PRESCRIPTION FREQUENCY OF MEDICATION CONSIDERED TO BE POTENTIALLY INAPPROPRIATE TO ELDERLY

Abstract

Some medications are considered potentially inappropriate for the elderly, due to changes in the pharmacokinetics and pharmacodynamics that occur in the body, representing risks that outweigh the benefits. Were used the Beers criteria, 2012, Screening Tool of Older Person’s Prescription (STOPP) and Screening Tool to Alert to the Right Treatment (START). It was verified the prevalence of potentially inappropriate medication use by the elderly who attend the Hospital Santa Casa de Misericordia de Vitoria – ES, in an observational, analytical, cross-sectional study with a sample of 150 elderly, mostly made up of women, 70% (105 ) and an average of 72 ± 7 (62-92) years old. 52.7% (79) had IPF use, these 34.7% (52) 12.7% (19) 5.3% and (8) patients were using one, two or three PIMs, respectively. The most prevalent comorbidities were hypertension (82.6%), followed by type 2 diabetes mellitus (23.3%). Stood out depression in the use of potentially inappropriate drugs, and congestive heart failure as polypharmacy. The average of prescribed drugs was 4.69 per elderly. It was verified polypharmacy in 66 elderly (44%). Most potentially inappropriate medication acts on the central nervous system, and then in the cardiovascular system. In isolation, the potentially inappropriate medication more used was aspirin. An association between polypharmacy and polipatologias with the use of potentially inappropriate medications was verified. Thus, it was observed that the patients included were taking a large number of drugs considered potentially inappropriate and the association with polypathologies made them vulnerable to suffering serious adverse events harmful to health.

Keywords

Aged; Drug Prescriptions; Inappropriate Prescribing; Polypharmacy; Health of the Elderly

Introduction

Population aging is considered to be the major risk factor for the development of different diseases. Eldery people often carry multiple chronic non-communicable diseases; therefore, they make concurrent use of many medication prescriptions and it characterizes polypharmacy. More than half of the western world medications are consumed by individuals in this age group.¹

Advancing age is directly connected to changes in drug metabolism, both in the pharmacodynamics  and in pharmacokinetics. It is caused by the aging physiological process, which is represented by gene expression changes, oxidative injuries and mitochondrial dysfunction.²  Such changes are associated with increased drug serum concentration, with reduction in its effectiveness and with higher risk of adverse events and side effects.³

Research on modern drugs rarely selects frail elderly with or without comorbidities for clinical trials. However, these are the individuals who will take most of the medication with the potential to be often inappropriately prescribed. Such gap in the research results in lack of clinical evidence on the efficacy and damages caused by the use of medications in this group of patients. Thus, it forces physicians to just rely on post-marketing data to determine the consequences of medications prescribed to elderly. A key consideration to optimize elderly medication results is the awareness of aging effects on drug metabolism.⁴

Such gap was fulfilled by the Beers’ criteria, which have dominated the international literature since they were first described in 1991.⁵ These criteria were revised in 1997, 2003 and, most recently, in 2012 by the American Geriatrics Society (AGS). It was done in order to overcome the existing gap. The criteria were established by Delphi consensus and have been described by the Screening Tool of Older Person’s Prescription (STOPP) and the Screening Tool to Alert to the Right Treatment (START).⁶ These criteria aim to help better selecting the drugs prescribed to geriatric patients as well as to evaluate and guide dosage standards, PIMsrove elderly care quality, reduce expenses with drugs and to use epidemiological data for research.⁷

Thus, the current study evaluated the presence of potentially inappropriate medications (PIMs) prescription among elderly assisted in clinics or hospitalized at Hospital Santa Casa de Misericórdia de Vitória (HSCMV), according to the Beers’ criteria and the the START / STOPPPIMS.

METHODS

Observational, descriptive and analytical study applied to a cross-sectional sample (n= 150) of elderly (60 years or older) from both genders assisted in ambulatory care or hospitalized at Hospital Santa Casa de Misericórdia de Vitória – Espírito Santo State. The sampling group was set by random selection in different hospital departments, from October 2014 to February 2015.

Data were obtained through interviews with patients (during medical appointments) in ambulatory care or at the admission in the institution.  After clarifying the study’s goals, participants signed the Informed Consent (IC) form which was previously approved by the Research Ethics Committee (CEP- Comitê de Ética em Pesquisa – EMESCAM). If the patient had no new medical prescription in hands, the medications already in use were not recorded. In case the person accompanying the patient had questions about the medication, the patient would be excluded from the analysis.

The dependent variable ‘potentially inappropriate medications (PIMs)’ was classified according to the latest (2012) Beers’ criteria version and to the STOPP and START.^5,6 The independent variables were: age, gender, medications, polypharmacy (regular use of five or more drugs) and polipathology (the presence of three or more comorbidities).

The sample size was randomly calculated, since there are little epidemiological studies in Brazil about potentially inappropriate medication prescription to elderly. The sample consisted of 150 patients aged 60 or older (by convenience) and it was considered to be representative (51 hospitalized patients and 99 ambulatory care patients). Descriptive analysis and association of variables were used for data analysis according to their distribution. They were employed in chi-square test and logistic regression expressed as odds ratio (OD) in 95% confidence interval. The SPSS 22.0 for Windows software was used for data analysis; significance level ≤ 0.05 were taken under consideration.

RESULTS

One hundred fifteen (150) elderly – predominantly women (70%) – mean age 72 ± 7 (62-92) years were analyzed. Fifty two point seven percent (52.7%), (79 individuals) of them depended on PIMs; out of these 52.7%, 34.7% (52 individuals), 12.7% (19 individuals) and 5.3% (8 individuals) were taking one, two or three PIMs, respectively. Polipathology was found in 43.3% (65 individuals) of the population and Polipharmacy in 44% (66 individuals). Women showed 56.2% (59 individuals) and 46.7% (49 individuals); and men showed 44.4% (20 individuals) and 37.7% (17 individuals) of PIMs and Polipharmacy, respectively (c² 1,743, p = 0.21).

When PIMs and polipharmacy were stratified by age group, it was respectively found: 60-69 years (59 individuals), 52.4% (31individuals) and 42.3% (25 individuals); 70-79 years (66 individuals), 54.5% (36 individuals) and 46.9% (31 individuals); and older than 80 years (25 individuals), 48% (12) and 40% (10), as shown in Table 1.

Table 1: Logistic regression (95% confidence interval) for the age groups:

The most often comorbidities out of the 44 found in the analyzed sample were: Systemic arterial hypertension (HT) (124/82.6%), type 2 Diabetes mellitus (DM2) (41/23.3%), Dyslipidemia (30/20%) and Neoplasia (27/18%), represented shown in Table 2.

Table 2: Comorbidity Frequency:  average of 2.48 pathologies per patient.

* Gastroesophageal Reflux Disease

Among the aforementioned comorbidities, HT presents the highest prevalence and it was found in 58.06% of patients with PIMS and in 47.58% of those with polipharmacy. DM2 is the second most common comorbidity and it features more relevant numbers, 70.73% of the cases present PIMs or polipharmacy. CHF stands out for its strong relation with polipharmacy (88.89%). Depression is the comorbidity mostly associated with PIMs, it was found in 88.89% of patients (Table 3). The comparative study between polipharmacy and polipathology and PIMs revealed the association shown in Table 4. Table 5 shows the most used medications in the herein studied age group.

Table 3: Polipharmacy and potentially inappropriate medications for certain comorbidity

Table 4: Polypharmacy and polipathology association with potentially inappropriate medication prescription (PIMs)

Table 5: Organic system, therapeutic category or inappropriate medications prescribed by age group

*In evidence of peptic ulcer, dosage higher than 150 mg / day, with no indication of secondary prevention.

** Higher dose than 25 mg / day, *** First-line treatment for hypertension.  NSAIDs, Angiotensin-Converting-Enzyme Inhibitors (ACE Inhibitors), Angiotensin II receptor blockers (ARBs).

Discussion

Findings in the present study show that more than half of the elderly (52.7%) in ambulatory care or hospitalized were continuously taking potentially inappropriate medications and it could result in negative PIMsacts. According to recent meta-analysis published by Sichieri et al. (2013) involving 90.611 patients, revealed that PIMS consumers presented higher mortality risk, regardless of drug type, comorbidity and polypharmacy.⁸

Previous investigations concerning PIMs prevalence reported values between 21.7% and 48%.^9-14. However, it is difficult to evaluate the comparison among results if one takes into consideration that prevalence rates in different populations change according to the time and place data were collected and the used collection criteria.¹⁵ The present study used a combination of Beers’ criteria (2012 version) and STOPP and START in PIMS detection; although, most epidemiological publications in the literature have used Beers’ criteria (2003 version), since the 2012 update is still very recent.

Result variability can be elucidated through the publication by Gallagher et al. (2011), who developed a parallel between the PIMs found in six European hospital admissions. According to the adopted criteria, they have obtained 30.4% PIMS according to Beers; 51.3%, to STOPP; and 59.4%, to START.¹⁶

PIMs difference by gender showed no statistical significance in the current study, as well as in part of the reviewed studies.¹⁷ However, it disagrees with the literature, since other studies and a bibliographical review showed higher PIMs prevalence among women.^11,12,18Accordingly, polipharmacy was not significantly correlated with gender; however, there was the tendency of higher average of drug prescriptions among women; the same results were observed in Brazil and in other countries.¹⁹ Biological issues are the justification found in published articles for the higher prevalence of PIMS and polipharmacy among women, since they are more prone to nonfatal health problems. Socio-cultural issues and the concern with physical and psychological symptoms make women tend to look for healthcare services more often than men. Women are also more familiar with medications.¹²

PIMs risk suffered no statistical influence from the patients’ age; although slightly higher rate of it was found among those over 80 years old. There is also no consensus in the literature about whether the use of PIMSs gets more or less often as the patient ages. Thus, different studies with different age groups point to higher and lower PIMs rates.¹¹

Individuals with Depression (88.8%), Gastroesophageal reflux disease (80%), congestive heart failure (77.7%), Coronary disease (76.9%) and Diabetes mellitus (70%) showed higher PIMs frequency. Depression presented the highest PIMs rate – considering that most of CNS drugs (such as benzodiazepines, tricyclic antidepressants and antipsychotics) are indicated to its treatment. It is PIMsossible to compare polipharmacy and PIMs due to comorbidity in other articles because of its absence in in them.

Sixty five point eight percent (65.8%) of PIMs patients just take one drug; 24.1%, two; and 12.1%, only three, which is the maximum amount consumed by a single patient. A study performed in São Paulo showed that 83.8% of PIMs patients just consumed one drug; 13.8%, two; and 2.4%, took three to five drugs.¹¹

In terms of organic system drugs more commonly associated with PIMs there was the predominance of CNS (40.4%) and it was followed by cardiovascular drugs (36.0%). A study conducted in São Paulo (2012) showed similar profile, 53.4% were drugs acting in CNS and it was followed by 32.0% of cardiovascular system drugs. ¹³ Another study published in Brazil pointed towards the higher frequency within the cardiovascular group.¹² It is justified by the fact that this is the most frequently therapeutic class of drugs used by elderly, given the high prevalence of cardiovascular diseases among the Brazilian population; as it was observed in the present study (SH, CAD, CHF).²⁰

The six most prescribed medications, in order of frequency, according to the herein employed criteria were ASA, clonazepam, glibenclamide, diazepam and bromazepam – evenly matched – alprazolam, spironolactone and furosemide. It represents over 56% of the potentially inappropriate medications for elderly. A recently published Brazilian study found 42 different drugs. A review of 440 medical files showed  metoclopramide, ketoprofen, ASA, insulin, ipratropium bromide, and clonazepam as the most commonly prescribed medications (64% of total PIMs).²¹

Benzodiazepines belong to the therapeutic class with the highest number of PIMs.  Clonazepam is their major representative and second most prescribed drug in the entire study. They are considered to be inappropriate according to the herein used criteria, since these drugs have long half-life in elderly patients (usually for several days), thus producing prolonged sedation; fact that can increase fall events and fracture risk with possible severe consequences. The significant frequency of benzodiazepine use reported in Brazilian studies, including The SABE Study (Health, Wellbeing and Aging survey), may be related to its low cost and availability, as it is supplied by the National Health System SUS ( Sistema Único de Saúde) for free.¹² Moreover, it is one of the most often prescribed drugs for treating insomnia – condition often observed in elderly, due to sleep disorders.²²

The higher NSAIDs PIMs frequency in the younger age group can be associated to the better quality of life provided by these drugs to chronic pain patients. Such pain is caused by morbidities such as arthritis, cancer and orthopedic fractures. There will likely be greater tolerance by physicians regarding the use of these medications among this age group, regardless the risk of kidney damage and gastrointestinal bleedings.²³

The average of prescribed medications per interviewed patient was 4.69. This value is slightly above those found by other surveys conducted in Brazil which found values ranging from 1.3 to 4.3 drugs per patient.^20,24 However, the value is lower than that found in the descriptive observational study (7.5) by the Geriatrics Service of Hospital das Clinicas in São Paulo.¹¹ Another investigation – done in an American database – with 965.756 patients aged 65 years or older,  found that mean number of prescribed items  of  7.2 per patient.²⁵

The association between polypharmacy and polipathology with the use of potentially inappropriate medications found in the current study is not surprising, since the use of multiple medications is also highlighted as a factor associated with PIMs in several Brazilian and foreign studies.^10,14,16,17A recent systematic review showed polypharmacy as the variable most strongly associated with PIMs use, as it was also herein found. It was proved that the use of several drugs can expose elderly to substances whose risks outweigh their benefits.¹⁸The present study described the presence of polipathology as an association with PIMs in less than half of the studied population. Other authors also reinforce this point by stating that elderly with the biggest number of comorbidities are those presenting higher medication need and, therefore, higher PIMs risk.¹⁶ Thus, it is crucial to evaluate the prescribed pharmacotherapy and analyze each case individually, since, according to the systematic review, PIMs have been associated with numerous hospital admissions, adverse reactions and increased mortality risk among older age individuals.¹²

By considering the study’s limitation regarding interviewees’ age group, Beers’ criteria were applied to over 65 year old patients. The present study adapted the criteria to Brazilian parameters by taking under consideration the over 60 year old population for the evaluation. However, Beers’ new criteria were recently published and there are just few studies able to comparative analysis. Likewise, there are not many publications about STOPP and START used along with the Beers’ criteria. Data collection and analysis was done through interviews; the limitation factor was lack or omission of pathological history and/or medication use by patients and their companions – medication previously taken could be a confounding factor for PIMs determination.

Conclusion

According to the interviews, it was found that elderly in ambulatory care or hospitalized were regularly taking a big number of drugs considered to be potentially inappropriate for elderly. The risk associated with multiple comorbidities and drugs make these individuals more vulnerable to serious adverse events that have negative consequences to their health and are a burden to the healthcare system.

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Authors

Eduardo Oliveira Pacheco: School of Sciences of Santa Casa de Misericórdia de Vitória (EMESCAM ) (12th semester Medical School undergraduate)

Igor Schneider Faé: School of Sciences of Santa Casa de Misericórdia de Vitória (EMESCAM ) (12th semester Medical School undergraduate)

Cyro Rezende Laghi: School of Sciences of Santa Casa de Misericórdia de Vitória (EMESCAM ) (12th semester Medical School undergraduate)

Lorraine de Souza Juri: School of Sciences of Santa Casa de Misericórdia de Vitória (EMESCAM ) (12th semester Medical School undergraduate)

Renato Lírio Morelato: Adjunct Professor of Geriatrics at the School of Sciences of Santa Casa de Misericórdia de Vitória (EMESCAM ), (Supervisor at the Medical Residency Program in Geriatrics at Hospital Santa Casa de Misericórdia de Vitória , Espírito Santo State)