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ORIGINAL ARTICLE
Year : 2021  |  Volume : 24  |  Issue : 11  |  Page : 1719-1727

Inappropriate drug use rates of geriatric patients attending to a university hospital cardiology policlinic


1 Department of Family Medicine, Denizli Fatih Family Healthcare Center, Denizli, Turkey
2 Department of Family Medicine, Eskişehir Osmangazi University, Eskişehir, Turkey
3 Department of Cardiology, Eskişehir Osmangazi University, Eskişehir, Turkey

Date of Submission13-Oct-2020
Date of Acceptance04-May-2021
Date of Web Publication15-Nov-2021

Correspondence Address:
Dr. Y E Sari
Denizli Fatih Family Healthcare Center, Denizli
Turkey
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/njcp.njcp_517_18

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   Abstract 


Background: The interest in risks related to inappropriate drug use (IDU) and polypharmacy among the elderly has increased in recent years. Aims: We aimed to determine the frequency of IDU and multiple drug use in elderly patients in the cardiology outpatient clinic. Patients and Methods: In this prospective, cross-sectional study, a total of 513 patients aged 65 years and above who were admitted to the Cardiology Policlinic between December 2017 and January 2018 were included. To determine the prevalence of IDU, we investigated the suitability of the drugs used by the patients (according to the criteria of Beers 2015 and Screening Tool of Older People's Prescriptions [STOPP] version 2), the number of violated criteria in both the guidelines and which criterion was violated by the inappropriate drugs. Results: The 513 patients (mean age: 73.18 ± 5.99) in this study included females (n = 235; 45.8%) and males (n = 278; 54.2%). A total of 2,910 drugs were used by the 513 patients (mean per patient: 5.67 ± 2.51); 52.8% of the patients were using more than five drugs. The Beers criteria revealed that 304 IDUs were detected among the drugs and showed that 38.6% (n = 198) of the patients had IDU. According to the STOPP criteria, 366 IDUs were identified among the drugs used, and 45.6% (n = 234) of the patients had IDU. Conclusion: IDU frequencies of the elderly patients are similar to the world literature in our study. As the number of chronic illnesses the patients had increases, the frequency of IDU increases according to Beers and STOPP criteria in our study.

Keywords: Beers criteria, cardiology, polypharmacy, STOPP criteria


How to cite this article:
Sari Y E, Unluoglu I, Cavusoglu Y, Bilge U. Inappropriate drug use rates of geriatric patients attending to a university hospital cardiology policlinic. Niger J Clin Pract 2021;24:1719-27

How to cite this URL:
Sari Y E, Unluoglu I, Cavusoglu Y, Bilge U. Inappropriate drug use rates of geriatric patients attending to a university hospital cardiology policlinic. Niger J Clin Pract [serial online] 2021 [cited 2021 Nov 28];24:1719-27. Available from: https://www.njcponline.com/text.asp?2021/24/11/1719/330467




   Introductıon Top


The elderly population (≥65 years) is increasing globally, both in numbers and percentage-wise. It is estimated that at present there are 146 million people aged 65 years or older in the developed countries, and the number is expected to reach 1.4 billion by 2030.[1],[2] Similarly, the interest in the risks related to inappropriate drug use (IDU) and polypharmacy (multiple drug use) among the elderly has increased in recent years. Although polypharmacy is defined differently by various sources, it often entails the use of five or more drugs simultaneously.[3],[4] It is potentially hazardous and can result in inappropriate use, dosing, side effects, falls—due to drug interactions, and hospitalization.[5] This stems from the fact that the incidence of side effects and drug interactions multiplies exponentially with the use of multiple drugs.[5],[6] Furthermore, as a natural consequence of aging, alterations in the metabolism and excretion of drugs increase the risk of side effects in the elderly. Approximately 30% of all hospitalizations result from problems related to medication.[7] In this regard, IDU involves situations where drugs have unacceptable side-effect profiles, significant interactions with other drugs, and therefore, it necessitates close monitoring, or—in its absence—providing a better alternative, or eliminating those without an indication.[8]

Due to the high incidence of cardiovascular diseases (a chronic disease) among elderly patients, cardiology outpatient admissions are high. These patients may have conditions such as arrhythmia, blood pressure problems, syncope due to side effects of drugs, and IDU. We aimed to determine the incidence of IDU and multiple drug use in the elderly patients at a cardiology policlinic according to the Beers 2015 and Screening Tool of Older People's Prescriptions (STOPP) version 2, criteria.


   Methods Top


We obtained approval from the Non-Interventional Clinical Investigations Ethics Committee of Eskişehir Osmangazi University to conduct this prospective, cross-sectional study among 513 participants. The inclusion criteria were admission to the cardiology polyclinic of the Eskişehir Osmangazi University Health Practice and Research Hospital between December 2017 and January 2018; aged 65 years and over; voluntary participation; and no cognitive disorders.

Measures

The patients' sociodemographic characteristics, comorbidities, the number of drugs used, and the interaction between them were examined for significance.

Sociodemographic characteristics and patient details

The following information was noted on the observation form for each patient: age, gender, marital status, education status, occupational status, additional diseases, number of drugs used, and names of drugs used.

Beers and STOPP

To determine the prevalence of IDU, we investigated the suitability of the drugs used by the patients (according to the criteria of Beers 2015 and STOPP version 2), the number of violated criteria in both the guidelines and which criterion was violated by the inappropriate drugs. Many studies have used the Beers and STOPP criteria to assess IDU in elderly patients.[9],[10]

2015 Beers criteria

Beers criteria were first used by Beers et al. It was developed in 1991 in order to evaluate the drugs used by the elderly living in nursing homes. These criteria, which have been used for nearly 30 years to minimize inappropriate drug use (IDU) in the elderly population, were updated in 1997, 2002, 2003, and 2012. It was updated by the American Geriatric Society (AGS) in 2015 to provide more comprehensive information about the drug-related problems and adverse drug events in older adults. The purpose of the criteria is to improve drug selection, educate clinicians and patients, reduce adverse drug events, assess care, cost, and drug use patterns of the elderly, and minimize exposure of the elderly population to the IDU.[10],[11],[12]

STOPP criteria

STOPP criteria were used for the first time in 2008 by O'Mahony D et al.[9] for comparison with the Beers criteria and by the multidisciplinary committee. It was prepared by taking into consideration criteria such as drug-drug, drug-disease interaction, causing falls in the elderly, and duplication of drugs in the same group.

Statistical analysis

Continuous data were presented as mean ± standard deviation and median (Q1–Q3), and categorical data as percentages (%). We used the Shapiro–Wilk test to investigate the accordance of the data to the normal distribution, and a sample t-test independent of normal distribution tests to determine the difference between the two groups of continuous variables by independent sample t-test from normal distribution tests. Cohen's kappa test was used to determine the level of agreement; agreement and similarity of the violation criteria. Spearman's correlation coefficients were calculated to determine the direction and magnitude of the correlation between the variables, and for the variables that did not show a normal distribution. The analysis was completed using SPSS 21.0 (IBM, Armonk, NY). Statistical significance set at P < 0.05 was considered important.


   Results Top


The 513 patients (mean age: 73.18 ± 5.99) in this study included females (n = 235; 45.8%; mean age: 73.14 ± 5.88) and males (n = 278; 54.2%; mean age: 73.21 ± 6.09). There was no significant difference between the average age for males and females (P = 0.905). Among the participants, 82.8% (n = 425), 10.9% (n = 56), 3.7% (n = 19), and 2.5% (n = 13) were married, widowed, divorced, and single, respectively. Furthermore, 5.5% (n = 28), 56.1% (n = 288), 30.8% (n = 158), and 7.6% (n = 39) were illiterate, primary school, high school, and higher education graduates, respectively. Concerning occupational status, 0.8% (n = 4), 5.8% (n = 30), 1.2% (n = 6), 50.7% (n = 260), and 41.5% (n = 213) were in the private sector, traders, farmers, retired, and homemakers, respectively.

In terms of comorbidities, between 0 and 9 (median = 3.00 [2.00–4.00]) of the following diseases were noted in the order of prevalence: hypertension (HT; 63.5%); coronary artery disease (CAD; 52.0%); hyperlipidemia (39.8%); diabetes mellitus (DM; 30.6%); atrial fibrillation (AF; 26.1%); gastrointestinal system diseases (18.1%); heart failure (HF; 14.8%); hypothyroidism (10.1%); chronic obstructive pulmonary disease (COPD; 9.9%); cardiac valve disease (9.0%); mood disorder (7.6%); benign prostatic hypertrophy (4.3%); cerebrovascular accident (4.1%); asthma (2.3%); Parkinson's disease (1.8%); dementia; (1.2%); and Alzheimer's disease (0.4%).

Somewhat surprisingly, a total of 2,910 drugs were used by the 513 patients (mean per patient: 5.67 ± 2.51; median: 6.00 [4.00–7.00]). Among the patients, 45.4% (n = 233) and 7.4% (n = 38) used between 6 and 9 drugs (polypharmacy) and 10 or more drugs (excessive polypharmacy), respectively. There was a significant relationship between the number of medications used by the patients and their age (r = −0.107, P = 0.015).

Furthermore, the Beers criteria revealed that 304 IDUs were detected among the drugs and showed that 38.6% (n = 198) of the patients had IDU. According to the STOPP criteria, 366 IDUs were identified among the drugs used, and 45.6% (n = 234) of the patients had IDU. The comparison of the number of criteria violated, according to the Beers and STOPP measures, according to the number of the patients, is shown in [Table 1].
Table 1: Potentially inappropriate medication according to Beers and STOPP version 2 criteria

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According to [Table 2], 66.7% of the 198 patients who violated the Beers criteria also had a violation of STOPP criteria and 56.4% of the 234 patients with a violation of STOPP criteria also had a violation of Beers criteria. When the accordance of the Beers and STOPP criterion violation assets was examined, it was found that there was a low level of accordance, but this fit was statistically significant (Cohen's kappa = 0.332; P < 0.001).
Table 2: Compliance of Beers and STOPP criteria violations

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There is a significant relationship between the total number of comorbidities and the number of violations of the Beers criteria and the STOPP criteria. As the number of additional diseases increases, the number of criteria violated in both the criteria groups increases [Table 3].[13]
Table 3: Relationship between the number of additional diseases and the number of violations of Beers and STOPP criteria

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Our results also indicate that the most frequently used drugs are aspirin and non-cyclooxygenase (non-COX) selective non-steroidal anti-inflammatory drugs (NSAIDs) in 7.8% (n = 40), digoxin in 5.3% (n = 27), peripheral alpha-blockers in 4.9% (n = 25), and strong anticholinergics and nifedipine in 3.3% (n = 17) of the patients [Table 4] and [Table 5]. Furthermore, the most frequently violated drug groups are related to the cardiovascular system (15.8%) and pain medication (9.2%) [Table 4].
Table 4: Usage status of potentially inappropriate medications that should be avoided in the elderly

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Table 5: Usage status of potentially inappropriate medications that should be used with caution in elderly adults

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Moreover, the Beers criteria indicate that among the potentially important clinically non-anti-infective drug-drug interactions that should be avoided in elderly adults, the warfarin-NSAID group (4.1%) [Table 6] most frequently violates the interactions criteria. The most frequently violated STOPP criteria relate to antiplatelet/anticoagulant drugs, musculoskeletal drugs, cardiovascular system drugs, duplication, and medications that increase the risk of falling and occur among 28.5% (n = 146), 8.6% (n = 44), 6.0% (n = 31), 4.7% (n = 24), and 4.1% (n = 21) of the participants, respectively [Table 7]. The most duplicated drugs are the diuretic group, respiratory system anticholinergics, respiratory system glucocorticoids, and beta blockers in 41.7% (n = 10), 12.5% (n = 3), 8.3% (n = 2), and 8.3% (n = 2) of the patients, respectively.
Table 6: The frequency of clinically potentially important non-anti-infective drug-drug interactions that should be avoided in elderly adults

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Table 7: Distribution of violated criterion according to STOPP criteria

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   Dıscussıon Top


Polypharmacy and IDU are important concepts that are commonly encountered globally. They increase the financial burden and decrease the quality of health in populations.[14],[15] By using the Beers 2015 and STOPP version 2 criteria, we aimed to determine the incidence of IDU in elderly patients who were admitted to a cardiology polyclinic. Our data revealed that chronic diseases and related mortality rates are increasing in parallel with the growing elderly population internationally. In 2016, circulatory system diseases were the most common causes of mortality in people aged 65 years and over in Turkey. Among these diseases, ischemic heart disease was the most common.[16]

In their 2016 American study involving 404 cases, Sheikh-Taha and Dimassi found that the chronic diseases among cardiology patients were HT (75%), dyslipidemia (52.2%), CAD (49.5%), HF (41.8%), AF (35.9%), DM (35.4%), chronic renal failure (28.5%), and COPD (20.8%).[17] Somewhat similar, we found that the incidence of chronic diseases was the highest for HT, CAD, dyslipidemia, DM, AF, gastrointestinal system diseases, HF, hypothyroidism, and COPD in descending order.

In terms of polypharmacy among the elderly, our findings were similar to the many related studies that have been conducted worldwide. Considering its high global occurrence, polypharmacy seems to be an international health issue.[18],[19] In this regard, Lesende et al.'s[20] 2013 cross-sectional study showed an IDU frequency of 55% according to STOPP criteria and Hudhra et al.'s[21] cross-sectional Spanish study (2015) recorded a 54% frequency having used the same criteria. Interestingly, Zhang et al.'s[22] 2017 retrospective, cross-sectional study among 456 patients in China, showed a IDU frequency of 53.5% according to Beers 2015 criteria. However, it appears that IDU frequency varies per country, study type, patient group, and IDU identifying criteria. The variance in treatment modalities, drug forms, lifestyles, and chronic disease profiles between countries can also cause different results. In our study, the IDU frequency was 38.6 and 45.6% according to the Beers 2015 and STOPP criteria, respectively, which is similar to the literature.[17],[20],[21],[22]

In Bahat et al.'s[18] study, the most commonly observed IDU profiles per the Beers (2012) criteria were antipsychotics (29.4%), SSRI (14.4%), NSAIDs (9.3%), alpha-blockers (8.0%), digoxin (5.3%); while the STOPP criteria highlighted aspirin (14.8%), antipsychotics (13.9%), anticholinergics (13.0%), loop diuretics (9.5%), and verapamil/diltiazem (4.2%). We found that aspirin and non-COX selective NSAIDs (7.8%), digoxin (5.3%), peripheral alpha-blockers (4.9%), strong anticholinergics, and nifedipine (3.3%) were the most frequent inappropriately used drugs, while the cardiovascular system (15.8%) and pain medications (9.2%) were the most frequently violated criteria groups when the IDU profiles were examined according to the Beers 2015 criteria. Among the drug-drug interactions that should be avoided in elderly adults, the Warfarin-NSAIDs group was the most frequently violated interaction group. By applying the STOPP criteria to IDU profiles, the most commonly seen drug groups were antiplatelet/anticoagulant drugs (28.5%); musculoskeletal drugs (8.6%); cardiovascular system drugs (6.0%); duplication (4.7%); and drugs that increase the fall risk in the elderly (4.1%). A total of 41.7% of the duplicated drugs were in the diuretics group. We think that there were more cardiovascular-related IDU profiles because our study was conducted at a cardiology clinic.

Apart from aspirin and NSAIDs having been used inappropriately most frequently, the incidence of inappropriate consumption of antiplatelet agents and anticoagulants was also high. Low-dose aspirin is commonly used by elderly patients to reduce thromboembolic events.[23] Aspirin effects are dose-related, and the side effects are mostly related to the gastrointestinal system. Moreover, the use of antithrombotic or anticoagulant medication in combination with aspirin increases the risk of gastrointestinal side effects, among which epigastric pain, hemorrhage, dyspeptic complaints, tinnitus, and allergic reactions are the most common.[24] Proton Pump Inhibitors (PPIs) should be added to the treatment to reduce the risk of ulcers and gastrointestinal bleeding in patients with a high risk of gastrointestinal bleeding.[25] In addition to gastrointestinal and renal side effects, NSAID use has hematological, cardiovascular, pulmonary, allergic, and dermatological side effects. Gastrointestinal side effects include dyspeptic complaints, abdominal pain, ulcer formation, associated bleeding, and perforations.[25]

The renal side effects with the use of aspirin and NSAIDs—mainly hypertension, renal insufficiency, and reduced efficacy of antihypertensive drugs—could present as interstitial nephritis, nephrotic syndrome, acute renal failure, acute tubular necrosis,[26],[27] prolonged bleeding, anemia, hyperkalemia, worsening of asthma symptoms, urticaria, and Steven–Johnson syndrome.[27] The combination of NSAIDs with Warfarin, direct thrombin inhibitors, and Factor Xa inhibitors is not recommended since it increases the risk of gastrointestinal bleeding. It should be used in combination with a PPI.[9]

In general, NSAIDs are one of the most frequently prescribed drug groups. However, its use in patients with a history of myocardial infarction is associated with a high risk of cardiovascular events. These medications should be used with caution in patients with stable heart disease. Furthermore, short-term use of these drugs at the lowest dose is recommended. COX-2 selective drugs should be the last choice.[28] We also propose that drug selection should be done according to the individual's clinical situation, thereby individualizing the dose and treatment. In addition, treatment should be performed at a low dose with regular monitoring.

In the study, the inappropriate use of digoxin according to the Beers criteria was 5.3%. Digoxin, which has a narrow safety margin, is a cardiac glycoside used for rate control in patients with HF and AF, and its side effects can be acute or chronic. Toxic symptoms – mostly nausea, vomiting, weakness, loss of appetite, diarrhea, and restlessness – start appearing when the digoxin blood serum levels rise above 2 ng/mL. The rhythm disorders caused by digoxin play an important role in the prognosis. Commonly seen rhythm disorders include atrioventricular (AV) block, sinus bradycardia, slow ventricular responsive AF, AV blocks accompanying rapid atrial and ventricular rhythms secondary to the increase in automatism. Since digoxin has a high volume of distribution in the body, determining the blood digoxin level alone is not sufficient and the patient should be evaluated under clinical conditions to determine the degree of side effects and toxicity thereof.[29],[30]

There was 4.9% inappropriate use of peripheral alpha-blockers according to the Beers criteria in the study. Alpha-blockers, another widely inappropriately used drug group, present side effects including orthostatic hypotension, headache, dizziness, weakness, and reflex tachycardia due to their vasodilating effect. There is a risk of falls and hip fractures in the elderly resulting from orthostatic hypotension. Peripheral resistance is reduced, and reflex tachycardia may develop due to the alpha receptor blockade. The riskiest alpha blocker for the development of tachycardia is doxazosin. Furthermore, the use of alpha-blockers alone as monotherapy in patients with hypertension is not recommended due to the risk of developing congestive HF. In addition, terazosin and doxazosin are not recommended for use in severe hepatic failure, but tamsulosin has a wider safety margin. For these reasons, alpha-blockers are not the first choice for the treatment of hypertension but could be used in those with a history of prostatism.[31]

In addition, in our study, 3.3% had inappropriate use of nifedipine. In terms of nifedipine, its use in geriatric patients is not recommended due to the risk of hypotension and myocardial ischemia. It also has potential side effects including congestive HF due to systolic dysfunction, deterioration in glucose tolerance, constipation, edema in the lower extremities, negative inotropic effect in the presence of cardiac failure, gastroesophageal reflux, and increased blood levels of digoxin. Sublingual nifedipine administration is not recommended for emergency hypertension treatment because of the sudden drop in the tension that may occur.[24],[32],[33],[34]

In the study, there was a similar rate of inappropriate use of anticholinergic drugs with nifedipine. In the case of inappropriate use of anticholinergic drugs or overdosage, a condition called anticholinergic toxicity can occur. The main symptoms and signs include flushing, drying of the skin, mydriasis, fever, unexplained fluctuating consciousness, urinary retention, hypertension, and sinus tachycardia. Many drugs (antipsychotics, anti-Parkinsonian drugs, antispasmodics, opiate analgesics, tricyclic antidepressants, antiemetics, psychotropic drugs, and skeletal muscle relaxants) with anticholinergic effects are commonly used in the elderly. Interestingly, some plants and fungi may also have anticholinergic effects, but the use of anticholinergic drugs should be questioned in patients with unexplained fluctuation of consciousness. Again, side effects and interactions should be considered when treating elderly patients.[35] In general, IDU is more frequently observed in elderly patients because of the multiple health problems they have. Age-related changes concerning pharmacokinetics and pharmacodynamics should be considered when prescribing any drug.[34]

In the study, violation rates were different according to the Beers and STOPP criteria. Although Beers and STOPP criteria groups have similar sides, they generally approach inappropriate drug prescribing from a different perspective. We think that the rates are different because we cannot examine each criterion due to some limitations we have mentioned in our study. As stated in the Results Section, although the accordance between the criteria is low, it is statistically significant (P < 0.001).

Concerning our recommendations above, it needs to be noted that patients with comorbid cardiological diseases often use drugs. However, the treatment dosage should be individualized, commenced, and followed closely, in accordance with guidelines, while considering possible side effects and drug interactions.


   Conclusıon Top


The number of drugs used, the polypharmacy rates, and IDU frequency of patients 65 years and over who were admitted to the cardiology polyclinic of Eskişehir Osmangazi University Health Practice and Research Hospital were similar to the international research findings. Moreover, the number of chronic illnesses in the patients increased with the IDU frequency according to the Beers and STOPP criteria in our study. In addition, the number of drugs used increased significantly with age. These guidelines aim to help, not direct, the treatment offered by the physicians. To prevent drug-related side effects, hospitalizations, and mortalities, the patients' treatment must be regulated, all prescripted and non-prescripted drug lists reviewed, and the treatment regimen—appropriate for the age and physiology of the individual—be regulated. The prevention of polypharmacy and IDU is important for the individual and society because of the health problems they cause.

Limitations of the study

As we conducted the study in a polyclinic setting, it was impossible to obtain all the chronic disease information. Some patients' data (including glomerular filtration rate and systolic ejection fraction) could not be obtained; others could not recall how long they have been taking the drugs (including PPIs, benzodiazepine, and corticosteroids) and the inaccessibility of regular test results, such as sodium (Na) and potassium (K) required for follow-up of certain medicines. Due to these limitations, some of the Beers and STOPP criteria were not examined.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]



 

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