Polypharmacy, inappropriate medication use and associated factors among brazilian older adults

Polifarmácia, uso de medicamento inapropriado e fatores associados em idosos brasileiros

Abstract

Background

Population aging is still an important worldwide phenomenon. Elderly people suffer from multiple chronic diseases that require the use of several drugs, and this demographic scenario fosters the increased prescription of multiple drugs, or Polypharmacy (PP) and Potentially Inappropriate Medication (PIM).

Objective

This study aimed to identify the prevalence rates and associated factors of PP and PIM in Brazilian older adults.

Method

The prevalence of PIM use and PP was estimated in a sample of 222 patients enrolled in the Family Health Program in Niterói, Brazil. Logistic regression models were used to analyze the data. Age and sex were kept in the models as potential confounding factors.

Results

PP and PIM use presented prevalence rates of 23.9 and 24.8%, respectively. PP was associated with body mass index, coronary heart disease, diabetes mellitus, and a number of comorbidities, whereas PIM use was associated with PP.

Conclusion

The prevalence rates of PP and PIM use found were lower than those reported in previous studies. This could be a result of differences in availability of drugs or prescribing habits. Multiple chronic diseases were associated with PP. These results suggest that more care should be taken in prescribing for the elderly population.

Keywords:
drug therapy; epidemiology; older adults

Resumo

Introdução

O envelhecimento populacional é um fenômeno mundial. Os idosos apresentam mais comorbidades e usam vários medicamentos, cenário que aumenta a prescrição de polifarmácia (PF) e o uso de medicamentos potencialmente inapropriados (MPIs).

Objetivo

O objetivo do estudo foi identificar a prevalência e os fatores associados à PF e aos MPIs em idosos brasileiros.

Método

Foi utilizada uma amostra de 222 idosos inscritos no Programa Médico de Família em Niterói, Brasil (Estudo Digitalis). Foi estimada a prevalência de PF e MPIs. Foram usados modelos de regressão logística. Idade e sexo foram mantidos nos modelos como possíveis fatores de confusão.

Resultados

A prevalência de PF foi de 23,9% e de MPIs 24,8%. A PF foi associada com índice de massa corpórea, doença coronariana, diabetes mellitus e número de comorbidades; já MPIs foram associados com PF.

Conclusão

A prevalência de PF e MPIs, embora elevada, foi menor do que a evidenciada em outros estudos. Isso pode ser reflexo das diferenças na disponibilidade das medicações e nos hábitos de prescrição. A PF foi associada à presença de múltiplas comorbidades, visto que sempre é necessário o uso de várias drogas para a manutenção terapêutica. Os resultados deste estudo demonstram que ainda é preciso maior cuidado na prescrição de pacientes idosos.

Palavras-chave:
tratamento farmacológico; epidemiologia; idoso

INTRODUCTION

Population aging is still an important worldwide phenomenon. In addition, the budget for medical care has been rising not only because of demographic changes, but also because of the need to improve acute care for this specific population group¹. Studies have shown that the number of older adults (aged ≥60 years) in the world is expected to increase by more than double - from 841 million people in 2013 to over 2 billion in 2050². This fact has increased the prevalence of chronic diseases, representing a major challenge for the health care system. Moreover, health care providers work in a culture that facilitates diagnosing and prescribing, paying relatively little attention to de-prescribing or reducing chronic medications. This can lead to overtreatment, drug-related illnesses³ and falls, which are leading causes of injuries, hospitalization, and deaths in older adults⁴.

This demographic scenario has raised the prescription of multiple drugs or Polypharmacy (PP), which is defined in most of recent studies as the concomitant use of five or more medications^5-7. Elderly people suffer from multiple chronic diseases that require the use of several drugs, so they use more drugs per capita than other population strata. An US study conducted with older adults found that an overwhelming majority (73%) of this population with three or more chronic conditions makes use of five or more prescription drugs. Similar drug use was found in Europe, where 62% of the elderly population takes at least six medications per day⁸.

Polypharmacy, combined with changes in liver and kidney metabolism intrinsic to aging, can culminate in adverse drug reactions (ADRs). Up to 10% of hospital admissions among older adults are attributable to ADRs, and 50% of them are avoidable⁹. PP is also often associated with the use of Potentially Inappropriate Medication (PIM), delirium, poor treatment adherence, falls, declines in cognitive and physical functioning, noncompliance with treatment, mortality, and increasing costs to patients and to the health care system^10-12.

This study aimed to evaluate the prevalence of PP and PIM use and associated factors in the elderly population assisted by the Family Health Program in Niterói, Brazil. Recognition of these factors may clarify the conditions under which those problems occur and assist with guiding more appropriate drug prescription. This, in turn, may lead to reduced morbidity, mortality and health care costs.

METHOD

Study sample

Data were collected from a cross-section prevalence study of chronic diseases, the Digitalis study, conducted with patients enrolled in the Family Health Program in the municipality of Niterói, Brazil. The original sample size was composed of 630 individuals aged ≥45 years, and the data were collected between July 2011 and December 2012. This study included all individuals aged ≥60 years who used at least one medication, totaling 222 patients¹³.

During the first visit to the outpatient unit, a structured questionnaire was used to obtain the patients’ clinical history, demographic variables, lifestyle, physical examination, and anthropometric data.

Medication use

All participants were advised to bring their prescriptions to the visit to the outpatient unit. The question asked was “Have you been taking any medication regularly for the past three months?”. In the case of positive response, the patient was asked to show the prescription or the medication box, and information on dosage and frequency was recorded. All drugs were codified accordingly to their active pharmaceutical ingredient and dose. Each medication was then checked using the Beers-Fick¹⁴ and PRISCUS¹⁵ list tables, and if it was included in either of these tables, it was classified as a PIM. Medications were also classified as Antihypertensive (Diuretics, Beta blockers, Angiotensin-converting enzyme inhibitors (ACEI), Angiotensin II receptor blockers (ARBs), Calcium Channel Blockers (CCBs), Vasodilators), Nitrates, Antiarrhythmics, Digitalis, Statins, Hypolipidemic agents, Antidiabetics, Analgesics, Non-Steroidal Anti-inflammatory (NSAIDs), Corticosteroids, Antidepressants, Proton Pump Inhibitors (PPIs), H2 blockers, Anticonvulsants, Anticoagulants, Antiplatelet agents, and Thyroid hormones, and Others. The number of medications per class and the total of medications were counted (within those classes). A cutoff point of five or more medications was used to define PP.

Statistical analysis

The prevalence of PIM and PP among the patients aged ≥60 years who used at least one medication was estimated. Sixteen variables (gender, age, body mass index, skin color, per capita family income, private health insurance, marital status, chronic obstructive pulmonary disease (COPD), coronary heart disease, depression, dyslipidemia, hypertension, diabetes, heart stroke, current smoking status, number of morbidities) were selected as risk factor candidates based on the scientific literature on PP and PIM use^16,17. The age considered was the number of completed years at the moment of the interview. As for marital status, the patient was asked if they had or not a fixed partner. For the variables depression, heart stroke, dyslipidemia and COPD, the patient was asked if these diseases had been diagnosed by any physician. Regarding diabetes, it was considered if the patient had previous diagnosis or treatment of the disease or glycemic levels ≥126 at the moment of the interview. Concerning hypertension, previous diagnostic, use of medication, or high blood pressure at the moment of the interview were considered. With respect to coronary heart disease, angina, myocardial infarction, stent placement, or cardiovascular surgery until the time of interview were considered. As for current smoking status, the patient was asked if they were or have ever been a smoker and if they had smoked at least 100 cigarettes during their lifetime. The number of morbidities for diabetes, hypertension, dyslipidemia, COPD, depression, and obesity were also counted.

All risk factor candidates for PP and PIM (PP was also added as a risk factor candidate for PIM) were included in a simple logistic regression model, and all variables with p-value >0.20 were selected for the stepwise multivariate logistic regression analysis. In the final model, the significance level was set at 5% and age and gender were included as potential confounder variables. Final models had their fit analyzed by residual diagnostics plots (data not shown). Statistical analyses were conducted using the SPSS^® 21 software for Windows^® (IBM/SPSS, Inc., Chicago, IL).

The study was approved by the Research Ethics Committee of the College of Medicine of the Fluminense Federal University under protocol no. 0183.0.258.258.10 and all participants signed a Free and Informed Consent Form prior to data collection.

RESULTS

In the sample composed of 222 patients assisted at the Family Health Program in Niterói, Brazil, the mean age of participants was 69.6 (SD 7.7) years and 152 of them (68.5%) were female. The number of medications prescribed per person varied from 1 to 9 (mean of 3.2), in a total of 712. The mean body mass index (BMI) was 28.1 (5.3): 28.9 (5.4) for females and 26.4 (4.5) for males (p=0.001). Prevalence rates of hypertension, diabetes, and coronary heart disease were 91.4, 36 and 15.8%, respectively. On average, the number the morbidities per person was 2.2.

Prevalence of PP was 23.9% (53 patients) and the prevalence of PIM use, according to Beers-Fick criteria, was 24.8% (55 patients). The PIM prevalence of antidepressants, vasodilators, digitalis and antiarrhythmic users were 55.6% (15/27), 76.9% (10/13), 100% (5/5) and 100% (5/5), respectively (Table 1).

Table 1
Frequency of class medication use and Potentially Inappropriate Medication (PIM) prevalence. Niterói – RJ, Brazil, 2011/2012

Drug class	Medication use frequency	Prevalence of use of PIM %
Antihypertensive	195	10.8
Diuretics	117	0.0
Beta-blockers	51	2.0
ACEIs	109	0.0
ARBs	39	0.0
CCBs	44	45.5
Nitrates	10	0.0
Antiarrhythmics	5	100.0
Digitalis	5	100.0
Vasodilators	13	76.9
Anti-diabetics	58	0.0
Statins	63	0.0
Hypolipidemic agents	5	0.0
Analgesics	4	0.0
Anti-inflammatory	13	23.1
Corticosteroids	8	0.0
Antidepressants/Anxiolytics	27	55.6
PPIs/H2 blockers	39	0.0
Anticonvulsants	3	0.0
Anticoagulants	3	0.0
Antiplatelet agents	49	2.0
Thyroid hormone	8	0.0
Total	222	24.8

• ACEIs - Angiotensin-converting enzyme inhibitors; ARBs - Angiotensin II receptor blockers; CCBs - Calcium Channel Blockers ; PPIs - Proton Pump Inhibitors

Use of PIM was significantly associated with obesity (OR=2.3, p=0.042), PP (OR=4.1, p<0.001), diabetes mellitus (OR=2.8, p=0.001), heart stroke (OR=3.0, p=0.033), and number of morbidities (OR=1.6, p=0.001). After adjustments, PIM use was significantly associated with PP (OR = 4.05, p<0.001) (Table 2).

Table 2
Summary of the logistic regression analysis results for Potentially Inappropriate Medication (PIM) use. Niterói – RJ, Brazil, 2011/2012

	Unadjusted Regression			Adjusted Regression
	OR	CI(95%)	p-value	OR	CI(95%)	p-value
Gender (male/female)	1.48	[0.74; 2.94]	0.265	1.34	[0.65; 2.73]	0.426
Age (years)	0.99	[0.95; 1.03]	0.740	1.00	[0.96; 1.04]	0.994
BMI Classification (WHO)			0.417
Overweight/Under or Normal	1.4	[0.63; 3.08]	0.410
Obese/Under or Normal	1.7	[0.77; 3.92]	0.186
Obesity (Y/N)*	2.31	[1.03; 5.17]	0.042
Skin Color (non-white/white)	1.21	[0.65; 2.28]	0.546
Per capita family income	1.00	[0.99; 1.00]	0.441
Private Health Insurance (Y/N)*	0.73	[0.31; 1.70]	0.466
Marital Status (with/without partner)	0.75	[0.40; 1.39]	0.355
Current Smoking Status (Y/N)*	1.22	[0.66; 2.26]	0.528
Polypharmacy (Y/N)*	4.14	[2.12; 8.07]	<0.001
COPD (Y/N)*	0.59	[0.13; 2.79]	0.508
Coronary Heart Disease (Y/N)*	2.04	[0.95; 4.39]	0.068
Depression (Y/N)*	1.18	[0.56; 2.49]	0.668
Dyslipidemia (Y/N)*	1.10	[0.60; 2.03]	0.755
Hypertension (Y/N)* &	3.00	[0.67; 13.44]	0.150
Diabetes (Y/N)*	2.81	[1.50; 5.25]	0.001
Heart Stroke (Y/N)*	2.99	[1.09; 8.18]	0.033
Number of morbidities	1.60	[1.17; 2.20]	0.001
Poliparmacy (S/N)*	4,14	[2.12; 8.07]	<0.001	4.05	[2.07; 7.93]	<0.001

• ^*
  Y/N = Yes/No;
• OR - odds ratio; CI - control interval; p-value - probability value; BMI - body mass index; WHO - World Health Organization; COPD - chronic obstructive pulmonary disease

Unadjusted analysis for PP showed significant effects of BMI (OR=5.8 for Overweight in relation to under or normal weight, and OR=7.4 for obese compared with under or normal weight; p=0.002), obesity (OR=3.4, p=0.002), coronary heart disease (OR=6.2, p<0.001), dyslipidemia (OR=2.8, p=0,002), diabetes mellitus (OR=6.0, p<0,001), heart stroke (OR=7.1, p<0,001), and number of morbidities (OR=3.1, p<0.001). After adjustment for confounding factors using multivariate logistic regression analysis and control for gender and age, PP was significantly associated with BMI (OR=6.5 and 5.7, p=0.014), coronary heart disease (OR=8.8, p<0.001), diabetes mellitus (OR=3.2, p=0.013), and number of comorbidities (OR=2.1, p=0.002) (Table 3).

Table 3
Summary of the logistic regression analysis results for Polypharmacy (PP). Niterói – RJ, Brazil, 2011/2012

	Unadjusted Regression			Adjusted Regression
	OR	CI(95%)	p-value	OR	CI(95%)	p-value
Gender (male/female)	1.57	[0.78; 3.16]	0.211	1.08	[0.43; 2.71]	0.874
Age (years)	0.98	[0.94; 1.02]	0.287	1,00	[0.94; 1.06]	0.969
BMI Classification (WHO)			0.002			0.014
Overweight/Under or Normal	5.76	[1.89; 17.54]	0.002	6.52	[1.81; 23.56]	0.004
Obese/Under or Normal	7.38	[2.38; 22.82]	0.001	5.72	[1.51; 21.60]	0.010
Obesity (Y/N)*	3.43	[1.54; 7.63]	0.002
Skin Color (non-white/white)	1.73	[0.90; 3.36]	0.103
Per capita family income	1.00	[0.99; 1.00]	0.233
Private Health Insurance (Y/N)*	1.51	[0.70; 3.24]	0.293
Marital Status (with/without partner)	0.83	[0.45; 1.56]	0.568
Current Smoking Status (Y/N)*	0.66	[0.35; 1.24]	0.195
COPD (Y/N)*	0.28	[0.04; 2.19]	0.223
Coronary Heart Disease (Y/N)*	6.22	[2.89; 13.41]	<0.001	8.80	[3.32; 23.33]	<0.001
Depression (Y/N)*	1.45	[0.69; 3.02]	0.326
Dyslipidemia (Y/N)*	2.83	[1.46; 5.48]	0.002
Diabetes (Y/N)*	6.01	[3.07; 11.77]	<0.001	3.15	[1.28; 7.77]	0.013
Heart Stroke (Y/N)*	7.12	[2.49; 20.35]	<0.001
Number of morbidities	3.06	[2.08; 4.50]	<0.001	2.14	[1.31; 3.49]	0.002

• ^*
  Y/N = Yes/No;
• OR was not calculated for polypharmacy and hypertension due to the absence of individuals with these conditions. OR - odds ratio; CI - control interval; p-value - probability value; BMI - body mass index; WHO - World Health Organization; COPD - chronic obstructive pulmonary disease

DISCUSSION

The present study aimed to evaluate the prevalence and factors associated with PP and PIM use in older adults enrolled in the Family Health Program in the municipality of Niterói, Brazil. The Family Health Program aims to assist a pre-designed part of the city and its population. In this way, the physicians that participate in the program follow their patients over time and can establish a relationship of care¹⁸.

A study conducted in Germany using a primary practice health insurance database showed a PP prevalence rate of 10%⁵, different from that found in this study (23.9%). However, the German study presented data collected from the national system, and it did not include all the medications the patients were actually using. Studies carried out with patients that used at least one medication, or not, found PP prevalence of rates of 47% in patients admitted to rheumatology and internal medicine departments at five hospitals in Norway¹⁹ and of 57% in geriatric patients (aged ≥75 years) in Sweden⁶. Other studies have reported PP prevalence rates significantly higher, as the Saudi Arabian study that investigated adult medical outpatients at a tertiary care center and observed a rate of 89%²⁰. This important difference between the prevalence rates described in the aforementioned surveys and that found in this study may be explained by the higher level of attention analyzed, since tertiary hospitals are associated with complicated diseases and multiple morbidity. All these studies used the same cutoff point to determine PP.

Studies performed with Intensive Care Unit populations show that older adults in long-term care present higher PP prevalence. On average, the number of medications used by the participants of this study was 3.2 drugs/person/day; meanwhile, other studies have reported numbers between 8²¹ and 5.6²². These lower rates may be explained by the continuous and close care provided by the Family Health Program, which enables a more careful treatment for the patients. However, it is worth mentioning that these rates can be underestimated, because only prescribed medication was considered, and self-medication is a common practice in Brazil. Furthermore, there is a lack of studies conducted in Primary Health Care, which hinders a more accurate comparison, since both aforementioned studies were carried out in tertiary health services.

In the present study, a PIM use prevalence rate of 24.8% was observed, 45.5% of the patients were also PP users (data not shown). Mo et al.²³ identified PIM use in 53.2% of patients according to the 2012 Beers criteria. In primary care, surveys conducted in Europe²⁴ and New Zeland²⁵ have observed PIM use prevalence rates of 44 and 42.7%, respectively. Another Brazilian study carried out with older adults in the municipality of Ribeirão Preto, state of Sao Paulo, found a PIM use prevalence rate of 59.2%¹³. This variability could be a result of the differences in drug availability in different locations, as well as in prescribing habits²⁵. In addition; some studies have only included individuals aged ≥75 years, which may explain the higher prevalence of PIM users. Another Brazilian study performed in São Paulo showed a higher PP prevalence rate (36%), which suggests that the single Family Health Program of Niterói may have a good impact in health assistance²⁶.

High PIM use prevalence was observed for the following drug classes: antihypertensives, antidepressants, vasodilators, digitalis and antiarrhythmics, which concurred with the findings by Farrell et al.¹², who found that the classes of drugs that ultimately emerged as priorities from the final rankings were associated with mental health, cardiovascular, gastroenterological, and neurological conditions. In this study, 87.8% of the patients were antihypertensive users, and 10.8% (21/195) of them were also PIM users. From those 21 PIM users, 20 were users of CCBs and PIM, and from the total 44 users of CCBs, 45.5% were PIM users. For instance, CCBs (specifically Nifedipine) should not be used in elderly patients because of their potential for hypotension and constipation. Some treatments, for a range of mental health and chronic diseases, often highlight drug classes with prolonged use have recently come into question (e.g., bisphosphonates, anticonvulsants, etc.). There are several drug classes for which a specialist may have initiated therapy, but a primary care practitioner needs to determine ongoing need (e.g., beta-blockers, antiplatelet agents, cholinesterase inhibitors), or symptomatic treatments in which ongoing benefit versus medication harm remains in doubt (e.g., urinary anticholinergics, opioids, serotonin reuptake inhibitors, typical antipsychotics). This broad range of drug classes suggests that overtreatment occurs throughout the full spectrum of Primary Health Care²⁰.

In this study, neither PIM use nor PP were significantly associated with gender or age, unlike what was found in another Brazilian study, in which the female gender was associated with PIM use¹². After adjusting gender and age, BMI, history of coronary heart disease, diabetes, and number of morbidities were directly associated with PP. All these chronic diseases are associated with multiple complications and often require treatment with multiple drugs, which can explain the higher number of drugs prescribed. In addition, there are behaviors that can contribute to the development and severity of the chronic aspect, such as alcoholism and smoking. Diabetes was especially identified as a risk factor, since it is commonly associated with noncompliance with nutritional guidelines, non-performance of daily glycemic controls, and unhealthy lifestyles²⁷. Moreover, a Brazilian study conducted in the state of Goiás that showed association between PP and eutrophic nutritional status, obesity, and use of diet, highlighted the need for nutritional surveillance and monitoring in the elderly population²⁸.

After multivariate logistic regression analysis, the main risk factor for PIM use was PP. It was found that PP increases by four times the chances of PIM use. These results show that while effective approaches to discontinuation exist, clinicians still clearly need assistance with negotiating changes with their patients, finding non-pharmacologic approaches to manage symptoms and managing the process of tapering. A Canadian study performed in Toronto²⁹ showed that in-home visits were the best way to correctly know the patient medication list, and thus avoid PP. Feedback to the primary physician and physician education on the promotion of rational prescribing³⁰ are also some successful strategies to reduce PP. According to Mukete³¹, fixed-dose combinations reduce the medication burden and, consequently, decrease PP, in addition to improving compliance. Furthermore, a study conducted in the Brazilian capital city, Brasília, that showed an increased frequency in the occurrence of clinically significant potential drug-drug interactions in dementia patients, reinforced the need for drug-drug interaction studies in specific elderly populations³².

Once there are no antidiabetic drugs in the Beers list, it is unexpected to find a relationship between diabetes mellitus and PIM use. However, diabetes mellitus is part of the metabolic syndrome that, according to WHO includes obesity, hypertension, diabetes mellitus, and dyslipidemia. All of these conditions are connected to each other and superpose their effects. Thus, patients do not usually have only diabetes, but also metabolic syndrome, and it is understandable how usually is related to PP. In addition, some of these conditions present the use of inappropriate drugs in their treatment, which explains the relationship between diabetes mellitus and PIM use.

This study presents several limitations. First, it is important to highlight that all its participants were Brazilian patients and professionals; therefore, the results obtained reflect social and economic conditions and singularities of the Brazilian health system. It is worth noting that, although the Brazilian health system is universal and egalitarian, the drugs offered by this system are still limited. Another limitation to this study regards its sample, which was mainly composed of older female adults (68.5%), increasing BMI levels and influencing the profile of most prevalent diseases found. It is also important to highlight that a qualitative definition to inappropriate medication was not used but, in practice, physicians have to consider the multiple variables involved in each case to decide if a certain drug should be used on a patient. An exclusive quantitative definition of PP was also used, which is another limitation to this study. A more complex definition refers to qualitative PP, which can be considered as the prescription, administration, and use of more drugs than needed for the patient, respecting the rationalization of pharmacology therapy. As in all cross-sectional studies, this survey did not consider temporality as a causal effect. It considered only prescribed medications at the time of interview, and it did not include self-medication and lost or forgotten prescriptions. This fact may underestimate the prevalence of PP and PIM use. Although the medications taken by the study participants were accurately recorded, medical comorbidities were not evaluated; which means that drugs to be avoided in certain diseases were not included in the prevalence of PIM use. It is important to emphasize that there is no Brazilian list for inappropriate medication for elderly people. Despite the fact that the Beers list is very commonly used worldwide, it is not complete for Brazilian outpatient clinic, which limited the evaluation intended in this study.

Prevalence rates of 23.9 and 24.8% were found for PP and PIM use, respectively. These rates are lower than those reported in another studies; however, the associations of PP with PIM use and of PP with BMI, history of coronary heart disease, diabetes, and number of morbidities show that these chronic and high prevalent diseases are associated with PIM use and PP. These results show the need to adequately monitor the prescriptions and train health professionals to identify risk groups and inappropriate medications in order to improve both adherence and affectivity of treatments and prescriptions security.

• How to cite: Constantino JL, Bozzi RP, Souza GPMM, Marchesi R, Jorge AJL, Correia DMS, et al. Polypharmacy, inappropriate medication use and associated factors among brazilian older adults. Cad Saúde Colet, 2020; Ahead of Print. https://doi.org/10.1590/1414-462X202028030245
• Study carried out at Departamento de Epidemiologia e Bioestatística, Instituto de Saúde Coletiva, Universidade Federal Fluminense (UFF) – Niterói (RJ), Brasil.
• Financial support: none.

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Publication Dates

• Publication in this collection
  03 Aug 2020
• Date of issue
  Jul-Set 2020

History

• Received
  03 Sept 2018
• Accepted
  17 Aug 2019