2019 Beers criteria were used for PIM evaluation. A total of 4,424 PIMs were detected, among which drugs to be used with caution were the most, accounting for 78.62%. The PIM evaluation based on 2019 Beers criteria was shown in Table 2 (page 22–23, line 427–429). Four additional files showed this in more details [see Additional file 1–4].
Most frequent of prescribing PIMs
According to 2019 Beers criteria, the top five PIMs in outpatients with heart failure were diuretics (71.61%), non-steroidal anti-inflammatory drugs (NSAIDs) (13.22%), benzodiazepine receptor agonist hypnotics (4.18%), rivaroxaban (2.89%), and dabigatran (1.60%). Spironolactone (30.56%) was the most common diuretic PIM, followed by furosemide (23.42%). Among NSAIDs and benzodiazepine receptor agonist hypnotics, aspirin (12.70%) and alprazolam (2.26%) were the most common PIMs respectively. The top five PIMs and their corresponding PIM types were showed in Table 3 (page 23–26, line 431–433).
Table 3.
The most common PIMs use in elderly outpatients with heart failure
| Medications | Types of PIMs | N = 4,424 (%) |
|---|---|---|
| Diuretics | 3,168 (71.61) | |
| Spironolactone | Use with caution in older adults | 1,352 (30.56) |
| Furosemide | Use with caution in older adults | 1,036 (23.42) |
| Hydrochlorothiazide | Use with caution in older adults | 454 (10.26) |
| Torasemide | Use with caution in older adults | 321 (7.26) |
| Indapamide | Use with caution in older adults | 5 (0.11) |
| NSAIDs | 585 (13.22) | |
| Use with caution in adults ≥ 70 years for primary prevention of cardiovascular disease and colorectal cancer; | 78 (1.76) | |
| Aspirin | Use in older adults with heart failure; | 482 (10.90) |
| Use in older adults with chronic kidney disease stage 4 or higher | 2 (0.05) | |
| Celecoxib | Use in older adults with heart failure | 5 (0.11) |
| Ibuprofen |
Chronic use of non–cyclooxygenase-selective NSAIDs in older adults without gastroprotective agents; Use in older adults with heart failure |
4 (0.09) |
| Loxoprofen | Use in older adults with heart failure | 2 (0.05) |
| Meloxicam |
Chronic use of non–cyclooxygenase-selective NSAIDs in older adults without gastroprotective agents; Use in older adults with heart failure |
2 (0.05) |
| Nimesulide | Use in older adults with heart failure | 2 (0.05) |
| Sulindac |
Chronic use of non–cyclooxygenase-selective NSAIDs in older adults without gastroprotective agents; Use in older adults with heart failure |
2 (0.05) |
| Diclofenac | Use in older adults with heart failure | 2 (0.05) |
| Etoricoxib | Use in older adults with heart failure | 1 (0.02) |
| Parecoxib | Use in older adults with heart failure | 1 (0.02) |
| Flurbiprofen | Use in older adults with heart failure | 1 (0.02) |
| Imrecoxib | Use in older adults with heart failure | 1 (0.02) |
| Benzodiazepine receptor agonist hypnotics (Benzodiazepines and nonbenzodiazepines) | 185 (4.18) | |
| Alprazolam |
Use of short and intermediate acting benzodiazepines in older adults; Combination of opioids and benzodiazepines; Combination of three or more CNS-active drugs |
100 (2.26) |
| Estazolam |
Use of short and intermediate acting benzodiazepines in older adults; Combination of opioids and benzodiazepines; |
66 (1.49) |
| Eszopiclone | Use of benzodiazepine receptor agonist hypnotics in older adults | 9 (0.20) |
| Clonazepam | Use of long acting benzodiazepines in older adults | 8 (0.18) |
| Zolpidem | Use of benzodiazepine receptor agonist hypnotics in older adults | 1 (0.02) |
| Zaleplon | Use of benzodiazepine receptor agonist hypnotics in older adults | 1 (0.02) |
| Rivaroxaban | Use with caution for treatment of VTE or atrial fibrillation in adults ≥ 75 years | 128 (2.89) |
| Dabigatran | Use with caution for treatment of VTE or atrial fibrillation in adults ≥ 75 years | 71 (1.60) |
PIM, Potentially inappropriate medication; NSAIDs, Non-steroidal anti-inflammatory drugs
Factors associated with PIMs
Based on 2019 Beers criteria, multivariate logistic regression analysis was performed with PIM use as the dependent variable and gender, age, number of diseases, number of medications, prescription expenditure, medicare reimbursement, departments and concomitant diseases as the independent variables. The results showed polypharmacy (5–9 medications, OR: 10.403, 95% CI: 8.258–13.104, p < 0.001; ≥10 medications, OR: 35.018, 95% CI: 10.545-116.293, p < 0.001), valvular heart disease (OR: 1.537, 95% CI: 1.109–2.131, p = 0.010), and insomnia (OR: 2.655, 95% CI: 1.809–3.898, p < 0.001) were positively correlated with PIMs. Compared with department of geriatrics, more PIMs were prescribed by department of cardiology (OR: 1.687, 95% CI: 1.214–2.344, p = 0.002). More diseases (3–4 diseases, OR: 0.723, 95% CI: 0.582–0.897, p = 0.003; ≥5 diseases, OR: 0.513, 95% CI: 0.372–0.706, p < 0.001), reimbursement (OR: 0.678, 95% CI: 0.570–0.808, p < 0.001), gastritis (OR: 0.579, 95% CI: 0.441–0.758, p < 0.001), and renal dysfunction (OR: 0.553, 95% CI: 0.398–0.769, p < 0.001) were negatively correlated with PIMs. Multivariate logistic regression analysis of factors associated with PIMs was showed in Table 4 (page 26–27, line 435–437).
Table 4.
Multivariate logistic regression analysis of factors associated with PIMs
| Characteristics | OR | 95% CI | p value |
|---|---|---|---|
| Gender | |||
| Male | Reference | ||
| Female | 1.221 | 1.044–1.430 | 0.013 |
| Age (Years) | |||
| 65–69 | Reference | ||
| 70–79 | 1.142 | 0.928–1.406 | 0.210 |
| ≥80 | 1.065 | 0.851–1.333 | 0.583 |
| No. of diseases | |||
| 1–2 | Reference | ||
| 3–4 | 0.723 | 0.582–0.897 | 0.003 |
| ≥5 | 0.513 | 0.372–0.706 | p<0.001 |
| No. of medications | |||
| 1–4 | Reference | ||
| 5–9 | 10.403 | 8.258–13.104 | p<0.001 |
| ≥10 | 35.018 | 10.545-116.293 | p<0.001 |
| Prescription expenditure | |||
| <500 CNY | Reference | ||
| 500–1000 CNY | 0.991 | 0.749–1.311 | 0.947 |
| >1000 CNY | 1.018 | 0.745–1.391 | 0.911 |
| Medicare reimbursement | |||
| Non-reimbursement | Reference | ||
| Reimbursement | 0.678 | 0.570–0.808 | p<0.001 |
| Departments | |||
| Department of geriatrics | Reference | ||
| Department of cardiology | 1.687 | 1.214–2.344 | 0.002 |
| Other departments | 1.220 | 0.854–1.743 | 0.275 |
| Concomitant diseases | |||
| Coronary heart disease | 1.018 | 0.846–1.224 | 0.852 |
| Hypertension | 1.158 | 0.945–1.418 | 0.157 |
| Atrial fibrillation and atrial flutter | 1.218 | 0.996–1.488 | 0.054 |
| Diabetes mellitus | 0.901 | 0.686–1.184 | 0.456 |
| Gastritis | 0.579 | 0.441–0.758 | p<0.001 |
| Myocardiopathy | 1.244 | 0.928–1.667 | 0.144 |
| Renal dysfunction | 0.553 | 0.398–0.769 | p<0.001 |
| Valvular heart disease | 1.537 | 1.109–2.131 | 0.010 |
| Chronic obstructive pulmonary disease | 1.156 | 0.824–1.622 | 0.401 |
| Insomnia | 2.655 | 1.809–3.898 | p<0.001 |
PIM, Potentially inappropriate medication; CNY, Chinese Yuan
Discussion
China is a country with a serious aging problem. According to the 2020 census, nearly 14% of Chinese population aged 65 years old and above [16]. Heart failure, a global public health issue, is closely related to population aging, and brings a heavy burden to the older adults [17]. Up to now, there were few studies on PIMs in patients with heart failure. Zahwe et al. used 2015 Beers criteria to investigate PIMs in older outpatients with heart failure who attended cardiology clinics in Lebanon, and the prevalence rate of PIMs was 80% [14]. Jaber et al. assessed PIMs in older patients in the United States who were discharged alive after heart failure hospitalization based on 2019 Beers, and they found the prevalence of PIMs was 61.1% at admission and 64.0% at discharge [15]. Our study found the prevalence rate of PIMs was 67.98% in older outpatients with heart failure in China, which was lower than Lebanon and slightly higher than the United States. All of the three studies showed the high prevalence of PIMs. This could be attributed primarily to medication regimen of heart failure. In addition, the patients’ comorbidities and corresponding medications were also linked to the PIMs use.
Zahwe et al. found diuretics, proton pump inhibitors, benzodiazepines, and dabigatran were the most common PIMs in elderly HF patients [14]. While, in the study of Jaber et al., the most common PIMs were proton pump inhibitors, benzodiazepines, analgesics at hospital admission, and proton pump inhibitors, benzodiazepines, amiodarone at hospital discharge [15]. In our study, the most frequent PIMs in Chinese older outpatients with heart failure were diuretics, NSAIDs, benzodiazepine receptor agonist hypnotics, rivaroxaban, and dabigatran, partially identical to the findings of Zahwe et al. [14]. Among them, diuretics were the vast majority as expected. Furosemide and spironolactone were the most commonly used PIMs, which were also the most commonly used diuretics for heart failure. Diuretic therapy is the cornerstone of heart failure treatment as fluid retention occurs in heart failure, and diuretic therapy could relieve acute congestion and maintain “dry” weight of patients with heart failure [18, 19]. Diuretics are listed as drugs to be used with caution in Beers criteria because they may exacerbate or cause SIADH or hyponatremia [10]. It is suggested that the use of diuretics and the risk of electrolyte disturbance should be well balanced, and electrolytes should be regularly monitored in older adults who use diuretics.
Among NSAIDs, aspirin is the predominant PIM with the use in adults ≥ 70 years for primary prevention of cardiovascular disease. Aspirin use is controversial for primary prevention of atherosclerotic cardiovascular disease (ASCVD) due to the increased risk of bleeding accompanied with the reduced risk of atherothrombosis [20]. ACC/AHA published guideline on the primary prevention of cardiovascular disease in 2019 [21]. They pointed out that prophylactic aspirin was potentially harmful in adults > 70 years old for primary prevention of ASCVD, and given the higher risk of bleeding in this age group [21]. Thus, they suggested that low-dose aspirin (75–100 mg orally daily) should not be administered on a routine basis for the primary prevention of ASCVD among adults > 70 years of age [21]. In addition to prophylactic aspirin, potentially inappropriate use of NSAIDs included the use in old patients with heart failure or chronic kidney disease stage 4 or higher, use of non-selective nonsteroidal anti-inflammatory drugs (NSAIDs) in older adults with history of gastric or duodenal ulcers, and chronic use of non–cyclooxygenase-selective NSAIDs in older adults without gastroprotective agents. NSAIDs could lead to gastrointestinal mucosal injury, renal injury, and exacerbate heart failure [22]. Therefore, it is inappropriate to use NSAIDs in these conditions. Using an alternative to NSAIDs to older adults such as acetaminophen for pain or fever may be a good option.
Insomnia is a prevalent comorbidity of heart failure. More than half of patients with heart failure report insomnia [23]. Benzodiazepine receptor agonist hypnotics, including benzodiazepines and nonbenzodiazepines, are widely used to treat insomnia, and long-term use of them in older adults is prevalent [24–27]. Benzodiazepine receptor agonist hypnotics can lead to serious injuries such as falls, fractures, and traffic accidents [28, 29]. Besides, benzodiazepines are associated with dementia or cognitive impairment [30–32]. These adverse consequences not only bring increased mortality but also put a strain on society’s finances and judicial system. Since the therapeutic effects of benzodiazepine receptor agonist hypnotics might be short-term, but the harms might be serious, older adults should avoid using them, especially long-term use [33]. Currently, some nonpharmacologic alternatives have been proposed for deprescribing benzodiazepine receptor agonists, such as sleep restriction-sleep compression therapy, behavioral management, and cognitive behavioral therapy [33–35].
Rivaroxaban and dabigatran, for long-term treatment of venous thromboembolism and atrial fibrillation, are classified as medications to be used with caution because of the bleeding risk in older adults [10]. Atrial fibrillation is the most common arrhythmia in patients with heart failure, with an average prevalence of 25% [36]. Rivaroxaban and dabigatran are new oral anticoagulants that are preferred by many patients and physicians since they do not require routine coagulation monitoring. However, they have higher risk of gastrointestinal bleeding than warfarin [37, 38]. For older adults ≥ 75 years, the use of rivaroxaban and dabigatran requires caution and close monitoring of bleeding symptoms. Besides, patients with mechanical heart valves and atrial fibrillation may qualify for vitamin K antagonists instead of rivaroxaban or dabigatran.
The result of multivariate logistic regression analysis showed that patients with polypharmacy, and combined with valvular heart disease or insomnia on the basis of heart failure were more likely to be prescribed PIMs. Compared with patients prescribed one to four medications, patients prescribed five to nine medications had more than ten times the risk of PIMs use, and patients prescribed ten medications and above had more than thirty-five times the risk of PIMs use. Polypharmacy is the most important risk factor for PIMs use, which is not limited to patients with heart failure [39–41]. In our study, the prevalence of polypharmacy was 36.85% in patients with heart failure, similar to the results of studies conducted by Niriayo et al. (37.9%) and Wu et al. (37.5%) [42, 43]. Heart failure and atrial fibrillation are prevalent in valvular heart diseases, leading to more use of diuretics and anticoagulants (including rivaroxaban and dabigatran) [44, 45]. Benzodiazepine receptor agonist hypnotics make great contributions to the treatment of insomnia [24–27]. The above reasons might make valvular heart disease and insomnia the risk factors of PIMs use in our study. On the other part, we found ≥ 3 diseases, medicare reimbursement were negatively correlated with PIMs. Since diuretics, NSAIDs, and anticoagulants prescribed in patients with heart failure led to PIMs use, and some comorbidities (gastritis and renal dysfunction) were protective factors, it was concluded that more diseases were negatively associated with PIMs use. This might indicate that heart failure was a risk factor of PIMs use. Absence of reimbursement is a barrier to polypharmacy management [46]. Medicare reimbursement helps reduce polypharmacy, thus decreasing PIMs use. In addition, fewer PIMs were prescribed in the geriatric department than in the cardiology department. This suggests that physicians of geriatric department may pay more attention to polypharmacy and PIMs in older patients. They may be more cautious when prescribing medications, hence PIMs use is lower.
Polypharmacy and PIMs use are common in older adults, which may become more prominent due to the poor health of older adults after the COVID-19 pandemic [47, 48]. In recent years, a variety of interventions have been proposed to reduce PIMs in older adults, such as medication review, Clinical Decision Support System, educational interventions, multifaceted approaches, and organizational strategies [49]. However, no matter which intervention is used, clinical multidisciplinary teams are required to collaborate in patient medication management.
There were some limitations in this study. First, this was a retrospective study in one area of China, which produced selection bias in the results. The results need to be further confirmed by including more regions. Second, this study focused on patients in tertiary medical institutions, where patients with complex conditions and therapies were admitted. The results could not reflect PIMs use in primary hospitals. Third, this study included only outpatients, which could not reflect PIMs use in hospitalized patients. Fourth, medications that should be avoided or have their dosage reduced with varying levels of kidney function in older adults were not evaluated. Fifth, follow-up data were not available to investigate the association between PIMs and adverse clinical outcomes in this study. Finally, we used the 2019 Beers criteria and not the updated 2023 criteria.
Conclusions
This study investigated the prevalence and risk factors of PIMs in older outpatients with heart failure in Chengdu. The results showed that the prevalence of PIMs was high, and polypharmacy, atrial fibrillation/atrial flutter, valvular heart disease, insomnia were the risk factors. PIMs use is common in old patients, and medication review is important. Deprescribing strategies reduce PIMs use and improve the quality of life for the elderly. The deprescribing process should be emphasized in every follow-up visit. The management of PIMs is not only the responsibility of physicians or pharmacists. Multidisciplinary teams should work together to manage medications in the older patients to reduce PIMs use.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Acknowledgements
We thank the participants in our study.
Abbreviations
- PIM
Potentially inappropriate medication
- SD
Standard deviation
- IQR
Interquartile range
- CNY
Chinese Yuan
- NSAIDs
Non-steroidal anti-inflammatory drugs
- SIADH
Syndrome of inappropriate antidiuretic hormone
- ASCVD
Atherosclerotic cardiovascular disease
Author contributions
Developing design: Y Zhang, FY Tian; Literature search: Y Zhang, FY Tian, ZY Chen; Manuscript writing: Y Zhang, FY Tian; Analysis of results: Y Zhang, FY Tian, ZY Chen. All authors read and approved the final manuscript.
Funding
This work was supported by National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University (Z2024YY003), 1·3·5 project for disciplines of excellence–Clinical Research Fund, West China Hospital, Sichuan University (2024HXFH015), the Research Project established by Chinese Pharmaceutical Association Hospital Phamacy Department (CPA-Z05-ZC-2024002) and National Key Clinical Specialties Construction Program.
Data availability
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
Declarations
Ethics approval and consent to participate
This study was approved by the West China Hospital Research Ethics Board. All procedures performed in this study conform to the standards of the 1964 Helsinki Declaration and subsequent relevant ethics. Due to the nature of this retrospective study and the preserved anonymity of patients, a waiver of informed consent was obtained by the West China Hospital Research Ethics Board.
Consent for publication
Not applicable.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
References
- 1.Ailabouni NJ, Marcum ZA, Schmader KE, Gray SL. Medication Use Quality and Safety in older adults: 2019 update. J Am Geriatr Soc. 2021;69(2):336–41. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Xing XX, Zhu C, Liang HY, Wang K, Chu YQ, Zhao LB, et al. Associations between potentially inappropriate medications and adverse Health outcomes in the Elderly: a systematic review and Meta-analysis. Ann Pharmacother. 2019;53(10):1005–19. [DOI] [PubMed] [Google Scholar]
- 3.Díez R, Cadenas R, Susperregui J, Sahagún AM, Fernández N, García JJ, et al. Potentially inappropriate medication and polypharmacy in nursing home residents: a cross-sectional study. J Clin Med. 2022;11(13):3808. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Motter FR, Fritzen JS, Hilmer SN, Paniz ÉV, Paniz VMV. Potentially inappropriate medication in the elderly: a systematic review of validated explicit criteria. Eur J Clin Pharmacol. 2018;74(6):679–700. [DOI] [PubMed] [Google Scholar]
- 5.Schiavo G, Forgerini M, Lucchetta RC, Silva GO, Mastroianni PDC. Cost of adverse drug events related to potentially inappropriate medication use: a systematic review. J Am Pharm Assoc. 2022;62(5):1463–76. [DOI] [PubMed] [Google Scholar]
- 6.Morin L, Laroche ML, Texier G, Johnell K. Prevalence of potentially inappropriate medication use in older adults living in nursing homes: a systematic review. J Am Med Dir Assoc. 2016;17(9):e8621–9. [DOI] [PubMed] [Google Scholar]
- 7.Praxedes MFDS, Pereira GCDS, Lima CFDM, Santos DBD, Berhends JS. Prescribing potentially inappropriate medications for the elderly according to Beers Criteria: systematic review. Cien Saude Colet. 2021;26(8):3209–19. [DOI] [PubMed] [Google Scholar]
- 8.Alshammari H, Al-Saeed E, Ahmed Z, Aslanpour Z. Reviewing potentially inappropriate medication in hospitalized patients over 65 using Explicit Criteria: a systematic literature review. Drug Healthc Patient Saf. 2021;13:183–210. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Schiavo G, Forgerini M, Lucchetta RC, Mastroianni PC. A comprehensive look at explicit screening tools for potentially inappropriate medication: a systematic scoping review. Australas J Ageing. 2022;41(3):357–82. [DOI] [PubMed] [Google Scholar]
- 10.The 2019 American Geriatrics Society Beers Criteria® Update Expert Panel. American Geriatrics Society 2019 Updated AGS Beers Criteria® for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2019;67(4):674–94. [DOI] [PubMed] [Google Scholar]
- 11.Dharmarajan K, Rich MW. Epidemiology, pathophysiology, and prognosis of Heart failure in older adults. Heart Fail Clin. 2017;13(3):417–26. [DOI] [PubMed] [Google Scholar]
- 12.Abete P, Testa G, Della-Morte D, Gargiulo G, Galizia G, de Santis D, et al. Treatment for chronic heart failure in the elderly: current practice and problems. Heart Fail Rev. 2013;18(4):529–51. [DOI] [PubMed] [Google Scholar]
- 13.Butrous H, Hummel SL. Heart failure in older adults. Can J Cardiol. 2016;32(9):1140–7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Zahwe M, Skouri H, Rachidi S, Khoury M, Noureddine S, Isma’eel H, et al. Potentially inappropriate medications in elderly patients with heart failure: Beers Criteria-based study. Int J Pharm Pract. 2020;28(6):652–9. [DOI] [PubMed] [Google Scholar]
- 15.Jaber D, Vargas F, Nguyen L, Ringel J, Zarzuela K, Musse M, et al. Prescriptions for potentially inappropriate medications from the Beers Criteria among older adults hospitalized for heart failure. J Card Fail. 2022;28(6):906–15. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Jiang Q, Feng Q, Editorial. Aging and health in China. Front Public Health. 2022;10:998769. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Yan T, Zhu S, Yin X, Xie C, Xue J, Zhu M, et al. Burden, Trends, and inequalities of heart failure globally, 1990 to 2019: a secondary analysis based on the global burden of Disease 2019 study. J Am Heart Assoc. 2023;12(6):e027852. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Felker GM, Ellison DH, Mullens W, Cox ZL, Testani JM. Diuretic therapy for patients with heart failure: JACC state-of-the-art review. J Am Coll Cardiol. 2020;75(10):1178–95. [DOI] [PubMed] [Google Scholar]
- 19.Sica DA, Gehr TWB, Frishman WH. Use of diuretics in the treatment of Heart failure in older adults. Heart Fail Clin. 2017;13(3):503–12. [DOI] [PubMed] [Google Scholar]
- 20.Soodi D, VanWormer JJ, Rezkalla SH. Aspirin in primary Prevention of Cardiovascular events. Clin Med Res. 2020;18(2–3):89–94. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Arnett DK, Blumenthal RS, Albert MA, Buroker AB, Goldberger ZD, Hahn EJ, et al. 2019 ACC/AHA Guideline on the primary Prevention of Cardiovascular Disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice guidelines. J Am Coll Cardiol. 2019;74(10):e177–232. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Bindu S, Mazumder S, Bandyopadhyay U. Non-steroidal anti-inflammatory drugs (NSAIDs) and organ damage: a current perspective. Biochem Pharmacol. 2020;180:114147. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Gharzeddine R, McCarthy MM, Yu G, Dickson VV. Insomnia and insomnia symptoms in persons with heart failure: an integrative review. J Cardiovasc Nurs. 2021;36(4):374–84. [DOI] [PubMed] [Google Scholar]
- 24.Okui T, Park J, Hirata A, Nakashima N. Trends in the prescription of benzodiazepine receptor agonists from 2009 to 2020: a retrospective study using Electronic Healthcare Record Data of a University Hospital in Japan. Healthcare. 2021;9(12):1724. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.Minns AB, Kreshak A, Dunlay R, Castillo E, Clark RF, Killeen J, et al. Prevalence of benzodiazepine and benzodiazepine-receptor agonist use in a geriatric Emergency Department Population. J Am Geriatr Soc. 2019;67(6):1309–11. [DOI] [PubMed] [Google Scholar]
- 26.Avidan AY, Palmer LA, Doan JF, Baran RW. Insomnia medication use and the probability of an accidental event in an older adult population. Drug Healthc Patient Saf. 2010;2:225–32. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Weir DL, Samanani S, Gilani F, Jess E, Eurich DT. Benzodiazepine receptor agonist dispensations in Alberta: a population-based descriptive study. CMAJ Open. 2018;6(4):E678–84. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Madhusoodanan S, Bogunovic OJ. Safety of benzodiazepines in the geriatric population. Expert Opin Drug Saf. 2004;3(5):485–93. [DOI] [PubMed] [Google Scholar]
- 29.Treves N, Perlman A, Kolenberg Geron L, Asaly A, Matok I. Z-drugs and risk for falls and fractures in older adults-a systematic review and meta-analysis. Age Ageing. 2018;47(2):201–8. [DOI] [PubMed] [Google Scholar]
- 30.Lucchetta RC, da Mata BPM, Mastroianni PC. Association between Development of Dementia and Use of benzodiazepines: a systematic review and Meta-analysis. Pharmacotherapy. 2018;38(10):1010–20. [DOI] [PubMed] [Google Scholar]
- 31.Crowe SF, Stranks EK. The residual medium and long-term Cognitive effects of Benzodiazepine Use: an updated Meta-analysis. Arch Clin Neuropsychol. 2018;33(7):901–11. [DOI] [PubMed] [Google Scholar]
- 32.Picton JD, Marino AB, Nealy KL. Benzodiazepine use and cognitive decline in the elderly. Am J Health Syst Pharm. 2018;75(1):e6–12. [DOI] [PubMed] [Google Scholar]
- 33.Pottie K, Thompson W, Davies S, Grenier J, Sadowski CA, Welch V, et al. Deprescribing benzodiazepine receptor agonists: evidence-based clinical practice guideline. Can Fam Physician. 2018;64(5):339–51. [PMC free article] [PubMed] [Google Scholar]
- 34.Lee JY, Farrell B, Holbrook AM. Deprescribing benzodiazepine receptor agonists taken for insomnia: a review and key messages from practice guidelines. Pol Arch Intern Med. 2019;129(1):43–9. [DOI] [PubMed] [Google Scholar]
- 35.Markota M, Rummans TA, Bostwick JM, Lapid MI. Benzodiazepine Use in Older Adults: Dangers, Management, and Alternative Therapies. Mayo Clin Proc. 2016;91(11):1632–1639. [DOI] [PubMed]
- 36.Carlisle MA, Fudim M, DeVore AD, Piccini JP. Heart failure and Atrial Fibrillation, like fire and fury. JACC Heart Fail. 2019;7(6):447–56. [DOI] [PubMed] [Google Scholar]
- 37.Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365(10):883–91. [DOI] [PubMed] [Google Scholar]
- 38.Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361(12):1139–51. [DOI] [PubMed] [Google Scholar]
- 39.Bhagavathula AS, Gebreyohannes EA, Fialova D. Prevalence of polypharmacy and risks of potentially inappropriate medication use in the older Population in a developing country: a systematic review and Meta-analysis. Gerontology. 2022;68(2):136–45. [DOI] [PubMed] [Google Scholar]
- 40.Storms H, Marquet K, Aertgeerts B, Claes N. Prevalence of inappropriate medication use in residential long-term care facilities for the elderly: a systematic review. Eur J Gen Pract. 2017;23(1):69–77. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 41.Tian F, Chen Z, Zeng Y, Feng Q, Chen X. Prevalence of Use of potentially inappropriate medications among older adults Worldwide: a systematic review and Meta-analysis. JAMA Netw Open. 2023;6(8):e2326910. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 42.Niriayo YL, Kumela K, Kassa TD, Angamo MT. Drug therapy problems and contributing factors in the management of heart failure patients in Jimma University Specialized Hospital, Southwest Ethiopia. PLoS ONE. 2018;13(10):e0206120. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 43.Wu Y, Zhu W, He X, Xue R, Liang W, Wei F, et al. Influence of polypharmacy on patients with heart failure with preserved ejection fraction: a retrospective analysis on adverse outcomes in the TOPCAT trial. Br J Gen Pract. 2020;71(702):e62–70. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 44.Marciniak A, Glover K, Sharma R. Cohort profile: prevalence of valvular heart disease in community patients with suspected heart failure in UK. BMJ Open. 2017;7(1):e012240. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 45.John B, Lau CP. Atrial fibrillation in Valvular Heart Disease. Card Electrophysiol Clin. 2021;13(1):113–22. [DOI] [PubMed] [Google Scholar]
- 46.Whitman A, Erdeljac P, Jones C, Pillarella N, Nightingale G. Managing polypharmacy in older adults with Cancer across different Healthcare settings. Drug Healthc Patient Saf. 2021;13:101–16. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 47.Tian F, Chen Z, Feng Q. Nirmatrelvir-ritonavir compared with other antiviral drugs for the treatment of COVID-19 patients: a systematic review and meta-analysis. J Med Virol. 2023;95(4):e28732. [DOI] [PubMed] [Google Scholar]
- 48.Tian F, Feng Q, Chen Z. Efficacy and safety of Molnupiravir Treatment for COVID-19: a systematic review and Meta-analysis of Randomized controlled trials. Int J Antimicrob Agents. 2023;62(2):106870. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 49.Rodrigues DA, Plácido AI, Mateos-Campos R, Figueiras A, Herdeiro MT, Roque F. Effectiveness of interventions to reduce potentially inappropriate medication in older patients: a systematic review. Front Pharmacol. 2022;12:777655. [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.