Abstract
This study aimed to determine the policy implications for drug management by identifying the prescription trends of potentially inappropriate medications (PIMs) in older outpatients. Considering the Drug Utilization Review and Korean version of the standards for PIMs based on the Beers Criteria, 141 ingredients were selected that spanned over 7 years of health insurance claims data analysis. During the study period, the number of patients and claims related to PIMs increased. Although the number of health insurance claims decreased in 2020 owing to coronavirus disease (COVID-19), it increased again in 2021. Tamsulosin was the most frequently prescribed drug for male patients, followed by alprazolam and zolpidem. For female patients, eperisone was the most frequently prescribed drug, followed by alprazolam, zolpidem, and etizolam. In Korea, health insurance claims for PIMs decreased in 2020 owing to the COVID-19 pandemic. However, an overall increasing trend was observed from 2015 to 2021. Moreover, during this period, the prescription trend of benzodiazepine-type drugs and zolpidem increased in both male and female patients. Therefore, management policies regarding PIMs and drug ingredients, such as benzodiazepines and zolpidem, are required.
Keywords: beers criteria, health insurance review and assessment, Korean, older outpatient, potentially inappropriate medication
1. Introduction
In 2020, the United Nations estimated that the number of people aged ≥65 years globally was 727 million. The number of older people is expected to cross 1.5 billion by 2050.[1] In 2021, the population of people aged ≥65 years was approximately 8.53 million in Korea, accounting for approximately 16.5% of the total population. This proportion is expected to continue increasing and is projected to reach approximately 20.3% of the total population by 2025, making Korea a super-aged society.[2]
As the number of older adults continues to increase, there is a high likelihood that the incidence of preventable chronic diseases such as cardiovascular diseases, hypertension (HTN), diabetes mellitus, chronic obstructive pulmonary disease, and cancer will also increase dramatically.[3,4] This trend could lead to the long-term use of multiple medications, that is, polypharmacy, to manage these chronic conditions. It has been reported that 40% of people aged ≥65 years consume 5 to 9 medications, while 18% of them consume ≥10 medications.[5] Polypharmacy can contribute to drug-related problems, such as poor medication compliance, adverse drug reactions, and drug–drug interactions, due to altered physiological functions in older adults.[6] One of the simple strategies for reducing drug-related problems is to avoid potentially inappropriate medications (PIMs) through interventions based on reliable guidelines. PIMs are defined as medications that should be avoided in older adults because this is a high-risk group and safer alternatives are available.[6]
The American Geriatrics Society (AGS) beers criteria are among the most commonly used reference sources to prevent prescription of PIMs to patients aged ≥65 years. The Beers criteria, a set of explicit criteria, were first published in 1991. After multiple revisions in 1997, 2003, 2012, and 2015, the latest version was released in 2019.[7,8] Korea has also utilized the Beers criteria to establish its own standards, which were announced by the Ministry of Food and Drug Safety (MFDS). Furthermore, the Health Insurance Review and Assessment (HIRA) introduced the drug utilization review (DUR) system to manage drugs that require cautious use in older adults. However, the warnings sent by the DUR system are frequently ignored when it is determined that the medication is necessary for patients.[9] The effectiveness of the current system is reportedly limited in improving the overall prescription safety for older adults.[10]
Therefore, this study aimed to present the policy implications for medication management by examining the outpatient prescription status by year (2015–2021) for drugs that require cautious use in older adults among the reimbursed drugs in the Korean National Health Insurance Service (NHIS).
2. Methods
2.1. Setting and sample
This study used data from the HIRA database, which contains treatment and prescription information covered by medical insurance in Korea. This study focused on outpatients aged ≥65 years, who were prescribed at least 1 PIM according to the Korean Standard Classification of Diseases (KCD) codes, a revised version of the International Classification of Diseases codes. This study combined 7 yearly datasets from 2015 to 2021 to analyze basic patient information, treatment details, and prescription details. To ensure the quality and accuracy of the data, the study excluded age and sex outliers, individuals who qualified for dual health insurance coverage, and duplicate claims. Additionally, claims from inpatients, pharmacies, and Oriental medicine were excluded from the study. This study investigated the prevalence of PIMs use and its associated factors among the older outpatients in Korea. Compulsory medical insurance in Korea, which covers approximately 98% of the population, provides a unique opportunity to study the patterns of medication use among the older adults.
2.2. Selection of PIMs
In this study, a PIMs list was created based on the ingredients recommended as elderly-focused medications in the Information Booklet for Appropriate Use of Medications in the Elderly published by the Korea Food and Drug Administration in 2015 and in the DUR system. The PIMs included in the aforementioned information booklet were based on international standards, such as the Beers Criteria in the United States, McLeod List in Canada, and STOPP/START in Ireland, and it included domestically approved ingredients.[11] The DUR system provides information to doctors and pharmacists on contraindicated medications, those contraindicated in pregnant women and children, and those requiring cautious use in older adults.[12] Since 2015, it has been checking the appropriateness of medication use in older adults, including those requiring cautious use in older adults. In July 2021, it supplemented this by announcing 102 ingredients as elderly-focused medications.[12,13]
The PIMs analyzed in this study were defined as medications excluding ingredients that are checked before prescribing and dispensing in the DUR system based on the ingredient names included in the Information Booklet for Appropriate Use of Medications in the Elderly and ingredients that cannot be assessed by the NHIS. In Korea, health insurance claims data are processed using codes for active pharmaceutical ingredients (APIs), rather than ingredient names. Therefore, the 141 selected PIMs were matched based on the List of National Health Insurance-Covered Drugs and their Reimbursement Limits. Figure 1 shows the PIMs selected for this study (see Table, Supplemental Digital Content 1, http://links.lww.com/MD/J539, which illustrates detailed final selection of PIMs).
Figure 1.
Flow chart of selection of potentially inappropriate medications for this study.
2.3. Data collection and measures
The variables used in the study included age, sex, type of health insurance, chronic diseases, number of patients, number of medical invoices, and number of prescribed medications.[14–18] Patient age was set as a categorical variable at 5-year intervals (65–69 years, 70–74 years, 75–80 years, and >80 years). Health insurance includes health insurance and medical aid, with medical aid provided to low-income or medically vulnerable populations. Chronic diseases were defined by referring to the National Health Insurance Statistical Yearbook published annually by HIRA and NHIS.[19] Specifically, chronic diseases included HTN, diabetes mellitus, cardiovascular diseases, cerebrovascular diseases, neoplasm, liver diseases, mental and behavioral disorders, respiratory tuberculosis, nervous diseases, thyroid gland diseases, chronic renal diseases, and arthropathy. Older patients who received PIMs were categorized as “yes” if they were admitted to a hospital or received outpatient treatment for the main or secondary diagnosis in that year and as “no” if they did not. The main diagnosis in the medical invoice refers to the disease primarily treated by the medical institution, whereas the secondary diagnosis is indicated as a subdiagnosis. The international classification of diseases-10 codes were modified to the KCD-10 codes for use in Korea (see Table, Supplemental Digital Content 2, http://links.lww.com/MD/J540, which illustrates KCD-10 codes for chronic diseases). The prescription status of PIMs was determined using the total number of medical invoices, number of ingredients, and average number of ingredients prescribed per person.
2.4. Statistical analysis
All statistical analyses were performed using SAS Enterprise Guide, version 7.15. A multiple logistic regression analysis was conducted to examine the associations between variables and the prescription of PIMs. In this analysis, the aggregated claim data for the entire study period were utilized. The study was approved by the Institutional Review Board of the NHIS (IRB No.2022-076-001); the health insurance claims data used in the study were anonymized and did not contain any identifiable personal information of the patients. Therefore, the data collection and analyses were conducted without ethical issues in this study.
3. Results
3.1. Trend of PIMs use
Table 1 shows the number of older outpatients who were prescribed PIMs and the number of health insurance claim statements including those for PIMs from 2015 to 2021. In 2015, the number of patients prescribed PIMs was 5145,405 and that of claim statements was 54,940,535. The proportion of older adults prescribed PIMs from the total older population of Korea showed a decreasing trend from 78.6% in 2015 to 70.3% in 2021. However, over 70% of older patients consumed 1 or more PIMs during the study period. Moreover, the proportion of claim statements, including those for PIMs, from all the claim statements for older patients showed a decreasing trend from 39.7% in 2015 to 32.8% in 2021. However, over 30% of all claims statements for older patients included 1 or more PIMs during the study period.
Table 1.
Trends of PIMs utilization by yr.
| Categories | 2015 | 2016 | 2017 | 2018 | 2019 | 2020 | 2021 |
|---|---|---|---|---|---|---|---|
| Number of patients with PIMs* | 5145,405 | 5233,003 | 5418,941 | 5590,214 | 5847,229 | 5809,141 | 6070,339 |
| (78.6%) | (77.4%) | (76.2%) | (75.3%) | (75.0%) | (71.0%) | (70.3%) | |
| Number of claims with PIMs* | 54,940,535 | 53,435,500 | 52,659,225 | 52,661,711 | 54,311,248 | 50,967,107 | 51,592,664 |
| (39.7%) | (37.3%) | (35.6%) | (34.1%) | (33.8%) | (32.9%) | (32.8%) |
PIMs = potentially inappropriate medications.
indicates that duplicated cases were removed.
3.2. Characteristics of the older patients consuming PIMs
Table 2 shows the general characteristics of the older patients who were prescribed PIMs in outpatient settings. The proportion of the older patients consuming PIMs during the study period was the highest in the 65 to 69 years age group, accounting for approximately 30% of the study sample. Particularly, patients aged ≥ 80 years who were prescribed PIMs showed an increasing trend from 20.4% in 2015 to 25.2% in 2021. Females were more likely than males to be prescribed PIMs, and >90% of the patients had health insurance. Patients without any accompanying diseases, except for HTN, commonly received PIMs; patients with HTN were more likely to receive PIMs than those without HTN were.
Table 2.
Characteristics of elderly patients prescribed with PIMs by yr.
| Variables | Categories | Yr | |||||||
|---|---|---|---|---|---|---|---|---|---|
| 2015 | 2016 | 2017 | 2018 | 2019 | 2020 | 2021 | |||
| Age | 65–69 | 1595,831 | 1607,978 | 1654,009 | 1677,171 | 1763,197 | 1784,677 | 1934,918 | |
| (31.0%) | (30.7%) | (30.5%) | (30.0%) | (30.2%) | (30.7%) | (31.9%) | |||
| 70–74 | 1389,086 | 1354,209 | 1333,512 | 1379,630 | 1439,844 | 1422,082 | 1449,033 | ||
| (27.0%) | (25.9%) | (24.6%) | (24.7%) | (24.6%) | (24.5%) | (23.9%) | |||
| 75–79 | 1109,743 | 1148,460 | 1231,612 | 1246,181 | 1245,966 | 1174,264 | 1157,510 | ||
| (21.6%) | (21.9%) | (22.7%) | (22.3%) | (21.3%) | (20.2%) | (19.1%) | |||
| ≧80 | 1050,745 | 1122,356 | 1199,808 | 1287,232 | 1398,222 | 1428,118 | 1528,878 | ||
| (20.4%) | (21.4%) | (22.1%) | (23.0%) | (23.9%) | (24.6%) | (25.2%) | |||
| Gender | Male | 2111,515 | 2158,789 | 2258,381 | 2348,989 | 2478,123 | 2490,193 | 2613,183 | |
| (41.0%) | (41.3%) | (41.7%) | (42.0%) | (42.4%) | (42.9%) | (43.0%) | |||
| Female | 3033,890 | 3074,214 | 3160,560 | 3241,225 | 3369,106 | 3318,948 | 3457,156 | ||
| (59.0%) | (58.7%) | (58.3%) | (58.0%) | (57.6%) | (57.1%) | (57.0%) | |||
| Type of | Health insurance | 4780,020 | 4843,564 | 5029,302 | 5192,903 | 5437,728 | 5396,944 | 5634,285 | |
| (92.9%) | (92.6%) | (92.8%) | (92.9%) | (93.0%) | (92.9%) | (92.8%) | |||
| Insurance | Medical aid | 365,385 | 389,439 | 389,639 | 397,311 | 409,501 | 412,197 | 436,054 | |
| (7.1%) | (7.4%) | (7.2%) | (7.1%) | (7.0%) | (7.1%) | (7.2%) | |||
| Chronic | Hypertension | No | 2274,377 | 2314,757 | 2433,747 | 2515,299 | 2644,091 | 2634,911 | 2754,765 |
| (44.2%) | (44.2%) | (44.9%) | (45.0%) | (45.2%) | (45.4%) | (45.4%) | |||
| Yes | 2871,028 | 2918,246 | 2985,194 | 3074,915 | 3203,138 | 3174,230 | 3315,574 | ||
| (55.8%) | (55.8%) | (55.1%) | (55.0%) | (54.8%) | (54.6%) | (54.6%) | |||
| Disease | Diabetes | No | 3854,047 | 3890,775 | 4010,578 | 4106,390 | 4263,417 | 4212,550 | 4358,144 |
| (74.9%) | (74.4%) | (74.0%) | (73.5%) | (72.9%) | (72.5) | (71.8%) | |||
| Mellitus | Yes | 1291,358 | 1342,228 | 1408,363 | 1483,824 | 1583,812 | 1596,591 | 1712,195 | |
| (25.1%) | (25.6%) | (26.0%) | (26.5%) | (27.1%) | (27.5%) | (28.2%) | |||
| (Present)* | Heart Disease | No | 4249,122 | 4305,096 | 4452,619 | 4576,559 | 4772,433 | 4734,637 | 4923,491 |
| (82.6%) | (82.3%) | (82.2%) | (81.9%) | (81.6%) | (81.5%) | (81.1%) | |||
| Yes | 896,283 | 927,907 | 966,322 | 1013,655 | 1074,796 | 1074,504 | 1146,848 | ||
| (17.4%) | (17.7%) | (17.8%) | (18.1%) | (18.4%) | (18.5%) | (18.9%) | |||
| Cerebrovascular Disease | No | 4509,368 | 4587,202 | 4756,609 | 4896,874 | 5096,939 | 5084,454 | 5304,993 | |
| (87.6%) | (87.7%) | (87.8%) | (87.6%) | (87.2%) | (87.5%) | (87.4%) | |||
| Yes | 636,037 | 645,801 | 662,332 | 693,340 | 750,290 | 724,687 | 765,346 | ||
| (12.4%) | (12.3%) | (12.2%) | (12.4%) | (12.8%) | (12.5%) | (12.6%) | |||
| Neoplasm | No | 4711,143 | 4768,996 | 4924,070 | 5055,616 | 5270,218 | 5229,829 | 5443,175 | |
| (91.6%) | (91.1%) | (90.9%) | (90.4%) | (90.1%) | (90.0%) | (89.7%) | |||
| Yes | 434,262 | 464,007 | 494,871 | 534,598 | 577,011 | 579,312 | 627,164 | ||
| (8.4%) | (8.9%) | (9.1%) | (9.6%) | (9.9%) | (10.0%) | (10.3%) | |||
| Liver | No | 4687,464 | 4748,303 | 4910,872 | 5021,911 | 5205,712 | 5183,062 | 5387,248 | |
| (91.1%) | (90.7%) | (90.6%) | (89.8%) | (89.0%) | (89.2%) | (88.7%) | |||
| Disease | Yes | 457,941 | 484,700 | 508,069 | 568,303 | 641,517 | 626,079 | 683,091 | |
| (8.9%) | (9.3%) | (9.4%) | (10.2%) | (11.0%) | (10.8%) | (11.3%) | |||
| Mental and behavior | No | 3758,590 | 3784,522 | 3918,708 | 3996,455 | 4156,548 | 4126,872 | 4306,945 | |
| (73.0%) | (72.3%) | (72.3%) | (71.5%) | (71.1%) | (71.0%) | (71.0%) | |||
| Disorder | Yes | 1386,815 | 1448,481 | 1500,233 | 1593,759 | 1690,681 | 1682,269 | 1763,394 | |
| (27.0%) | (27.7%) | (27.7%) | (28.5%) | (28.9%) | (29.0%) | (29.0%) | |||
| Respiratory | No | 5118,323 | 5206,623 | 5394,084 | 5566,197 | 5824,406 | 5790,407 | 6052,975 | |
| (99.5%) | (99.5%) | (99.5%) | (99.6%) | (99.6%) | (99.7%) | (99.7%) | |||
| Tuberculosis | Yes | 27,082 | 26,380 | 24,857 | 24,017 | 22,823 | 18,734 | 17,364 | |
| (0.5%) | (0.5%) | (0.5%) | (0.4%) | (0.4%) | (0.3%) | (0.3%) | |||
| Nervous | No | 3809,807 | 3821,727 | 3940,905 | 4020,735 | 4155,293 | 4136,646 | 4276,384 | |
| (74.0%) | (73.0%) | (72.7%) | (71.9%) | (71.1%) | (71.2%) | (70.4%) | |||
| Disease | Yes | 1335,598 | 1411,276 | 1478,036 | 1569,479 | 1691,936 | 1672,495 | 1793,955 | |
| (26.0%) | (27.0%) | (27.3%) | (28.1%) | (28.9%) | (28.8%) | (29.6%) | |||
| Thyroid gland | No | 4875,362 | 4947,845 | 5116,194 | 5255,436 | 5480,097 | 5441,290 | 5652,519 | |
| (94.8%) | (94.6%) | (94.4%) | (94.0%) | (93.7%) | (93.7%) | (93.1%) | |||
| Disease | Yes | 270,043 | 285,158 | 302,747 | 334,778 | 367,132 | 367,851 | 417,820 | |
| (5.2%) | (5.4%) | (5.6%) | (6.0%) | (6.3%) | (6.3%) | (6.9%) | |||
| Chronic renal | No | 5056,430 | 5131,594 | 5306,374 | 5462,273 | 5700,941 | 5656,644 | 5900,829 | |
| (98.3%) | (98.1%) | (97.9%) | (97.7%) | (97.5%) | (97.4%) | (97.2%) | |||
| *Disease | Yes | 88,975 | 101,409 | 112,567 | 127,941 | 146,288 | 152,497 | 169,510 | |
| (1.7%) | (1.9%) | (2.1%) | (2.3%) | (2.5%) | (2.6%) | (2.8%) | |||
| Arthropathy | No | 2792,275 | 2807,384 | 2920,535 | 2999,014 | 3121,101 | 3218,308 | 3339,689 | |
| (54.3%) | (53.6%) | (53.9%) | (53.6%) | (53.4%) | (55.4%) | (55.0%) | |||
| Yes | 2353,130 | 2425,619 | 2498,406 | 2591,200 | 2726,128 | 2590,833 | 2730,650 | ||
| (45.7%) | (46.4%) | (46.1%) | (46.4%) | (46.6%) | (44.6%) | (45.0%) | |||
PIMs = potentially inappropriate medications.
In the case of patients who prescribed potentially inappropriate medicines for the elderly patients have 2 or more claims for the main diagnosis or subdiagnosis in the same year, then counts “Yes” (based on the health insurance claims). If there are no more than 2 claims due to inpatient or outpatient treatment due to chronic disease, it counts as 0.
** means that duplicated cases were removed.
3.3. Total patients and claims of PIMs by sex
Figures 2 and 3 show the distribution of PIMs prescribed to older patients by sex. The number of PIMs prescribed to older male patients decreased from 111 in 2015 to 100 in 2021. The number of health insurance claim statements including PIMs decreased from approximately 22.4 million in 2015 to 22 million in 2016; however, it continued to increase until 2019. Notably, in 2020, it decreased to approximately 22.5 million, whereas in 2021, it increased to approximately 22.8 million. The number of PIMs prescribed to older female patients was similar to that of older male patients, decreasing from 111 in 2015 to 100 in 2021. The number of health insurance claim statements including PIMs for older female patients decreased from approximately 32.5 million in 2015 to 28.4 million in 2020; however, it increased to approximately 28.7 million in 2021. Both male and female older patients showed a decrease in the number of PIMs prescribed per year; however, the number of health insurance claims for PIMs was higher in female patients than in male patients.
Figure 2.
Total number of claims and drugs used in male patients.
Figure 3.
Total number of claims and drugs used in female patients.
3.4. APIs of PIMs by sex
Table 3 shows the most commonly prescribed ingredients by sex based on the API code in health insurance claim statements for PIMs among older patients during the study period. In older male patients, tamsulosin was the most frequently prescribed drug, followed by eperisone, cimetidine, levosulpiride, and prednisolone in that order (see Table, Supplemental Digital Content 3, http://links.lww.com/MD/J541, which illustrates list of the top 10 PIMs prescribed to male patients). In older female patients, eperisone was the most frequently prescribed drug, followed by cimetidine, levosulpiride, alprazolam, and prednisolone in that order (see Table, Supplemental Digital Content 4, http://links.lww.com/MD/J542, which illustrates list of the top 10 PIMs prescribed to female patients). Zolpidem was more frequently prescribed for female patients (ranked 6th) than for male patients (ranked 7th).
Table 3.
Rank of PIMs prescribing claims by sex.
| Rank* | Total period of research (2015~2021) | |
|---|---|---|
| Male | Female | |
| 1 | Tamsulosin | Eperisone |
| 2 | Eperisone | Cimetidine |
| 3 | Cimetidine | Levosulpiride |
| 4 | Levosulpiride | Alprazolam |
| 5 | Prednisolone | Prednisolone |
| 6 | Alprazolam | Zolpidem |
| 7 | Zolpidem | Gabapentin |
| 8 | Terazosin | Etizolam |
| 9 | Gabapentin | Ferrous sulfate |
| 10 | Alfuzosin | Risedronate |
PIMs = potentially inappropriate medications.
indicates that duplicated cases were removed.
3.5. Trends of PIMs by sex and age
Table 4 shows the prescription trends of PIMs among the patients according to sex and age during the study period. The total number of health insurance claim statements for older patients who received prescriptions in outpatient clinics from 2015 to 2021 was approximately 1.05 billion, of which approximately 303 million included at least 1 PIM. The PIMs-related claims accounted for approximately 28.7% of the total claims.
Table 4.
Trends of PIM use in elderly Koreans by sex and age.
| Gender | Age group | Total period of research (2015~2021) | Ratio of PIMs claims (A/B) | |||||
|---|---|---|---|---|---|---|---|---|
| Number of patients* | Number of PIMs claims* (A) | Total Number of claims* (B) | ||||||
| N | % | N | % | N | % | % | ||
| Male | 65–69 | 2256,414 | 36.4 | 36,020,392 | 27.4 | 133,163,183 | 30.6 | 27.0 |
| 70–74 | 1714,330 | 27.6 | 34,419,005 | 26.2 | 117,155,209 | 26.9 | 29.4 | |
| 75–79 | 1290,179 | 20.8 | 31,416,701 | 23.9 | 98,875,387 | 22.7 | 31.8 | |
| ≥80 | 944,480 | 15.2 | 29,547,609 | 22.5 | 86,165,162 | 19.8 | 34.3 | |
| Sub total | 6205,403 | 100.0 | 131,403,707 | 100.0 | 435,358,941 | 100.0 | 100.0 | |
| Female | 65–69 | 2556,729 | 31.7 | 41,937,247 | 24.4 | 167,723,470 | 27.0 | 25.0 |
| 70–74 | 2063,915 | 25.6 | 40,675,920 | 23.7 | 154,298,971 | 24.8 | 26.4 | |
| 75–79 | 1758,390 | 21.8 | 40,978,113 | 23.8 | 144,090,174 | 23.2 | 28.4 | |
| ≥80 | 1694,649 | 21.0 | 48,308,892 | 28.1 | 155,970,725 | 25.1 | 31.0 | |
| Sub total | 8073,683 | 100.0 | 171,900,172 | 100.0 | 622,083,340 | 100.0 | 100.0 | |
| Total | 14,279,086 | - | 303,303,879 | - | 1057,442,281 | - | 28.7 | |
PIMs = potentially inappropriate medications.
indicates that duplicated cases were removed.
The total number of male patients prescribed PIMs was 6205,403. Among the female patients, the 65 to 69 years age group had the highest number of PIMs-related claims (approximately 36 million) as well as total number of claims (approximately 133 million) among all the age groups. As the age increased, the number of PIMs-related claims and total claims decreased; however, the proportion of PIMs-related claims from the total claims increased. The total number of female patients prescribed PIMs was 8073,683. Among the female patients, the number of PIMs-related claims was highest in the > 80 years age group (approximately 48.3 million), whereas the total number of claims was highest in the 65 to 69 years age group (approximately 167 million). Similar to male patients, the proportion of PIMs-related claims increased with age.
3.6. Multiple logistic regression analysis for the associations of variables with the prescription of PIMs
Table 5 presents the factors associated with the prescription of PIMs during the study period. In the multiple logistic regression analysis, age categories (70–74 years and ≥80 years), gender, type of insurance, and chronic diseases showed associations with the prescription of PIMs. Additionally, the results of the multiple logistic regression analysis differed between males and females in terms of age and chronic diseases (see Table, Supplemental Digital Content 5, http://links.lww.com/MD/J543, which illustrates multiple logistic regression analysis for the associations of variables with the prescription of PIMs by sex).
Table 5.
Multiple logistic regression analysis for the associations of variables with the prescription of PIMs.
| Variables | OR* (95% CI) | P value | |
|---|---|---|---|
| Age** | 65–69 | Ref | |
| 70–74 | 0.96 (0.94–0.99) | <.001 | |
| 75–79 | 1.00 (0.98–1.03) | .855 | |
| ≥80 | 1.04 (1.02–1.07) | <.001 | |
| Gender | Female | Ref | <.001 |
| Male | 1.27 (1.25–1.29) | ||
| Type of insurance*** | Health insurance | Ref | <.001 |
| Medical Aid | 1.71 (1.67–1.74) | ||
| Chronic disease**** | Hypertension (Yes) | 1.03 (1.01–1.05) | <.001 |
| Diabetes Mellitus (Yes) | 1.14 (1.12–1.16) | ||
| Heart disease (Yes) | 1.33 (1.31–1.69) | ||
| Cerebrovascular disease (Yes) | 1.37 (1.34–1.39) | ||
| Neoplasm (Yes) | 1.43 (1.40–1.46) | ||
| Liver disease (Yes) | 1.11 (1.09–1.13) | ||
| Mental and behavior disorder (Yes) | 5.59 (5.82–6.16) | ||
| Respiratory Tuberculosis (Yes) | 1.10 (1.04–1.17) | ||
| Nervous Disease (Yes) | 2.63 (2.57–2.70) | ||
| Thyroid gland Disease (Yes) | 1.09 (1.07–1.11) | ||
| Chronic Renal Disease (Yes) | 1.16 (1.13–1.10) | ||
| Arthropathy (Yes) | 0.92 (0.90–0.94) | ||
The dependent variable was divided into 2 groups: ≥5 PIMs vs <5 PIMs in 1 claim.
As the patients’ age increased during the study period, it was defined as the age at which the last claim data was processed.
The type of insurance was classified as medical aid if patients received medical aid at least once.
*Patients who had been diagnosed with a chronic disease at least once were categorized as those with chronic diseases
PIMs = potentially inappropriate medications.
4. Discussion
This study analyzed the annual prescription status of PIMs among the older patients receiving outpatient care in Korea and investigated the differences in prescription patterns by sex and age. Although the number of patients who received PIMs decreased only in 2020, the total number of patients receiving PIMs increased throughout the study period. The number of claim statements gradually decreased compared to that in 2015, though it increased in 2021 when compared to that in 2020. Most patients who received PIMs were 65 to 69 years old, female, had national health insurance, and had chronic HTN. The number of PIM ingredients consumed decreased in both males and females throughout the study period. Among the APIs, tamsulosin and eperisone were the most frequently prescribed PIMs for male and female patients, respectively. In terms of prescription patterns according to sex, the number of PIM ingredients and claim statements decreased with age; however, the average number of PIM ingredients per patient increased with age in the male patients. As female patients aged, the number of patients and average number of PIM ingredients per patient decreased; however, the number of claim statements increased from age ≥75 years.
The number of patients and claims for PIMs prescribed in Korea increased continuously during the study period (2015–2021), which is similar to the findings of studies by Lee et al (2019) and Cho et al (2019).[20,21] Other studies have performed trend analyses of short-term (1 year) studies or of specific components of PIMs, such as anti-depressants, benzodiazepines, or opioids.[22,23] However, this study is relevant, because it integrates drugs excluded from the AGS Beers criteria and Korea DUR system and comprehensively analyzes the overall trend of PIMs prescription in Korea by year. However, since this study retrospectively analyzed the prescription results of the PIMs components from 2015 to 2020 based on the 2021 criteria, the results should be interpreted cautiously.
The prescription status of PIMs by sex in older patients in Korea has shown a decrease in the number of prescribed components for both male and female patients. This is similar to the findings of Thorell et al (2020), who reported a decrease in the number of prescribed components for both sexes.[24] However, male patients showed an increasing trend in the number of prescription claims compared to female patients, indicating the need for caution when prescribing for older male patients in Korea. Additionally, throughout the study period, the total number of patients, number of prescription claims, and average number of drugs consumed by patients were much higher among female patients than among male patients. This highlights the need to manage medical use and prescription for older female patients in Korea, as they have a longer life expectancy and higher medical utilization as compared to males.[25] Moreover, the reported increase in the number of prescribed drugs and daily dosing frequency among older patients in Korea can affect medication compliance,[26–28] further emphasizing the need for management of such prescriptions.
In 2020, the number of prescription records of PIMs for older patients decreased dramatically, and this could be attributed to the decrease in the use of health insurance in Korea due to the coronavirus disease (COVID-19) pandemic worldwide. The HIRA and NHIS (2021) report and Oh et al (2021) study also indicated that the number of health insurance claims in Korea decreased in 2020 when compared to that before the COVID-19 pandemic,[19,29] suggesting results similar to those of previous studies. In 2021, along with the increase in the use of medical services in Korea owing to various factors, such as the decrease in the number of COVID-19 cases and normalization of the medical system, the number of claims for PIMs also increased. It is expected that after 2022, as the COVID-19 pandemic subsides and daily life is restored, the basic use of medical services will increase, and simultaneously, the prescription of PIMs is expected to increase, indicating the need for management of prescription.
During the study period, tamsulosin was the most commonly prescribed PIMs component for older male patients in Korea (ranked 1st), which is the main ingredient used to treat benign prostatic hyperplasia. Moreover, terazosin (ranked 8th) and alfuzosin (ranked 10th) were included in the top 10 PIMs prescribed to older male patients in Korea as alpha-blockers, similar to tamsulosin. Alpha-blockers are reportedly associated with orthostatic hypotension, and risk of falls has been reported in older male patients with benign prostatic hyperplasia due to alpha-blockers, including tamsulosin.[30–32] Therefore, prescription management of alpha-blockers, including tamsulosin, is warranted in Korea.
In contrast, among older female patients, eperisone was the most commonly prescribed PIM (ranked 1st). Eperisone is used to alleviate pain, such as low back pain[33]; it is a common PIM used for both male and female patients, with eperisone being the second most prescribed PIM in male patients. However, compared to male patients, female patients had more number of prescriptions for alprazolam (ranked 4th), zolpidem (ranked 6th), and etizolam (ranked 8th). Alprazolam and etizolam are benzodiazepine drugs acting as hypnotic and anxiolytic agents and are frequently used to treat anxiety and insomnia in older adults. However, these drugs are reported to have a risk of dependence, falls, and fractures in older patients.[34–36] Zolpidem is a non-benzodiazepine drug that is useful in treating insomnia; however, it is reportedly associated with a risk of fractures in older patients.[37,38] Recent studies have also reported that zolpidem consumption is a risk factor for suicide attempts in older Korean adults.[39] Therefore, close attention should be paid to the management of these drugs in older patients, regardless of sex, as alprazolam (ranked 6th) and zolpidem (ranked 7th) were also prescribed to male Korean patients throughout the study period.
Finally, in Korea, PIMs are reported and managed based on the Korean criteria for PIMs, which are based on the AGS Beers criteria, by the MFDS and Korea Institute of Drug Safety and Risk Management. Moreover, PIMs are also managed in Korea through the DUR system. However, MFDS and Korea institute of drug safety and risk management report on the drug ingredients of the PIMs, and the DUR is not a mandatory system for drug management in Korea; hence, there are blind spots in the drug management protocols. Therefore, national management through legal revisions and establishment of regulations are necessary.
The strength of this study is that it provides information on the status of medications prescribed to the entire older adult population of 1 country. Previous studies using Korean data analyzed the patient sample data targeting approximately 1.5 million people; however, our study used the entire claims data instead of sample data. Secondly, the analysis was performed using the PIMs ingredients for all reimbursable medications during the study period in Korea, rather than evaluating specific PIMs (e.g., benzodiazepines), a limited number of PIMs in the DUR system, or PIMs prescribed during a single year or in a single medical institution. Lim et al analyzed PIMs prescribed to elderly patients during a 1-year period in a tertiary hospital,[40] and Kim et al evaluated PIMs prescribed in an emergency department.[41] However, this study presents the complete prescribing trends of PIMs reimbursed in Korea over a span of 7 consecutive years. Finally, the usability of the results is another strength of this study. Our study can be used as policy data for medication for older adults and as basic data for comparison with other countries.
However, our study has some limitations. First, it was difficult to identify individual patient characteristics and influencing factors owing to the limitations of the claims data. Since the claims data are reimbursement data for prescriptions, identifying individual patient characteristics is difficult. Second, caution should be exercised regarding the APIs presented in this study. Our study was based on the Beers criteria, and we constructed the analyzed ingredients by including all the DUR criteria. However, there may be ingredients that require less caution than those that are actually needed in clinical practice; therefore, there may be an overestimation of the PIMs prescriptions for the older adults, and appropriate caution should be exercised. Lastly, almost all of the PIMs that can be prescribed and claimed under Korean health insurance were included in the analysis to minimize bias in their selection. However, certain PIMs managed by the DUR system were excluded to ensure the construction of an appropriate analysis dataset.
5. Conclusion
This study aimed to identify the prescription patterns of PIMs among older outpatients in Korea, according to sex and year, from 2015 to 2021. This study used 141 criteria based on the Beers criteria and data from the Korean NHIS claims database. The results showed that although the number of patients who were prescribed PIMs increased over the study period, the number of claims decreased when compared to that in 2015. Particularly, the number of claims decreased in 2020 due to COVID-19 but increased again in 2021. Tamsulosin and eperisone were the most commonly prescribed PIMs for male and female patients, respectively. However, female patients were prescribed more benzodiazepines and zolpidem than the male patients were, suggesting the need for overall management. These results provide valuable information on the national status of PIMs and can be used for comparisons with other countries. Therefore, this study contributes to the establishment of policies for medication prescription and management.
Acknowledgment
This work was supported by a National Research Foundation of Korea (NRF) grant, funded by the Ministry of Science and ICT (NRF-2022R1F1A1070333), Korea.
Author contributions
Conceptualization: Jae-Yong Dong, Young-Mo Yang.
Data curation: Jae-Yong Dong.
Formal analysis: Jae-Yong Dong.
Investigation: Jae-Yong Dong, Jin-Han Ju, Young-Mo Yang.
Methodology: Jae-Yong Dong, Young-Mo Yang.
Supervision: Young-Mo Yang.
Validation: Young-Mo Yang.
Writing – original draft: Jae-Yong Dong, Jin-Han Ju.
Writing – review & editing: Young-Mo Yang.
Supplementary Material
Abbreviations:
- AGS
- American Geriatrics Society
- APIs
- active pharmaceutical ingredients
- COVID-19
- coronavirus disease
- DUR
- drug utilization review
- HIRA
- health insurance review and assessment
- HTN
- hypertension
- KCD
- Korean standard classification of diseases
- MFDS
- ministry of food and drug safety
- NHIS
- National Health Insurance Service
- PIMs
- potentially inappropriate medications
Supplemental Digital Content is available for this article.
The authors have no conflicts of interest to disclose.
The data that support the findings of this study are available from a third party, but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available.
How to cite this article: Dong J-Y, Ju J-H, Yang Y-M. Analysis of the prescription trends of potentially inappropriate medications in Korean older outpatients by sex: A retrospective study using data from the health insurance review and assessment service. Medicine 2023;102:34(e34818).
Contributor Information
Jae-Yong Dong, Email: jaeyong@hira.or.kr.
Jin-Han Ju, Email: allegro90@hira.or.kr.
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