Introduction
Multiple morbidity in older patients contributes to an increased use of medications, which increases the risk of interactions both between medications and between medications and diseases. This makes the treatment of older patients more complicated and the effects of medication treatments more difficult to predict and evaluate [
1,
2]. Furthermore, the changes in pharmacokinetic and pharmacodynamic functions that follow with ageing, for example impaired renal function, increase the risk of adverse drug effects [
3]. Some of the medications used among older patients are known to be potentially inappropriate medications (PIMs), defined as medications for which the risks outweigh the benefits [
4]. The use of PIMs among older patients is a worldwide problem, and many studies have found a high prevalence of PIMs. For example, a register-based study from Sweden where a prevalence of 19% was found when the Swedish quality indicators were applied. In this study, patients 65 years and older in nursing homes and in hospital were included [
5]. Another study found that according to the European Union (EU) (7)-PIM list, 41% in-hospital patients had one or more PIM prescribed [
6]. Outside Sweden, one study using Beers criteria found a prevalence of 58% among older in-hospital patients in Italy, and another study performed among old patients discharged from a hospital in Croatia found PIMs in 184 of 267 patients (67%) when the EU (7)-PIM list was applied [
4,
7]. The use of PIMs has been associated with negative outcomes, for example, increased risk of hospitalisation [
8,
9].
To be able to describe drug use in terms of quality, and to be able to assess and correct older patients’ medication regimens, tools or criteria to evaluate the appropriateness of prescriptions have been developed [
10]. Criteria can be classified as implicit or explicit criteria. Implicit criteria (or patient-specific criteria) rely on expert professional judgement and focus on the patient, addressing the entire medication regimen. Explicit criteria on the other hand can be applied with little or no clinical judgement, and the criteria are not patient-specific, i.e. the medications are considered inappropriate regardless of the effects on the individual patient [
11]. Explicit criteria might be country specific and might need to be adjusted to country-specific therapeutic traditions [
12]. Among of the most commonly used and studied explicit criteria are Beer’s criteria, developed in the US for the evaluation of PIMs among older patients [
13‐
16]. Beside these criteria, several other explicit criteria have been developed in different countries [
12]. In Sweden, indicators for evaluating the quality of older patients’ drug therapies were first published in 2004 and updated in 2010 and 2017 [
17,
18]. Recently, a European list of PIMs has been developed, the EU (7)-PIM list [
19]. The different tools to assess PIMs seem however to have a large variety in methodological aspects and in clinical validation, and prevalence of PIM has significantly varied when different criteria have been applied [
12,
20]. This raises questions about the appropriateness, validity and how feasible the different tools are in use. Since both the Swedish quality indicators and the (EU) (7)-PIM list have been developed for use in Sweden/Europe, a comparison between prevalence and type of PIMs using the two tools is warranted. As far as we know, this has so far not been done.
Results
Of 103 patients included in the main study, 10 patients < 65 years were excluded in this specific study, leaving 93 patients’ data to be analysed. The age was 79.5 ± 8.2 years (mean ± SD), and 51 (54.8%) were women. The number of regularly prescribed medications at admission was 8.2 ± 3.6 (mean ± SD). Furthermore, 46 (49.5%) patients had hypertension and 26 (28.0%) patients had arrhythmias (Table
1).
Table 1
Characteristics of the study population
Age (years), mean ± SD | 79.5 ± 8.2 |
Women, n (%) | 51 (54.8) |
Number of regularly prescribed medications at admission, mean ± SD | 8.2 ± 3.6 |
Diseases |
Arrhythmias, n (%) | 26 (28.0) |
Cancer, n (%) | 21 (22.6) |
Chronic respiratory disease, n (%) | 15 (16.1) |
Diabetes mellitus, n (%) | 17 (18.3) |
Hypertension, n (%) | 46 (49.5) |
Heart failure, n (%) | 22 (23.7) |
Stroke/TIA, n (%) | 10 (10.8) |
According to the Swedish quality indicators, 17 (18.3%) patients in the study sample had one PIM. No patient had more than one PIM prescribed concomitantly. The most commonly represented PIM class among the identified prescriptions according to the Swedish quality indicators (n = 17) was NSAIDs [n = 5 (29.4%)] (Table
2). The most commonly involved PIMs were diclofenac [n = 4 (23.5%)] and tramadol [n = 3 (17.6%)].
Table 2
Prescribing frequency for each identified PIM according to the Swedish quality indicators and the EU (7)-PIM list
A03F | Medications for functional gastrointestinal disorder—propulsives | n/a | 1 (1.6%) |
| Metoclopramide (A03FA01) | n/a | 1 (1.6%) |
A06A | Laxatives | n/a | 3 (4.7%) |
| Sodium picosulfate (A06AB08) | n/a | 3 (4.7%) |
A 10 | Blood glucose lowering medications, excl. insulins | n/a | 2 (3.1%) |
| Glibenclamide (A10BB01) | 1 (5.9%) | 1 (1.6%) |
| Glipizide (A10BB07) | n/a | 1 (1.6%) |
B01A | Antithrombotic agents | n/a | 11 (17.2%) |
| Rivaroxaban (B01AF01) | n/a | 1 (1.6%) |
| Apixaban (B01AF02) | n/a | 10 (15.6%) |
C01 | Cardiac therapy | n/a | 8 (12.5%) |
| Digoxin (C01AA05) | n/a | 4 (6.3%) |
| Amiodarone (C01BD01) | n/a | 4 (6.3%) |
C02 | Antihypertensive therapy | n/a | 1 (1.6%) |
| Doxazosin (C02CA04) | n/a | 1 (1.6%) |
C03D | Diuretics, potassium-sparing agents | n/a | 5 (7.8%) |
| Spironolactone (> 25 mg/days) | n/a | 5 (7.8%) |
C07 | Betablocking agents | n/a | 1 (1.6%) |
| Sotalol (C07AA07) | n/a | 1 (1.6%) |
C08 | Calcium channel blockers | n/a | 1 (1.6%) |
| Diltiazem (C08DB01) | n/a | 1 (1.6%) |
G03C | Oestrogens (oral) | n/a | 2 (3.1%) |
| Estradiol (G03CA03) | n/a | 1 (1.6%) |
| Estriol (G03CA04) | n/a | 1 (1.6%) |
G04 | Other urologicals, incl. antispasmodic medications | n/a | 2 (3.1%) |
| Tolterodine (G04BD07)a | 1 (5.9%) | 1 (1.6%) |
| Solifenacin (G04BD08)a | 1 (5.9%) | 1 (1.6%) |
M01A | NSAID | 5 (29.4%) | 4 (6.3%) |
| Diclofenac (M01AB05) | 4 (23.5%) | 4 (6.3%) |
| Naproxen (M01AE02) | 1 (5.9%) | n/a |
N02 | Analgesics—opioids | n/a | 3 (4.7%) |
| Codeine (N02AJ06) | 1 (5.9%) | n/a |
| Tramadol (N02AX02) | 3 (17.6%) | 3 (4.7%) |
N03A | Antiepileptics | n/a | 1 (1.6%) |
| Carbamazepine (N03AF01) | n/a | 1 (1.6%) |
N04 | Antiparkinson medications | n/a | 2 (3.1%) |
| Pramipexole (N04BC05) | n/a | 2 (3.1%) |
N05A | Antipsychotics | 1 (5.9%) | 1 (1.6%) |
| Flupentixol (N05AF01) | 1 (5.9%) | 1 (1.6%) |
N05B | Anxiolytic medications | n/a | 2 (3.1%) |
| Hydroxyzine (N05BB01)a | 1 (5.9%) | 1 (1.6%) |
| Diazepam (N05BA01) | 1 (5.9%) | 1 (1.6%) |
N05C | Hypnotics and sedatives | n/a | 12 (18.8%) |
| Zopiclone (N05CF01) > 3.75 mg/days | n/a | 9 (14.1%) |
| Zolpidem (N05CF02) > 5 mg/days | n/a | 1 (1.6%) |
| Clomethiazole (N05CM02) | n/a | 1 (1.6%) |
| Propiomazine (N05CM06) | 1 (5.9%) | 1 (1.6%) |
N06A | Antidepressants | n/a | 2 (3.1%) |
| Amitriptyline (N06AA09)a | 1 (5.9%) | 1 (1.6%) |
| Venlafaxine (N06AX16) | n/a | 1 (1.6%) |
According to the EU (7)-PIMs list, 42 (45.2%) patients had one or more PIMs, of whom 25 (26.9%) had one PIM, 13 (14.0%) had two PIMs, 3 (3.2%) had three PIMs, and 1 (1.1%) had four PIMs. The three most commonly represented PIM classes among the identified prescriptions (n = 64) were hypnotics and sedatives [n = 12 (18.8%)], antithrombotic agents [n = 11 (17.2%)], and cardiac therapy [n = 8 (12.5%)]. The most commonly involved PIMs were apixaban [n = 10 (15.6%)] and zopiclone [n = 9 (14.1%)] (Table
2).
No significant associations between having a PIM according to the Swedish quality indicators and diseases, sex, age, or number of medications at admission were found in the regression analysis (Table
3).
Table 3
Comparison between patients with and without PIMs using the Swedish quality indicators as the identification tool
Cases, n | 17 | 76 | |
Sex, n (%) |
Female | 10 (58.8) | 41 (53.9) | 1.22 (0.42–3.54) |
Age (years), mean ± SD | 78.3 ± 8.2 | 79.7 ± 8.3 | 0.94 (0.92–1.05) |
Number of medications at admission, mean ± SD | 9.7 ± 2.6 | 7.8 ± 3.7 | 1.16 (1.00–1.35) |
Diseases |
Arrhythmias, n (%) | 2 (11.8) | 24 (31.6) | 0.30 (0.06–1.37) |
Cancer, n (%) | 3 (17.6) | 18 (23.7) | 0.69 (0.18–2.68) |
Chronic respiratory disease, n (%) | 5 (29.4) | 10 (13.2) | 2.75 (0.80–9.48) |
Diabetes mellitus, n (%) | 6 (35.3) | 11 (14.5) | 3.22 (0.99–10.50) |
Hypertension, n (%) | 12 (70.6) | 34 (44.7) | 2.97 (0.95–9.24) |
Heart failure, n (%) | 4 (23.5) | 18 (23.7) | 0.99 (0.29–3.42) |
Stroke/TIA, n (%) | 2 (11.8) | 8 (10.5) | 1.13 (0.22–5.89) |
No significant associations between age, sex, diseases, number of medications at admission, and having PIMs according to the EU (7)-PIM list were found (Table
4).
Table 4
Comparison between patients with and without PIMs using the EU (7)-PIM list as the identification tool
Cases, n | 42 | 51 | |
Sex, n (%) |
Female, n (%) | 22 (52.4) | 29 (56.9) | 0.83 (0.37–1.90) |
Age (years), mean ± SD | 80.3 ± 7.8 | 78.8 ± 8.6 | 1.02 (0.97–1.08) |
Number of medication at admission, mean ± SD | 8.2 ± 3.1 | 8.2 ± 3.9 | 1.00 (0.89–1.13) |
Diagnosis |
Arrhythmias, n (%) | 14 (33.3) | 12 (23.5) | 1.63 (0.65–4.04) |
Cancer, n (%) | 10 (23.8) | 11 (21.6) | 1.14 (0.43–3.01) |
Chronic respiratory disease, n (%) | 9 (21.4) | 6 (11.8) | 2.05 (0.66–6.31) |
Diabetes mellitus, n (%) | 7 (16.7) | 10 (19.6) | 0.82 (0.80–2.38) |
Hypertension, n (%) | 21 (50.0) | 25 (49.0) | 1.04 (0.46–2.35) |
Heart failure, n (%) | 10 (23.8) | 12 (23.5) | 1.02 (0.39–2.65) |
Stroke/TIA, n (%) | 3 (7.1) | 7 (13.7) | 0.48 (0.12–2.00) |
Discussion
The main finding of this study was that 18% of the study population was taking one PIM according to the Swedish quality indicators, and 45% were taking one or more according to the EU (7)-PIM list. Furthermore, according to the Swedish quality indicators, the most common PIMs were diclofenac and tramadol, while according to the EU (7)-PIM list the most common PIMs were apixaban and zopiclone.
The prevalence of PIMs according to the Swedish quality indicators (18%) is very similar to a previous register study in Sweden (19%) where the same tool was applied, although not exactly the same indicators [
5]. When applying the Swedish quality indicators, the most frequently occurring PIMs in the present study were diclofenac, tramadol, and anticholinergic medications. The use of tramadol in older patients increases the risk for nausea, fatigue, dizziness, and confusion and therefore should be prescribed carefully to this patient group [
18]. Further, the use of NSAIDs is associated with risks of gastrointestinal bleeding, acute renal failure, and impaired heart failure [
22,
23]. Anticholinergic medications such as hydroxyzine increase the risk of constipation and urinary retention as well as confusion and should be used with caution [
24]. Notably, the use of tramadol, NSAIDs, and anticholinergic medications decreased between 2007 and 2013, perhaps at least partly due to medication reviews performed in the county of Västerbotten [
25]. The prevalence of PIMs among older patients according to the EU (7)-PIM list is also in line with previous studies using the same identification tool, a prevalence between 41% and 67% has been reported [
6,
7,
26‐
28]. According to the EU (7)-PIM list, apixaban was the most commonly prescribed PIM in the present study. Current recommendations published in Sweden in 2017 state that apixaban is recommended as one of the first-line treatment choices for arrhythmias [
29]. The recommendation states that apixaban causes fewer haemorrhagic strokes, fewer severe bleedings, and a lower mortality compared to warfarin. Nevertheless, there is limited experience regarding the use of apixaban in older patients, and the drug presents an increased risk of bleeding events. It is therefore important to continuously evaluate the use of the drug and adjust the dosage if necessary [
29]. Further, zopiclone at doses > 3.75 mg was the second most common PIM according to the EU (7)-PIM list. In Sweden, zopiclone is the first-line sedative recommendation for older patients in Sweden, with a maximum daily dose of 7.5 mg among this population (although 5 mg often is considered enough) [
18]. Still, falls and impaired cognitive function are possible adverse drug reactions to zopiclone, which is why it should be used with caution [
18].
In order to improve the use of medication among older patients and to minimize adverse drug effects, the medications prescribed to this patient population must be continuously evaluated. Tools and criteria might therefore be used to assess the appropriateness of a medication, and it is important that these tools and criteria are reliable when it comes to detecting PIMs. Consequently, it is of interest to compare the prevalence obtained by using different tools. When considering the different results in this study using the two different tools, it is important to note the heterogeneity in the lists of medications between the tools. The EU (7)-PIM list is deemed to be a sensitive tool, which might explain the high prevalence of PIMs when the suggested criteria are applied [
19]. In the present study, 68 substances were classified as PIMs according to the Swedish quality indicators (including NSAIDs and antipsychotics), while 137 substances were classified as such according to the EU (7)-PIM list. Furthermore, the EU(7)-PIM list recommends lower maximum doses in some cases compared to current Swedish guidelines [
18]. To some extent, the higher prevalence of PIMs when using the EU (7)-PIM list is due to the fact that some medications on that list, such as zopiclone and apixaban, are recommended as first-line treatments according to the Swedish guidelines as discussed above. If apixaban and zopiclone were to be excluded, the prevalence of PIMs would decrease from 45 to 25% according to the EU (7)-PIM list. In accordance to the results of the present study, two previous studies comparing EU (7)-PIM and national PIM criteria found that the prevalence of PIMs according to EU (7)-PIM were higher than according to the national lists [
7,
27]. Altogether, this raises the question about the pertinence of explicit criteria. Identifying PIMs are important in order to reduce drug-related problems among old patients, but of course, in some patients, prescription of these medications might have been medically well motivated and valid. In practice, these criteria should always be the used in consideration with an individual medical judgment.
There were no significant associations in the simple analysis between sex, age, higher number of medications, or different diseases and having PIMs according to the Swedish quality indicators. This is in contrast with the findings of a nationwide, cross-sectional, register-based study using the criteria from the Swedish quality indicators, where significant associations between women, age, and a higher number of medications and having PIMs were found [
5]. Further, no significant associations with the factors mentioned above and PIMs in the simple analysis were found according to the EU (7)-PIM list. Perhaps an association with the use of PIMs would have been expected for arrhythmias due to the high prevalence of apixaban. In previous research, the observed associated factors varied from study to study, and this might be the result of different study locations and study samples even though the same identification tool was used [
6,
26,
27]. However, the reason for the lack of significant associations in the present study might be due to the small study sample.
Strengths of the study are the fact that the medication records used are a reliable source, and as far as we are aware the present study is also the first study that compares the prevalence of PIMs using both the EU (7)-PIM list and the Swedish quality indicators.
There are some limitations to consider with the present study. First and most important, the number of patients included was limited. Thus, the representativeness of the study population is low and the results should be interpreted carefully because there is risk of bias and chance findings. Also, the chance to find statistically significant relationships is very low due to the limited number of observations, and the results should be interpreted with caution for that reason as well.
A new version of the Swedish quality indicator was used in the analysis, a version that was not published when the data were collected, and this has to be taken into account when interpreting the results. Among substances prevalent in the study population, glibenclamide and codeine were not listed in the version from 2010, the list that was valid in 2015–2016 when data was collected. Also, the use of antipsychotic medications and NSAIDs were included in the quality indicators, although the indications for prescribing were not assessed. Further, a total of 282 substances are identified as PIMs according to the EU (7)-PIM list, but only 137 substances were evaluated in this present study because many of the medications are not approved for use in Sweden. The duration and regimen-dependent PIMs and pro re nata medications were also excluded, which might lower the prevalence of PIMs among the study population according to the EU (7)-PIM list.
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