Marcus Vinicius Palmeira Oliveiraa; David Costa Buarquea,b
OBJECTIVE: In Brazil, 70% of older adults have at least one chronic disease and, of these, 60% use more than four medications regularly, characterizing polypharmacy. Potentially inappropriate medications (PIMs) are used by 40% of this population. Both polypharmacy and PIM use are associated with negative outcomes, such as increased frequency of drug interactions, falls, frailty, malnutrition, and in some cases, death.
METHOD: This was a cross-sectional study with retrospective data collection of all older patients admitted for clinical reasons to a tertiary care hospital in Brazil from March 2015 to February 2016. We evaluated patients for the presence of polypharmacy and PIM use, correlating these findings with other variables of interest.
RESULTS: The medical records of 456 patients were analyzed. Mean patient age was 83 years, and 71.3% were women. The mean Charlson comorbidity index (CCI) was 2.38, and dementia was the most prevalent comorbidity (36.6%). Polypharmacy was present in 56.5% of patients, and 46.4% of them used at least one PIM. Antipsychotics were the most frequently used PIM (46.2%), followed by benzodiazepines (33.0%). Drug interactions were detected in 53.5% of patients. The presence of polypharmacy was associated with the use of PIMs (p < 0.001). Additionally, both polypharmacy and PIM use were associated with drug interactions (p < 0.01), poorer functional status (p < 0.01), and higher CCI (p = 0.015).
CONCLUSION: In this study population, the prevalence of polypharmacy was 56.5%, and 46.5% of cases included the use of PIMs. Both conditions were associated with drug interactions, poorer functional status, and higher CCl.
Keywords: health of the elderly; inappropriate prescribing; polypharmacy
OBJETIVO: No Brasil, 70% dos idosos possuem ao menos uma patologia crônica e, destes, 60% usam mais de 4 medicamentos regularmente, constituindo a polifarmácia. Medicamentos potencialmente inapropriados (MPI) são utilizados por 40% dessa população. Tanto a polifarmácia quanto os MPI estão associados a desfechos negativos, como maior frequência de interação medicamentosa, quedas, fragilidade, desnutrição e, em alguns casos, mortalidade.
MÉTODO: Estudo transversal retrospectivo em que foram incluídos idosos internados por motivo clínico no hospital da Santa Casa de Misericórdia de Maceió (SCMM) entre março de 2015 e fevereiro de 2016. Foi avaliada a presença de polifarmácia e MPI, correlacionando-os com outras variáveis de 2 interesse.
RESULTADOS: Foram analisados 456 prontuários eletrônicos de pacientes com idade média de 83 anos, sendo 71,3% do sexo feminino. O índice de comorbidade de Charlson (ICC) médio foi de 2,38, sendo demência a morbidade mais prevalente (36,6%). Polifarmácia esteve presente em 56,5% dos pacientes e 46,4% tinham ao menos um MPI, sendo mais frequente o uso de antipsicóticos (46,2%), seguidos por benzodiazepínicos (33%). Interação medicamentosa foi detectada em 53,5% dos pacientes. A presença de polifarmácia se correlacionou com MPI (p < 0,001). Além disso, polifarmácia e MPI se correlacionaram com interação medicamentosa (p < 0,01), pior funcionalidade (p < 0,01) e maior ICC (p = 0,015).
CONCLUSÃO: Na população estudada, a presença de polifarmácia foi de 56,5% e a de MPI, 46,5%. Ambas se correlacionaram positivamente com a presença de interação medicamentosa, pior funcionalidade e maior ICC.
Palavras-chave: saúde do idoso; prescrição inadequada; polimedicação.
In recent decades, the phenomenon of population aging has become increasingly relevant, being accompanied by a rise in the prevalence of chronic diseases and functional limitations. Currently, one in nine persons in the world is aged 60 years or over, and this number is projected to increase to one in five by 2050.1 In Brazil, 70% of older adults have at least one chronic disease requiring regular pharmacological treatment, and 60% use more than four medications regularly,2 which represents, for most authors, the concept of polypharmacy.3,4
Pharmacological management is an essential component of geriatric care, and prescribing is the ultimate process of care that differentiates physicians. It is an extremely complex process, because it includes:
1. choosing the most appropriate drug;
2. determining the drug regimen to each patient;
3. monitoring the efficacy, and
4. adverse effects of each prescription.5
Potentially inappropriate medication (PIM) prescribing may cause preventable adverse drug events, with serious consequences for patients. It is defined as the prescription that introduces a significant risk of an adverse drug-related event when there is evidence for an equally or more effective alternative medication.6,7 Older adults are more susceptible to these events, and any new symptom should be considered drug related until proven otherwise.8 In addition, the use of PIMs is associated with increased risk of hospitalization and death, making this a significant health problem for the elderly population.7
Another major challenge is that most trials of new drugs exclude older adults; therefore, the doses approved for use in young adults may not be suitable for use in older age groups. In addition, age-related physiological changes as well as sensory and cognitive changes (more common in older patients) are associated with changes in pharmacokinetics and pharmacodynamics, hindering proper medication management.5,8,9
In view of this problem, specialist groups began to investigate the harmful effects of drugs in the elderly, and the most widely used criteria for PIMs are the Beers criteria,10 Screening Tool of Older Person’s Prescriptions (STOPP),11 Screening Tool to Alert Doctors to Right Treatment (START),12 and Fit for the Aged (FORTA).13 Among them, we highlight the American Geriatrics Society 2015 Beers Criteria Update Expert Panel,10 which developed a list of PIMs best avoided in older adults considering the level of evidence and strength of recommendation for the use of each drug. However, despite the increasing concern about drug prescriptions, especially PIM prescribing, and a more specialized view of the elderly, new active principles are investigated daily, making medication management increasingly complex in this age group, resulting in an increased iatrogenic risk.
The objective of this study was to evaluate the prevalence of PIM use and polypharmacy among aged inpatients and correlate it to the variables of interest in order to determine general characteristics associated with these conditions.
This was a cross-sectional study with retrospective data collection of all older patients (≥ 60 years of age) admitted for clinical reasons to a tertiary care hospital, Santa Casa de Misericórdia de Maceió, northeastern Brazil, from March 2015 to February 2016. Exclusion criteria were readmission during the study period and medical records with missing data for the variables of interest. The study was approved by the Research Ethics Committee of Universidade Estadual de Ciências da Saúde de Alagoas (UNCISAL) (registration number: CAAE 56764616.5.0000.5011/project number: 1.685.590).
The electronic medical records of all eligible patients were retrospectively reviewed, and data were collected using a standardized form. The following variables were analyzed: age (in completed years); length of hospital stay (in days); functional status (level of dependence in activities of daily living [ADL]); the Charlson comorbidity index (CCI)14 (predictor of 1-year prognosis and mortality); number of medications; presence of polypharmacy7 (five or more medications); presence of PIMs (using the Beers criteria); and presence of drug interactions (using the Drug Interaction Checker database of the Medscape App for Android, Copyright 2015 by WebMD LLC).
Data were tabulated in the Google Docs platform and then analyzed using SPSS, version 16.0. Data were examined for the presence or absence of PIMs and the presence or absence of polypharmacy and compared with the variables of interest. Statistical analyses were performed using the chi-square test or Student’s t test, depending on the variable tested, at a significance level of p < 0.05.
Of 606 patients’ medical records reviewed for eligibility, 150 were excluded (123 readmissions and 27 with missing data). Therefore, 456 patients were included in the analysis. Mean patient age was 83 (± 8.24) years, and 71.3% were women. Most patients (62.3%) had some functional dependence, and 27.4% were totally dependent for ADLs. Mean length of hospital stay was 20 days (median, 13 days), and most patients (31.6%) remained hospitalized for 7 to 14 days (Table 1).
Regarding patient severity, the mean CCI was 2.38; 41.4% had a CCI between 1 and 2, corresponding to a mortality rate of 26.0% in 1 year. The most common comorbidities were dementia (36.6%), diabetes with target organ damage (29.8%), and cerebrovascular disease (20.0%) (Table 1).
The prevalence of polypharmacy was 56.5%. The number of medications used ranged from 0 to 17 on admission, with a mean of 5.69 and a median of 5 medications per patient (Table 2).
Of the total sample, 46.5% used at least one PIM on hospital admission, 11.6% used two PIMs, and 4.6% used three or more PIMs. The most commonly used PIM class was antipsychotics (46.2%). For 53.5% of patients, the outpatient prescriptions showed some drug interaction (Table 2), increasing proportionally to the number of medications used.
Patients using PIMs regularly did not differ in sex or age. The use of PIMs was associated with higher rates of ADL dependence, presence of polypharmacy, and drug interactions as well as with a higher CCI (Table3). Similarly, the presence of polypharmacy was also associated with poorer functional status, higher CCI, PIM use, and drug interactions (Table 4).
The results showed a high prevalence of polypharmacy and PIM use in the study sample, highlighting the susceptibility of older adults to these conditions. Our sample included only hospitalized older patients, a more compromised population with increased mean age and comorbidities (41% had a CCI ≥ 3), which may explain the high levels of functional limitations found in our patients, as well as a longer mean hospital stay, which is in agreement with data from the literature.15
Of the total sample, 56.5% of patients used at least five medications and 14.4% were chronic users of 10 or more medications (hyperpolypharmacy). In addition to the prevalence of polypharmacy, the mean number of medications used by our patients was similar to that of other studies worldwide. In the United States, about 60% of older adults use polypharmacy and 20%, hyperpolypharmacy.16 Mizokami et al.17 reported the use of a mean of 4.9 medications per hospitalized older patient. Hubbard et al.18 evaluated 1216 older patients admitted to 11 Australian hospitals and found that, on admission, 23.8% of patients were using hyperpolypharmacy, which was associated with presence of pain, dyspnea, and functional decline during hospitalization. In the study conducted by Rosted et al.,19 polypharmacy was present in 62% and hyperpolypharmacy in 20% of older patients admitted to a tertiary care hospital, with a direct association with the presence of frailty and a 5-fold higher risk of readmission within 14 days than in patients using up to four medications. In the study by Nobili et al.,20 with a similar methodology, the prevalence of polypharmacy was 51.9% in 1332 older patients admitted to an Italian hospital. In the ambulatory setting, Qato et al.21 analyzed 2976 patients in the United States and found that 73% of older adults used five or more medications daily.
Although the literature emphasizes that polypharmacy leads to negative outcomes for older adults, the mean number of medications used by both hospitalized and community-dwelling older persons is still quite high all over the world. This is possibly due to the increased prevalence of chronic degenerative diseases associated with aging, hindering the use of non-pharmacological treatment alone or discontinuation of essential drugs. Therefore, physicians should be alert to this problem and prescribe only medications with proven benefit, based on the best available evidence.20
The prevalence of PIM use was also high, with antipsychotics as the leading drug class for PIM prescribing, which is consistent with data from the literature.22,23 Martins et al.,24 in a study of 621 older adults living in Viçosa, a city in the state of Minas Gerais, Brazil, found a prevalence of 43.8% for PIM use. In a study of 667 older patients admitted to a university hospital in the United States, Bahat et al.22 found a PIM prevalence of 40%, and the most common PIM-related drugs were antipsychotics, followed by vitamin supplements, aspirin, and anticholinergics. In a systematic review of 778 articles using the main criteria available for identification of PIMs (Beers, STOPP, and START), benzodiazepines, nonsteroidal anti-inflammatory drugs (NSAIDs), antipsychotics and antihistamines were the most common drugs reported as potentially inappropriate for older persons.23
In the present study, PIM use was significantly associated with poorer functional status, polypharmacy, and presence of dementia (p < 0.001), with no difference between men and women. As for benzodiazepine use, there was a statistical association with the presence of polypharmacy (p = 0.04), with these drugs being more commonly prescribed in this condition. These results are similar to those reported by Vidal et al.,25 who found the same associations described here, except for an association of female gender with an increased risk for the use of psychotropics among aged inpatients.
The predominant use of psychotropics may be explained by the large number of patients with dementia and, consequently, behavioral and neuropsychiatric symptoms. The benefits of controlling these symptoms may outweigh the risks of using these medications, although such practice is not supported by research evidence. Although benzodiazepines are associated with an increased risk of falls and cognitive impairment, they are among the most commonly prescribed PIMs,23,25-27 as well as N SAIDs,23,26 which are associated with gastric, cardiovascular and renal impairment, indicating a worrisome practice due to increased iatrogenic risk.
Despite the finding that older patients who used PIMs had poorer functional status (p < 0.01), we could not define a cause-consequence relationship,23,25 mainly because of the methodological limitations of the study. The presence of multiple comorbidities22 is associated as a risk factor for PIM use in the literature, which was also observed in the present study, where patients using PIMs had a higher CCI (2.62; p = 0.015). Dementia was the only comorbidity that, alone, was statistically associated with PIM use in the present study (p = 0.01), probably because of the strong association of this condition with antipsychotic use. Previous studies have also shown an association with polypharmacy and increased risk of drug interactions.8 Diabetes28 and chronic kidney disease26 have also been associated with PIM use, although this was not a finding of the present study.
As observed in previous studies,24,22 the number of PIMs was higher in patients using polypharmacy (p < 0.01) and vice versa. This is probably due to the fact that the greater the number of medications used, the greater the likelihood of PIM use, as shown in the study conducted by Weng et al.,29 who found that patients prescribed five or more drugs had a 5.4-fold higher PIM risk than those prescribed two or fewer drugs. Another significant finding was the higher rate of drug interactions among patients who used at least one PIM (p < 0.001), which is consistent with data from the literature.8,30
Given the methodological (observational and cross-sectional) limitations of this study, it was not possible to establish objective risks associated with the conditions under study in some of the variables of interest. However, a trend toward significance can be observed in the present findings in view of the similarity of these results with those of several published studies.
In this study population, the prevalence of polypharmacy was 56.5%, and 46.5% of cases included the use of PIMs. Both conditions were associated with drug interactions, poorer functional status, and higher CCI. The most common PIM-related drugs were antipsychotics and benzodiazepines. Therefore, it is extremely important that the health care team monitor the use of polypharmacy and PIMs in older patients, especially those meeting the characteristics reported in this study, in order to minimize iatrogenic risks.
CONFLICT OF INTERESTS
The authors declare no conflict of interests.
1. United Nations Population Fund, HelpAge International. Ageing in the Twenty-First Century: A Celebration and A Challenge. Executive summary. Nova York/Londres; 2012.
2. Ramos LR, Tavares NU, Bertoldi AD, Farias MR, Oliveira MA, Luiza VL, et al. Polypharmacy and Polymorbidity in Older Adults in Brazil: a public health challenge. Rev Saúde Pública. 2016 Dec;50(Suppl 2):9s. DOI: 10.1590/S1518-8787.2016050006145
3. Gnjidic D, Hilmer SN, Blyth FM, Naganathan V, Waite L, Seibel MJ, et al. Polypharmacy cutoff and outcomes: five or more medicines were used to identify community-dwelling older men at risk of different adverse outcomes. J Clin Epidemiol. 2012;65:989-95. https://doi.org/10.1016/j.jclinepi.2012.02.018
4. Lu WH, Wen YW, Chen LK, Hsiao FY. Effect of polypharmacy, potentially inappropriate medications and anticholinergic burden on clinical outcomes: a retrospective cohort study. CMAJ. 2015;187:E130-7. https://doi.org/10.1503/cmaj.141219
5. Milton JC, Hill-Smith I, Jackson SHD. Prescribing for older people. BMJ. 2008 Mar;336(7644):606-9. https://doi.org/10.1136/bmj.39503.424653.80
6. Opondo D, Eslami S, Visscher S, Rooij SE, Verheij R, Korevaar JC, et al. Inappropriateness of medication prescriptions to elderly patients in the primary care setting: a systematic review. PLoS One. 2012;7(8):e43617. https://doi.org/10.1371/journal.pone.0043617
7. Oliveira MA, Amorim WW, Oliveira CRB, Coqueiro HL, Gusmao LC, Passos LC. Consenso brasileiro de medicamentos potencialmente inapropriados para idosos. Geriatr Gerontol Aging. 2016;10(4):168-81. DOI: 10.5327/Z2447-211520161600054
8. Ferreira F, Diniz JSV, Medeiros-Souza P, Freitas MPD, Camargos EF, Kusano LTE, et al. Potential drug interactions among elderly with dementia. Geriatr Gerontol Aging. 2015;9(1):21-5.
9. Parsons C. Polypharmacy and inappropriate medication use in patients with dementia: an underresearched problem. Ther Adv Drug Saf. 2017 Jan;8(1):31-46. DOI: 10.1177/2042098616670798
10. By the American Geriatrics Society 2015 Beers Criteria Update Expert Panel. American Geriatrics Society 2015 Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. J Am Geriatr Soc. 2015;63:2227-46. https://doi.org/10.1111/jgs.13702
11. Hamilton H, Gallagher P, Ryan C, Byrne S, O'Mahony D. Potentially inappropriate medications defined by STOPP criteria and the risk of adverse drug events in older hospitalized patients. Arch Intern Med. 2011;171:1013-9. https://doi.org/10.1001/archinternmed.2011.215
12. Gallagher P, Ryan C, Byrne S, Kennedy J, O'Mahony D. STOPP (Screening Tool of Older Person's Prescriptions) and START (Screening Tool to Alert doctors to Right Treatment). Consensus validation. Int J Clin Pharmacol Ther. 2008;46:72-83.
13. Kuhn-Thiel AM, WeiB C, Wehling M, FORTA authors/expert panel members. Consensus validation of the FORTA (Fit For The Aged) List: a clinical tool for increasing the appropriateness of pharmacotherapy in the elderly. Drugs Aging. 2014;31(2):131-40. https://doi.org/10.1007/s40266-013-0146-0
14. Charlson ME, Szatrowski TP, Peterson J, Gold J. Validation of a combined comorbidity index. J Clin Epidemiol. 1994;47:1245-51.
15. Beard JR, Officer A, de Carvalho IA, Sadana R, Pot AM, Michel JP, et al. The World report on ageing and health: a policy framework for healthy ageing. The Lancet. 2016;387(10033):2145-54. https://doi.org/10.1016/S0140-6736(15)00516-4
16. Rocchiccioli JT, Sanford J, Caplinger B. Polymedicine and aging. Enhancing older adult care through advanced practitioners. GNPs and elder care pharmacists can help provide optimal pharmaceutical care. J Gerontol Nurs. 2007 Jul;33(7):19-24.
17. Mizokami F, Koide Y, Noro T, Furuta K. Polypharmacy with common diseases in hospitalized elderly patients. Am J Geriatr Pharmacother. 2012 Apr;10(2):123-8. DOI: 10.1016/j.amjopharm.2012.02.003
18. Hubbard RE, Peel NM, Scott IA, Martin JH, Smith A, Pillans PI, et al. Polypharmacy among inpatients aged 70 years or older in Australia. Med J Aust. 2015 Apr 20;202(7):373-7. DOI: 10.5694/mja13.00172
19. Rosted E, Schultz M, Sanders S. Frailty and polypharmacy in elderly patients are associated with a high readmission risk. Dan Med J. 2016 Sep;63(9). pii: A5274.
20. Nobili A, Licata G, Salerno F, Pasina L, Tettamanti M, Franchi C, et al. Polypharmacy, length of hospital stay, and in-hospital mortality among elderly patients in internal medicine wards. The REPOSI study. Eur J Clin Pharmacol. 2011 May;67(5):507-19. DOI: 10.1007/s00228-010-0977-0
21. Qato DM, Alexander GC, Conti RM, Johnson M, Schumm P, Lindau ST. Use of prescription and over-the-counter medications and dietary supplements among older adults in the United States. JAMA. 2008 Dec 24;300(24):2867-78. DOI: 10.1001/jama.2008.892
22. Bahat G, Bay I, Tufan A, Tufan F, Kilic C, Karan MA. Prevalence of potentially inappropriate prescribing among older adults: A comparison of the Beers 2012 and Screening Tool of Older Person's Prescriptions criteria version 2. Geriatr Gerontol Int. 2017 Sep;17(9):1245-51. DOI: 10.1111/ggi.12850
23. Lucchetti G, Lucchetti AL. Inappropriate prescribing in older persons: A systematic review of medications available in different criteria. Arch Gerontol Geriatr. 2017;68:55-61. DOI: 10.1016/j.archger.2016.09.003
24. Martins GA, Acurcio FA, Franceschini S do C, Priore SE, Ribeiro AQ. Use of potentially inappropriate medications in the elderly in Viçosa, Minas Gerais State, Brazil: a population-based survey. Cad Saúde Pública. 2015 Nov;31(11):2401-12. DOI: 10.1590/0102-311X00128214
25. Vidal X, Agustí A, Vallano A, Formiga F, Moyano AF, García J, et al. Elderly patients treated with psychotropic medicines admitted to hospital: associated characteristics and inappropriate use. Eur J Clin Pharmacol. 2016 Jun;72(6):755-64. DOI: 10.1007/s00228-016-2032-2
26. Cojutti P, Arnoldo L, Cattani G, Brusaferro S, Pea F. Polytherapy and the risk of potentially inappropriate prescriptions (PIPs) among elderly and very elderly patients in three different settings (hospital, community, long-term care facilities) of the Friuli Venezia Giulia region, Italy: are the very elderly at higher risk of PIPs? Pharmacoepidemiol Drug Saf 2016 Sep;25(9):1070-8. DOI: 10.1002/pds.4026
27. Morgan SG, Weymann D, Pratt B2, Smolina K, Gladstone EJ, Raymond C, et al. Sex differences in the risk of receiving potentially inappropriate prescriptions among older adults. Age Ageing. 2016 Jul;45(4):535-42. DOI: 10.1093/ageing/afw074
28. Formiga F, Vidal X, Agustí A, Chivite D, Rosón B, Barbé J, et al. Inappropriate prescribing in elderly people with diabetes admitted to hospital. Diabet Med. 2016 May;33(5):655-62. DOI: 10.1111/dme.12894
29. Weng MC, Tsai CF, Sheu KL, Lee YT, Lee HC, Tzeng SL, et al. The impact of number of drugs prescribed on the risk of potentially inappropriate medication among outpatient older adults with chronic diseases. QJM. 2013 Nov;106(11):1009-15. https://doi.org/10.1093/qjmed/hct141
30. Alkan A, Yajar A, Karci E, Koksoy EB2, Ürün M, Jenler FÇ, et al. Severe drug interactions and potentially inappropriate medication usage in elderly cancer patients. Support Care Cancer. 2017 Jan;25(1):229-36. https://doi.org/10.1007/s00520-016-3409-6
January 22 2018.
Accepted em March 13 2018.