Potentially inappropriate medications in older Chinese outpatients based on the Beers criteria and Chinese criteria

doi:10.21203/rs.3.rs-1604214/v1

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Potentially inappropriate medications in older Chinese outpatients based on the Beers criteria and Chinese criteria

https://doi.org/10.21203/rs.3.rs-1604214/v1

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Objective

Polypharmacy increases the prevalence of potentially inappropriate drugs (PIMs) among older persons, lowering their quality of life. This study aimed to compare the prevalence of PIMs in older Chinese outpatients according to the Beers criteria and the Chinese criteria and to analyze the risk factors. Second, we describe the differences between the two criteria, focusing on the inappropriate prescription of drugs in older outpatients.

Methods

In Chengdu, Southwest China, a retrospective study was undertaken using electronic medical data from 9 medical institutions. Outpatients above the age of 60 who were treated in the Geriatrics Center of these medical institutions were included. The Beers criteria and the Chinese criteria were used to evaluate the PIM status of older outpatients, and logistic regression was used to identify potential risk factors for PIMs.

Results

There were 44,458 prescriptions from 2016 to 2018. The prevalence of PIMs among older outpatients was 30.05% (according to the Beers criteria) and 35.38% (according to the Chinese criteria). Estazolam, hydrochlorothiazide and alprazolam were the top three PIMs in the Beers criteria, while the top three PIMs in the Chinese criteria were clopidogrel, estazolam and insulin. The prevalence of PIMs was associated with age, the number of diseases and the number of drugs. PIMs were shown to be more common in patients aged 70 and above, with more than 2 kinds of diseases and more than 4 kinds of drugs.

Conclusion

PIMs were shown to be common among older outpatients in China, according to this study. The detection rate of the Chinese criteria was higher than that of the Beers criteria.

Older age

potentially inappropriate medications

Beers criteria

Chinese criteria

outpatient

Aim: To compare PIMs in older Chinese outpatients according to the Beers criteria and the Chinese criteria and to analyze the risk factors.

Findings: The prevalence of PIMs based on Chinese criteria is higher than that based on Beers criteria. Benzodiazepines were highly frequent PIMs. Being ≥70 years old, having ≥3 diseases, and taking ≥5 drugs were the common risk factors.

Message: PIMs were shown to be common among older outpatients in China. Doctors and pharmacists should cooperate to reduce PIMs in older adults.

Comorbidity and polypharmacy in older persons are becoming more common as global aging becomes more serious. Polypharmacy is widespread in older adults, although it is not always avoided. It frequently involves inappropriate medications and can result in negative health effects.¹ Alterations in age-related pharmacokinetics and pharmacodynamics predispose older adults to drug-related problems, such as adverse drug reactions (ADRs), drug–drug interactions or drug-disease interactions. These adverse events often reduce the quality of life of older adults, increase the hospitalization rate and disability rate, and increase the economic burden on the social medical system.^2–4 Thus, polypharmacy is becoming a major concern, particularly the potentially inappropriate medications (PIMs) that it leads to.

Potentially inappropriate medication is used when the actual or potential harms of therapy outweigh its benefits.⁵ More adverse drug events, longer hospital stays, more resource use, higher hospital readmission rates and higher health-care expenses are all linked to PIMs.^6–12

Different screening tools are available to assess the level of PIMs in older patients. The most extensively used and cited tools for PIMs were the Beers criteria published in the USA.¹³ Criteria of potentially inappropriate medications for older adults in China (the Chinese criteria) proposed by an expert panel were published in 2017, including medication risk and medication risk under morbid state.¹⁴

To date, no studies have reported the differences in the prevalence of PIMs in Chinese outpatients using the Beers criteria and the Chinese criteria. In addition, no studies have analyzed the prevalence and risk factors for PIMs in older Chinese outpatients for three consecutive years. The objectives of this study were to 1) compare the prevalence of PIMs in older Chinese outpatients using the Beers criteria and the Chinese criteria for three consecutive years; 2) investigate relevant risk factors for PIMs; and 3) list the top drugs discovered using the two sets of criteria.

2.1 | Sample and data collection

The prescriptions in this study were from the hospital prescription analytic cooperation project, which was organized by the Chinese Pharmaceutical Association. The hospitals included in the project were voluntary participants. Through the network system, a computer was used to extract prescriptions from hospitals that volunteered to participate in the project. The data extraction rules of the project were that prescriptions of each hospital were randomly selected for 3 ~ 4 days every month, and a total of 40 days of prescriptions were randomly selected in one year. The year of the prescriptions in the project was from 2016 to 2018. In Chengdu, nine hospitals volunteered to participate in the project. All nine hospitals were tertiary medical institutions rather than community service centers. Prescriptions of outpatients aged 60 and above were randomly selected from geriatric departments of the nine hospitals in Chengdu from January 1, 2016, to December 31, 2018. All the information extracted from the computer included the year of prescription, prescription code, drug name, drug specification, administration route, drug price, dosing frequency, dosage, gender, age, and clinical diagnosis. The identities of the hospitals and patients were kept confidential. One prescription had one prescription code, and one prescription code represented one patient.

2.2 | Data inclusion criteria and evaluation criteria

From January 1, 2016 to December 31, 2018, outpatients aged 60 and above in the geriatric department or geriatrics center were included. Prescriptions with missing or incomplete information were excluded, such as gender, diagnosis, drug, and dosage. The prescription was also ruled out if the patient's gender was uncertain. When calculating the number of drugs, solvent substances such as water for injection and 0.9% sodium chloride were not included.

2.3 | Evaluation of PIMs

The 2019 Beers criteria and the 2017 Chinese criteria were used to evaluate the PIMs of older patients. The 2019 Beers criteria included potentially inappropriate medication use in older adults, potentially inappropriate medication use in older adults due to drug-disease or drug-syndrome interactions that may exacerbate the disease or syndrome, drugs to be used with caution in older adults, potentially clinically important 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.¹³ The 2017 Chinese criteria included potentially inappropriate medication use in older adults and potentially inappropriate medication use in older adults in a state of disease or syndrome.¹⁴ Because the patients' creatinine clearance rates could not be available, we did not assess medications that should be avoided or have their dosage reduced with varying levels of kidney function in older adults. As a result, this study mainly studied the first four groups of the 2019 Beers criteria and the two groups of the 2017 Chinese criteria.

2.4 | Statistical analysis

The chi-square test was used to analyze the differences in the characteristics. According to the prescription information extracted, sex, age, number of diseases and number of drugs were included in the multivariate logistic regression analysis to assess the possible risk factors affecting PIMs in older outpatients. A P value of < 0.05 was considered to be statistically significant. SPSS version 26.0 software was used to perform the statistical analysis.

2.5 | Ethics approval

This study protocol was approved by the Sichuan University West China Hospital Research Ethics Board. The informed consent is waived by the ethics committee of Sichuan University West China Hospital Research Ethics Board. All procedures performed in this study conformed to the standards of the 1964 Helsinki Declaration and subsequent relevant ethics.

3.1 | Basic characteristics of patients

From 2016 to 2018, a total of 44,857 prescriptions were acquired. Among them, 312 prescriptions with no diagnosis, 77 prescriptions with incomplete diagnosis, 4 prescriptions with missing gender, and 6 prescriptions with only the water for injection were excluded. Finally, 44,458 prescriptions were included. There were 27,358 prescriptions for male patients, representing 61.54% of the total, and 17,100 prescriptions for female patients, accounting for 38.46%. Patients ranged in age from 60 to 119 years old. The number of drugs ranged from 1 to 24, while the number of diseases ranged from 1 to 19. The basic characteristics of the patients are listed in Table 1.

3.2 | Detection of PIMs

According to the Beers criteria, 13,358 (30.05%) of the 44,458 prescriptions had at least one PIM. According to the Chinese criteria, 15,728 prescriptions (35.38%) contained at least one PIM. The prevalence rates of PIMs are listed in Table 2. Estazolam, hydrochlorothiazide and alprazolam were the top three PIMs in the Beers criteria, while clopidogrel, estazolam and insulin were the top three PIMs in the Chinese criteria. The top ten PIMs are listed in Table 3.

3.3 | Factors associated with PIMs

From the extracted prescription information, sex, age, number of diseases and number of drugs were included in multivariate logistic regression analysis. The reference groups were males, 60 ~ 69 years old, 1 ~ 2 kinds of diseases and 1 ~ 4 kinds of drugs. According to the Beers criteria, gender, age, the number of diseases and the number of drugs all affected the prevalence of PIMs. PIMs were more common in patients who were female (OR 1.359, 95% CI 1.301 ~ 1.421), aged 70 and above (OR 1.125, 95% CI 1.065 ~ 1.189), had more than 2 kinds of diseases (OR 1.315, 95% CI 1.245 ~ 1.389), and had more than 4 kinds of drugs (OR 2.709, 95% CI 2.566 ~ 2.859). According to the Chinese criteria, age, the number of diseases and the number of drugs were all linked to an increased risk of PIM use. PIMs were more common in patients aged 70 and above (OR 1.131 95% CI 1.071 ~ 1.195), as well as those with more than 2 kinds of diseases (OR 1.656, 95% CI 1.570 ~ 1.747) and more than 4 kinds of drugs (OR 4.333, 95% CI 4.101 ~ 4.578). Patients who took more than 9 kinds of drugs had the highest risk of PIM use, according to both criteria, as shown in Table 4.

There are four major findings in our study: 1) The Chinese criteria revealed a higher prevalence of PIMs in older Chinese outpatients (35.38%) than the Beers criteria (30.05%). 2) The prevalence of PIMs in older Chinese outpatients gradually increased over three consecutive years, regardless of the Chinese criteria or Beers criteria. 3) Estazolam was the most common PIM according to the Beers criteria, while clopidogrel was the most common PIM according to the Chinese criteria. 4) Patients aged 70 and above, with more than 2 kinds of diseases, and with more than 4 kinds of drugs were the common risk factors according to two sets of criteria.

Other studies showed that the prevalence of PIMs in older outpatients ranged from 32.16–64.80% based on the same version of the Beers criteria.^15–22 In our study, the prevalence of PIMs based on the Beers criteria was lower than that based on the Chinese criteria. This might be because the medications in the two criteria differed. In China, some of the medications listed in the Beers criteria were not available. Furthermore, the Chinese criteria were biased because they were designed for Chinese patients. At the same time, we found that the prevalence of PIMs in older Chinese outpatients increased gradually from 2016 to 2018, regardless of whether the Chinese criteria or the Beers criteria were used. As a result, enhancing the sensible use of medications in older Chinese outpatients to reduce PIMs remains a major challenge.

Estazolam, hydrochlorothiazide and alprazolam were the top three PIMs in the Beers criteria, while clopidogrel, estazolam and insulin were the top three PIMs in the Chinese criteria. The difference in results was primarily attributable to the disparity between the two criteria. Diuretics were included in the Beers criteria as drugs to be used with caution in older adults due to the risk of hyponatremia, and regular monitoring of sodium was recommended when starting or altering dosages in older adults.^23–27 Diuretics were excluded from the Chinese criteria; however, clopidogrel was included because of the hematologic and neurological adverse reactions associated with clopidogrel.^28–32 On the other hand, the Beers criteria did not include clopidogrel. Despite the fact that insulin was included in both criteria, there were still discrepancies. The Beers criteria only included short- or rapid-acting insulins that were not used in conjunction with basal or long-acting insulins, while the Chinese criteria included all insulins. This led to a dramatic increase in the detection of insulins as PIMs.

Estazolam and alprazolam, both benzodiazepines, were highly frequent PIMs according to the Beers criteria and the Chinese criteria. Some studies have shown that benzodiazepines are commonly used in older adults, and there is a long-term use phenomenon.^33–35 Benzodiazepines can lead to serious injuries such as falls, fractures, cognitive impairment and car accidents, putting a strain on society's finances and judicial system.^36–37 Older adults are at risk from long-term benzodiazepine use. In addition, studies have shown that benzodiazepines are linked to the development of dementia or cognitive impairment;^38–40 thus, patients with dementia or cognitive impairment should avoid taking them. Regarding the risks associated with benzodiazepines in older adults, several alternative therapies have been proposed to reduce their use.⁴¹

Potentially independent factors associated with PIMs were identified as patients aged 70 and above, with more than 2 kinds of diseases, and with more than 4 kinds of drugs (P < 0.001). Patients who took more than 9 kinds of drugs had the highest risk of PIM use. Polypharmacy was linked to not only PIMs but also medication compliance. Age, medication classes and medication knowledge were found to be associated with medication compliance in a Chinese study of older adults with polypharmacy.¹⁶

The limitations of this study were as follows: 1) This study was a retrospective study including only the outpatients of certain departments in a specific region of China, so the results could not be applied to other countries. 2) Prescriptions were only extracted for 40 days in one year, which did not represent the whole year. 3) The adverse outcomes caused by PIMs were not available, so we could not determine which criteria were more suitable for the evaluation of PIMs.

This study showed that the prevalence of PIMs according to the Chinese criteria was higher than that according to the Beers criteria. The prevalence of PIMs in older Chinese outpatients gradually increased from 2016 to 2018, and benzodiazepines were the most common PIMs. In view of this, we suggest that doctors and pharmacists cooperate to identify the indications of drugs, improve patient compliance, and reduce PIMs in older adults.

Acknowledgments

We thank the participants in our study.

Funding

No funding was received for conducting this study.

Statements and Declarations

Competing Interests

The authors have no competing interests to declare that they are relevant to the content of this article.

Data Availability Statement

The datasets used and/or analysed during the current study available from the corresponding author on reasonable request.

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.

ORCID

Ying Zhang^iD https://orcid.org/0000-0003-1257-7520

Fangyuan Tian^iD https://orcid.org/0000-0002-5187-0386

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T A B L E 1 Basic characteristics of patients

Characteristics	Total(N)	Beers criteria			Chinese criteria
Characteristics	Total(N)	Non-PIM(N)	PIM(N)	P-value	Non-PIM(N)	PIM(N)	P-value
Sex				＜.001			＜.001
Male	27,358	19,402	7,956		17,188	10,170
Female	17,100	11,698	5,402		11,542	5,558
Age (Years)				＜.001			＜.001
60~69	15,109	11,515	3,594		11,204	3,905
70~79	12,958	9,455	3,503		9,006	3,952
≥80	16,391	10,130	6,261		8,520	7,871
Number of diseases				＜.001			＜.001
1~2	29,311	21,702	7,609		21,171	8,140
3~4	8,244	5,532	2,712		4,881	3,363
≥5	6,903	3,866	3,037		2,678	4,225
Number of drugs				＜.001			＜.001
1~4	35,147	26,732	8,415		25,964	9,183
5~9	7,969	4,066	3,903		2,663	5,306
≥10	1,342	302	1,040		103	1,239
Total	44,458	31,100	13,358		28,730	15,728

T A B L E 2 Prevalence of PIMs based on the two criteria

Year	Total (N)	PIM
Year	Total (N)	Beers criteria (N, %)	Chinese criteria (N, %)
2016	15,810	4,343 (27.47%)	5,326 (33.69%)
2017	13,128	4,152 (31.63%)	4,822 (36.73%)
2018	15,520	4,863 (31.33%)	5,580 (35.95%)
Total	44,458	13,358 (30.05%)	15,728 (35.38%)

T A B L E 3 Top ten PIMs based on the two criteria

Beers criteria (N=13,358)
Drugs	Year			Total
Drugs	2016（N=4,343）	2017（N=4,152）	2018（N=4,863）	Total
Estazolam	1,108 (25.51%)	1,260 (30.35%)	1,585 (32.59%)	3,953（29.59%）
Hydrochlorothiazide	823 (18.95%)	652 (15.70%)	786 (16.16%)	2,261（16.93%）
Alprazolam	446 (10.27%)	578 (13.92%)	692 (14.23%)	1,716（12.85%）
Aspirin for primary prevention of cardiovascular disease	366 (8.43%)	300 (7.23%)	286 (5.88%)	952（7.13%）
Chlorpheniramine	356 (8.20%)	259 (6.24%)	324 (6.66%)	939（7.03%）
Spironolactone	271 (6.24%)	261 (6.29%)	292 (6.00%)	824（6.17%）
Glimepiride	386 (8.89%)	275 (6.62%)	97 (1.99%)	758（5.67%）
Furosemide	190 (4.37%)	180 (4.34%)	216 (4.44%)	586（4.39%）
Dexzopiclone	85 (1.96%)	137 (3.30%)	183 (3.76%)	405（3.03%）
Paroxetine	110 (2.53%)	128 (3.08%)	141 (2.90%)	379（2.84%）
Chinese criteria (N=15,728)
Drugs	Year			Total
Drugs	2016 (N=5,326)	2017 (N=4,822)	2018 (N=5,580)	Total
Clopidogrel	1,741 (32.69%)	1,708 (35.42%)	1,945 (34.86%)	5,394（34.30%）
Estazolam	1,108 (20.80%)	1,260 (26.13%)	1,585 (28.41%)	3,953（25.13%）
Insulin	1,145 (21.50%)	799 (16.57%)	841 (15.07%)	2,785（17.71%）
Alprazolam	446 (8.37%)	578 (11.99%)	692 (12.40%)	1,716（10.91%）
Theophylline	442 (8.30%)	400 (8.30%)	501 (8.98%)	1,343（8.54%）
Chlorpheniramine	356 (6.68%)	259 (5.37%)	324 (5.81%)	939（5.97%）
Nicergoline	164 (3.08%)	165 (3.42%)	139 (2.49%)	468（2.98%）
Aspirin for renal insufficiency	149 (2.80%)	134 (2.78%)	124 (2.22%)	407（2.59%）
Diclofenac	73 (1.37%)	107 (2.22%)	79 (1.42%)	259（1.65%）
Olanzapine	88 (1.65%)	87 (1.80%)	82 (1.47%)	257（1.63%）

T A B L E 4 Multivariate logistic regression analysis for PIMs

Characteristics	Beers criteria			Chinese criteria
Characteristics	OR	95%CI	P-value	OR	95%CI	P-value
Sex
Male	Reference			Reference
Female	1.359	1.301~1.421	＜.001	1.017	0.972~1.063	0.471
Age (Years)
60~69	Reference			Reference
70~79	1.125	1.065~1.189	＜.001	1.131	1.071~1.195	＜.001
≥80	1.411	1.336~1.490	＜.001	1.491	1.412~1.574	＜.001
Number of diseases
1~2	Reference			Reference
3~4	1.315	1.245~1.389	＜.001	1.656	1.570~1.747	＜.001
≥5	1.238	1.162~1.320	＜.001	1.984	1.860~2.115	＜.001
Number of drugs
1~4	Reference			Reference
5~9	2.709	2.566~2.859	＜.001	4.333	4.101~4.578	＜.001
≥10	9.295	8.121~10.640	＜.001	23.254	18.935~28.558	＜.001

No competing interests reported.

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Potentially inappropriate medications in older Chinese outpatients based on the Beers criteria and Chinese criteria

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Abstract

Objective

Methods

Results

Conclusion

Key Summary Points

1 | Introduction

2 | Methods

2.1 | Sample and data collection

2.2 | Data inclusion criteria and evaluation criteria

2.3 | Evaluation of PIMs

2.4 | Statistical analysis

2.5 | Ethics approval

3 | Results

3.1 | Basic characteristics of patients

3.2 | Detection of PIMs

3.3 | Factors associated with PIMs

4 | Discussion

5 | Conclusion

Declarations

References

Tables

Additional Declarations

Supplementary Files

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