Patient safety in primary health care and polypharmacy: cross-sectional survey among patients with chronic diseases

Objective: to characterize and determine the polypharmacy prevalence in patients with chronic diseases and to identify the factors associated, in order to improvement of pharmaceutical care focused on patient safety. Methods: cross-sectional study included 558 patients, covered by primary health care, using a household and structured questionnaire. We analyzed the data on polypharmacy and its clinical and socioeconomic factors. Poisson regression analysis with robust variance was applied, with results expressed in prevalence ratio. Results: the results showed that polypharmacy (consumption of four or more drugs) was of 37.6%. The prevalence ratio analyses identified independent variables associated with polypharmacy: age (3.05), economic strata (0.33), way of medication acquisition through a combination of out-of-pocket and Brazilian public health system (1.44), diabetes and hypertension (2.11), comorbidities (coronary artery disease 2.26) and hospital admission (1.73). In the analyses, inappropriate medication use of the 278 patients (≥ 65 years) was associated with polypharmacy (prevalence ratio 4.04). Conclusion: polypharmacy study becomes an opportunity to guide the strategies for the patient safety to promote the medication without harm in chronic diseases.


Introduction
The World Health Organization (WHO), in 2017, has highlighted the polypharmacy as one of the key focus areas of its Third Global Patient Safety Challenge, Medication Without Harm. The term polypharmacy, which is the routine use of four or more medications, represents a main patient safety issue (1) . In this context, it is necesary a team-based care approach patient centered, such as strategy for clinical decision making, collaboration, adherence to prescribed regimen and monitoring. Team-based care includes the patient, the patient's primary care provider, and other professionals, such as cardiologists, nurses and pharmacists (2) . In primary health care (PHC) the risks to patients are much more related to the lack of monitoring during prolonged periods and the difficulties of access to health care. In the hospital setting, the patient safety is the comum practice, currently evolving towards primary care (3) .
Aditionally, the use of multiple drugs has been associated with an increased risk for potentially inappropriate medication (PIM). Studies have observed a relationship between polypharmacy and various factors including age and health status (4) .
Recognition of polypharmacy is the first step towards irracional use prevention (5) . However, it is necessary to know the possibilities of evaluating drug-related problems and increasing their safe and effective use. In this context, a systematic review on the use of PIM showed the impact of the intervention of pharmacists and the sensibilzation of physicians regarding the innappropriate prescription, contributing to the management of PHC to the patient (6) .
In Brazil, the pharmaceutical profession underwent important transformations, with a change of roles and focus on the provision of clinical services (7) . Regulatory advances defined the pharmacy as a health entity dedicated to providing a pharmaceutical service to promote better health care for patients (8) . In this reality, it is important to note that these services have gained momentum by implementing the models focused on patient-centered. In parallel, in 2017, new regulations were implemented in pharmaceutical education, covering three axes: Health Care, Technology and Innovation in Health and Health Management (9) . Important aspects of these implementations were reached in the field of pharmaceutical policies in PHC in the Brazilian Unified Health System (SUS) (10) . However, it imposes, in particular on the pharmacist, the need to advance in the qualification of the care offered to drugs users. In addition, the Ministry of Health establishes the National Patient Safety Program, and in 2017, within this Program established Safety Protocol in the prescription, use and administration of drugs (11) .
The objective of this study was to characterize and determine the prevalence of polypharmacy in patients with chronic diseases, and to identify the factors associated with it, in order to provide subsidies for the improvement of pharmaceutical care focused on patient safety in the PHC of the SUS. All the drugs were classified into pharmacological groups using the WHO Anatomical Therapeutic Chemical

Method
Classification System (ATC) (14) . Each participant's medication list, people aged 65 years or over, was evaluated for use of PIM by using the Beers' Criteria (15) .
All data were analyzes with the assistance of the

Results
In the ten primary care units, 558 patients aged 18 years or older participated in the observational study period.

Discussion
The main results of this study demonstrate of the prevalence of drug use, polypharmacy and PIM use in the PHC. The predominance was of drugs for the cardiovascular system, which may develop risks for adverse events due to polypharmacy (16) . In this situation, the drugs rational use by this group requires doses that meet their needs according to the international guidelines of medication without harm.
According to the Guideline for Prevention, Detection,

Evaluation and Management of Adult Hypertension, PHC
to the patient by pharmacists and others professionals should be share (2) . The importance of pharmaceutical services is recognized, that allowed patients with chronic conditions and polymedicated to have access to the pharmacotherapeutic follow up (7) . In this context, monitoring polypharmacy is a primary care practice that can contribute to reduce of side effects, as well as the risks of interactions, and improve adherence. This is important, because the polypharmacy has increased with greater life expectancy and as older people live with several chronic diseases (1) .
Referring to pharmaceutical care, the activities of clinical nature performed by pharmacists in Brazil are still incipient (17) . Futhermore, there are deficiencies in the workforce composition, which may affect the quality of the drug use and its results on health (18) . However, the pharmacists have expanded their roles and responsibilities in PHC through regulatory advancements.
During this study, diabetic and hypertensive users of PHC were prescribed with 3.3 drugs on average. Furthermore 37.6% of this population was exposed to polypharmacy. Several previous international studies have also reported the polypharmacy prevalence (19)(20) .
Among them, the results from a French study (20) were very similar to our own. In Brazil, the study carried out in the city of Ribeirão Preto in the SUS showed that the polypharmacy prevalence was 47.9% (19) .
The data of this study displayed association between the polypharmacy prevalence and the socioeconomic variables. Indeed, polypharmacy increased with aging, growing from 43% of polymedicated people at 60 years old to 89.4% for people aged over 61 years old. Previous population-based studies also found an association between polypharmacy and older age (19)(20) .
In addition, the economic status of the study population was also associated. Thus, in order to implement clinical pharmacists practice is essential the knowledge of the socio-economic characteristics of patients for reduce barriers to counseling in the therapeutic orientation.
Among the respondents who reported using drugs, 31.7% had all the drugs they need through the SUS. This result was consistent with several studies that have shown the low acquisition of medications by SUS (21)(22)(23) , especially for the treatment of hypertension and diabetes (24) . In addition, Diamantina is a microregion located in the Jequitinhonha Valley, with low population density and few studies on access and use of drugs. So, it is necessary to emphasize that the results corroborate with the findings of another study (25) , in which the highest proportions of www.eerp.usp.br/rlae 7 Araújo LU, Santos DF, Bodevan EC, Cruz HL, Souza J, Silva-Barcellos NM.
drug access were found in the more developed Brazilian regions, with a higher population density, observing and assessing the specificities of each region, especially in processes of regional planning of health actions.
Therefore, the access to drug by SUS combined with out-of-pocket (82.1%) is, consequently, associated with polypharmacy. In Brazil, there was high proportion of drug acess by purchase (26) , since 13% of patients reported not being able to buy something important to cover expenses with a health problems, and 41.8% of them pointed out the expense with drugs (27) .
In this context, this research carried out in a low-income region, such as Vale do Jequitinhonha, may support others works on access and the way of obtaining medicines. Whereas economic incentives and free provision by SUS of drugs may improve access and avoid high expenditures for drugs (28) .
Polypharmacy is a complex phenomenon, which helps distinguish a drug use for real health needs from not necessary use (29) . Therefore, it is necessary further research exploring their relationship with the SUS and health insurance. In Brazil, furthermore, economic crisis, health sector management and access to essential drug depend on how the drugs used were obtained (26) .
The expenses of the SUS with drugs grew, an important fact to be analyzed in a health system with polymedicated patients. Additionally, this issue is especially important for the country, since lower income families still proportionally commit more of their health care resources and drug spending has a significant share of these expenditures (27) .
This work explored the relationship between specific chronic diseases diagnosis and polypharmacy. Similar to previous Brazilian studies, high prevalence of chronic diseases, with hypertension and diabetes being the most common ones (19,30) . Multimorbidity is associated with a high number of prescribed medications (4) and suggests relatively rapid changes in prescription patterns.
Similar to the current findings, hospital admission was associated with polypharmacy (31) . It is important to emphasize that pharmacotherapeutic success throughout from the performance of the pharmacist from the continuity of care in the health system. In this sense, a new paradigm for pharmaceutical education, defending the teaching focused on clinical skills regarding patient safety (32) . In Brazil, these changes in professional priorities are reflected barriers and facilitators that were grouped: health system, local healthcare network, pharmacists, health team, clinical pharmacy services implementation process and external factors (33) .
The progression of diabetes and hypertension can progress to the development of comorbidities, and as a consequence, polypharmacy. In this sense, elderly patients with diabetes represent a population with a high incidence of comorbidities and a reduced ability to tolerate medication adverse effects and drug-drug interactions (34) .
The pharmacotherapy process in polymedicated patients involves understanding the drug related problems, and is necessary the identification of these problems associated with PIM in elderly patients.
As a consequence, Beers' Criteria address several important aspects of PIM use in older people. This study demonstrates that 41.0% of diabetic and hypertensive elderly patients, who are covered by primary care, using at least one PIM, as determined by this Criteria (15) and other studies have reported this use in Brazil (35)(36) .
The PIM use may have unintended consequences of its effects, although there is evidence about the risks and harmful impact from its use. In the analysis of PIM grouped by ATC system, it was observed the use was the group of drugs that act on the cardiovascular system (38.6%). This is not surprising, since Brazilian population study has identified this class of drugs as the most used by the elderly (35) . Additionally, in another observational study conducted in Spain (37) , the most frequent drugs were prescribed for the cardiovascular (16.9%), gastrointestinal (15.5%) and musculoskeletal system (15.3%) and for medication-related central nervous system treatments (10.8%).
Spironolactone was the most used drug (9.2%) by the patients studied that acts on the cardiovascular system, and should be avoided with variation in the level of kidney function, since its administration is associated with increased potassium, according to Beers' Criteria (15) . The use of nifedipine (immediate release) (7.4%) remains a concern because it is associated with hypotension and precipitating myocardial ischemia.  (36) and 95%CI 2.1-3.8; p<0.001 (38) . The results of this study show the need for continuous pharmacotherapeutic monitoring. The integrated care is receiving more attention, and there is good evidence of the benefit of pharmacist involvement in drugs management (5) .
Beers' Criteria is a clinical and public health tool to improve medication safety in older adults and to increase awareness of polypharmacy (15) . However, there may be cases in which the health care provider determines that a drug on the list is the only alternative. In this regard, there is the National List of Essential Medicines, used as a guideline for a rational prescription in PHC. However, to ensure the quality of primary care in the drug use it is necessary the use of the standardized list in order to contribute to the promotion of the quality of care (39) .
Besides that, measurement of safety events, e.g. the polypharmacy and PIM use, in the primary care setting is essential, and the appropriate use of polypharmacy would be the indicator of drugs safety on potentially inappropriate prescription.
Therefore measures that qualify health, prescription, and dispensing services are needed to promote the rational use of drugs, in the PHC, through drugs optimisation (39) .  (41) . The pharmacoepidemiology is an important tool for the pharmacist to develop indicators for the rational use of drugs. In sequence they conduct the This study may be limited by the regional differences in the polypharmacy prevalence that could be explained by professionals in primary care must ensure the quality of pharmacotherapy.
Our study, in addition to confirming polypharmacy in hypertensive and diabetic patients and the association of inappropriate use of medications, was essential to reflect on the pharmacist's role in the context of PHC.
In this sense, the study of polypharmacy becomes a key element, an opportunity for pharmacists in partnership with primary care professionals to develop guidelines for the pharmacotherapy of chronic diseases, especially hypertension and diabetes. As a consequence, obtain better health outcomes based on patient safety in PHC.