Acessibilidade / Reportar erro

Prevalence of pharmacological adherence in patients with coronary artery disease and associated factors* * Paper extracted from master’s thesis “Fatores que interferem na adesão farmacológica em pacientes com doença arterial coronariana”, presented to Universidade Federal de São Paulo, Escola Paulista de Enfermagem, São Paulo, SP, Brazil. This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) – Finance Code 001, Brazil.

Abstracts

Objective:

to assess the prevalence of pharmacological adherence in patients with coronary artery disease and to identify factors associated with adherence.

Method:

a crosssectional, correlational study, including 198 patients with a previous diagnosis of coronary artery disease. Pharmacological adherence was assessed by the four-item Morisky Green test, and the factors that potentially interfere with adherence were considered independent variables. The association between the variables was determined by the Cox model, with a 5% significance level.

Results:

43% of the patients adhered to the treatment. Fatigue and palpitation, never having consumed alcohol and being served by medical insurance were associated with adherence. Lack of adherence was associated with considering the treatment complex, consumption of alcohol and being served by the public health care system. In the multiple analysis, the patients with fatigue and palpitations had a prevalence of adherence around three times higher and alcohol consumption was associated with a 2.88 times greater chance of non-adherence.

Conclusion:

more than half of the patients were classified as non-adherent. Interventions can be directed to some factors associated with lack of adherence.

Descriptors:
Coronary Artery Disease; Medication Adherence; Nursing; Health Education; Treatment Adherence and Compliance; Patient Compliance


Objetivo:

avaliar a prevalência da adesão farmacológica de pacientes com doença arterial coronariana e identificar os fatores associados à adesão.

Método:

estudo transversal, correlacional, incluindo 198 pacientes com diagnóstico prévio de doença arterial coronariana. A adesão farmacológica foi avaliada pelo teste de Morisky Green de quatro itens e os fatores que potencialmente interferem na adesão foram considerados variáveis independentes. A associação entre as variáveis foi verificada pelo modelo de Cox, com nível de significância de 5%.

Resultados:

43% dos pacientes aderiram ao tratamento. Associaram-se à adesão os sintomas de fadiga e palpitação, nunca ter ingerido bebida alcoólica e ser atendido por convênio médico. Associaram-se à falta de adesão considerar o tratamento complexo, o consumo de bebidas alcoólicas e ser atendido pelo sistema público de saúde. Na análise múltipla, os pacientes que apresentavam fadiga e palpitação tiveram prevalência de adesão em torno de três vezes maior e o consumo de álcool associou-se a uma chance 2,88 vezes maior de não adesão.

Conclusão:

mais da metade dos pacientes foram classificados como não aderentes. Intervenções podem ser direcionadas para alguns fatores associados à falta de adesão.

Descritores:
Doença da Artéria Coronariana; Adesão à; Medicação; Enfermagem; Educação em Saúde; Cooperação e Adesão ao Tratamento; Cooperação do Paciente


Objetivo:

evaluar la prevalencia de la adhesión farmacológica de pacientes con enfermedad arterial coronaria e identificar los factores asociados a la adhesión.

Método:

estudio transversal, correlacional, que incluyó a 198 pacientes con diagnóstico previo de enfermedad arterial coronaria. Se evaluó la adhesión farmacológica mediante la prueba de Morisky Green de cuatro ítems y se consideró como variables independientes los factores que potencialmente interfieren en la adhesión. La asociación entre las variables se verificó con el modelo de regresión de Cox, con nivel de significancia del 5%.

Resultados:

el 43% de los pacientes adherían al tratamiento. Se asociaron a la adhesión los síntomas de fatiga y palpitaciones, nunca haber ingerido bebida alcohólica y recibir tratamiento de medicina prepaga. Se asoció a la falta de adhesión considerar complejo el tratamiento, consumir bebidas alcohólicas y recibir tratamiento del sistema público de salud. En el análisis múltiple, los pacientes que presentaban fatiga y palpitaciones tuvieron cerca de tres veces más prevalencia de adhesión y el consumo de alcohol se asoció a una posibilidad 2,88 veces mayor de no adhesión.

Conclusión:

se clasificó a más de la mitad de los pacientes como no adherentes. Es posible direccionar acciones hacia algunos factores asociados a la falta de adhesión.

Descriptores:
Enfermedad de la Arteria Coronária; Cumplimiento de la Medicación; Enfermería; Educación en Salud; Cumplimiento y Adherencia al Tratamiento; Cooperación del Paciente


Introduction

According to the American Heart Association (AHA)(11 Virani SS, Alonso A, Benjamin EJ, Bittencourt MS, Callaway CW, Carson AP, et al. Heart Disease and Stroke Statistics-2020 Update: A Report From the American Heart Association. Circulation. 2020;141(9):e139-e596. doi:10.1161/CIR.0000000000000757
https://doi.org/10.1161/CIR.000000000000...
), 18.2 million 20-year-old or older Americans had coronary artery disease (CAD) between 2013 and 2016. In 2020, it was estimated that 720,000 Americans had some coronary event, including hospitalization for acute myocardial infarction (AMI) or death due to CAD. In Brazil, 242,858 hospitalizations occurred in 2019 due to ischemic heart disease. These data have a direct impact on economy and society(22 Ministério da Saúde (BR), Datasus. Sistema de Informações Hospitalares do SUS - SIH/SUS. [Internet]. [Acesso 20 jun 2020]. Disponível em: http://tabnet.datasus.gov.br/cgi/tabcgi.exe?idb2012/d29.def = 2
http://tabnet.datasus.gov.br/cgi/tabcgi....
).

The treatment of CAD includes continuous use of medications, such as antihypertensives, antiplatelet agents, anticoagulants and statins. Invasive treatments can also be implemented, including coronary artery bypass grafting or percutaneous coronary intervention, in addition to the implementation of non-pharmacological measures, represented by incorporating a healthy lifestyle(33 Knuuti J, Wijns W, Saraste A, Capodanno D, Barbato E, Funck-Brentano C, et al. 2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes. Eur Heart J. 2020;41(3):407-77. doi: 10.1093/eurheartj/ ehz425
https://doi.org/10.1093/eurheartj/ehz425...

4 Thygesen K, Alpert JS, Jaffe AS, Chaitman BR, Bax JJ, Morrow DA, et al. Fourth Universal Definition of Myocardial Infarction. J Am Coll Cardiol. 2018;72(18):2231-64. doi: 10.1016/j.jacc.2018.08.1038
https://doi.org/10.1016/j.jacc.2018.08.1...
-55 Arnett DK, Blumenthal RS, Albert MA, Buroker AB, Goldberger ZD, Hahn EJ, et al. 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease: A Report of the American College of Cardiology American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019;10;140(11):e596-e646. doi: 10.1161/ CIR.0000000000000678
https://doi.org/10.1161/CIR.000000000000...
).

Adherence to pharmacological and nonpharmacological treatment plays a crucial role in achieving satisfactory clinical outcomes in patients with CAD, including preventing ischemia, reducing symptoms, improving quality of life, decreasing readmissions and morbidity and mortality due to cardiovascular diseases(55 Arnett DK, Blumenthal RS, Albert MA, Buroker AB, Goldberger ZD, Hahn EJ, et al. 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease: A Report of the American College of Cardiology American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019;10;140(11):e596-e646. doi: 10.1161/ CIR.0000000000000678
https://doi.org/10.1161/CIR.000000000000...
). The World Health Organization (WHO) defines adherence as the extent to which a person’s behaviour – taking medication, following a diet, and/or executing lifestyle changes, corresponds with agreed recommendations from a health care provider. There are five dimensions that interfere with this adherence: related to the patient, to the disease, the treatment, to the health care system and team, and to the socioeconomic factors(66 World Health Organization (WHO). Adherence to longterm therapies: evidence for action. [Internet]. Geneva: WHO; 2003 [cited Jun 18, 2017]. Available from: https:// www.who.int/chp/knowledge/publications/adherence_report/en/
www.who.int/chp/knowledge/publications/a...
).

In developed countries, only 50% of the patients with chronic diseases continue their treatment, including pharmacological and non-pharmacological measures. In developing countries, such as Brazil, this number has varied from 51% to 56.5%(66 World Health Organization (WHO). Adherence to longterm therapies: evidence for action. [Internet]. Geneva: WHO; 2003 [cited Jun 18, 2017]. Available from: https:// www.who.int/chp/knowledge/publications/adherence_report/en/
www.who.int/chp/knowledge/publications/a...

7 Birck MG, Goulart AC, Lotufo PA, Bensenor IM. Secondary prevention of coronary heart disease: a cross-sectional analysis on the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Sao Paulo Med. J. 2019;137(3):223-33. doi: https://doi.org/10.1590/1516-3180.2018.0531140319
https://doi.org/10.1590/1516-3180.2018.0...
-88 Santos VB, Silva LL, Guizilini S, Valente IB, Barbosa CB, Carneiro TAB, et al. Adherence to antiplatelet and statin therapy by patients with Acute Coronary Syndrome following discharge. Enferm Clin. 2020;pii:S1130-8621(20)30237-0. doi: 10.1016/j.enfcli.2020.02.020
https://doi.org/10.1016/j.enfcli.2020.02...
) when considering only pharmacological adherence. Thus, in order to contribute to the primary and secondary prevention of CAD, the multidisciplinary team must identify the factors that interfere with adherence to treatment, in order to implement interventions that may minimize these barriers(55 Arnett DK, Blumenthal RS, Albert MA, Buroker AB, Goldberger ZD, Hahn EJ, et al. 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease: A Report of the American College of Cardiology American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019;10;140(11):e596-e646. doi: 10.1161/ CIR.0000000000000678
https://doi.org/10.1161/CIR.000000000000...
).

A Brazilian study identified that only 26% of the hospitalized patients with CAD adhere to the pharmacological treatment(99 Sobral PD, Gomes ED, Carvalho PO, Godoi ET, Oliveira DC. Prevalência de adesão medicamentosa em pacientes com doença arterial coronariana crônica. Enferm Brasil 2020;19(2):98-104. doi: https://doi.org/10.33233/eb.v19i2.2137
https://doi.org/10.33233/eb.v19i2.2137...
). Another study found that 49.3% of the patients had low adherence to statins and antiplatelet agents or potential for such 30 days after hospital discharge for Acute Coronary Syndrome(88 Santos VB, Silva LL, Guizilini S, Valente IB, Barbosa CB, Carneiro TAB, et al. Adherence to antiplatelet and statin therapy by patients with Acute Coronary Syndrome following discharge. Enferm Clin. 2020;pii:S1130-8621(20)30237-0. doi: 10.1016/j.enfcli.2020.02.020
https://doi.org/10.1016/j.enfcli.2020.02...
). Lack of adherence to pharmacological treatment is a complicating factor for readmissions(1010 Wu Q, Zhang D, Zhao Q, Liu L, He Z, Chen Y, et al. Effects of transitional health management on adherence and prognosis in elderly patients with acute myocardial infarction in percutaneous coronary intervention: a cluster randomized controlled trial. PLoS One. 2019;14(5):e0217535. doi:10.1371/journal.pone.0217535
https://doi.org/10.1371/journal.pone.021...
) due to decompensations. A meta-analysis including 10 studies with 106,002 patients demonstrated that adequate pharmacological adherence reduced the risk of global and cardiovascular mortality, in addition to hospitalization for cardiovascular disease and AMI(1111 Du L, Cheng Z, Zhang Y, Li Y, Mei D. The impact of medication adherence on clinical outcomes of coronary artery disease: A meta-analysis. Eur J Prev Cardiol. 2017;24(9):962-70. doi: 10.1177/2047487317695628
https://doi.org/10.1177/2047487317695628...
).

Therefore, during the delivery of nursing care for inpatients or outpatients, nurses must assess the factors associated with pharmacological non-adherence, so that nursing interventions can be established individually and focused on these variables. To the best of the authors’ knowledge, only three Brazilian studies that evaluated the factors associated with pharmacological non-adherence in patients with CAD were identified(77 Birck MG, Goulart AC, Lotufo PA, Bensenor IM. Secondary prevention of coronary heart disease: a cross-sectional analysis on the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Sao Paulo Med. J. 2019;137(3):223-33. doi: https://doi.org/10.1590/1516-3180.2018.0531140319
https://doi.org/10.1590/1516-3180.2018.0...
,99 Sobral PD, Gomes ED, Carvalho PO, Godoi ET, Oliveira DC. Prevalência de adesão medicamentosa em pacientes com doença arterial coronariana crônica. Enferm Brasil 2020;19(2):98-104. doi: https://doi.org/10.33233/eb.v19i2.2137
https://doi.org/10.33233/eb.v19i2.2137...
,1212 Sobral PD, Oliveira DC, Gomes ET, Carvalho PO, Brito NMT, Oliveira AGC, et al. Reasons for medication noncompliance in patients with coronary artery disease. Rev Soc Bras Clin Med. [Internet]. 2017 [cited Jul 13, 2020];15(3):166-70. Available from: http://www.sbcm.org.br/ojs3/index.php/rsbcm/article/view/288/263
http://www.sbcm.org.br/ojs3/index.php/rs...
). Thus, new studies are needed, with population samples from different locations and addressing other possible non-adherence factors. This study aimed to assess the prevalence of pharmacological adherence in patients with CAD and to identify factors associated with adherence.

Method

A cross-sectional, correlational study, based on the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines for crosssectional studies. It was developed in a hospital that is a reference in Cardiology in the city of São Paulo (SP), with data collection performed from November 2017 to January 2018 in the Hospitalization Units (566 beds), in the Intensive Care Units (646 beds) and in the Hemodynamics sector (51 beds).

Eligible patients were those hospitalized with a medical diagnosis of CAD, aged over 18 years. The exclusion criteria were chest pain, dyspnea or symptomatic hypotension during data collection, because these symptoms would make it impossible to interview the patients.

The sample size was calculated(1313 Chow SC, Wang H, Shao J. Sample size calculations in clinical research. Boca Raton: CRC Press; 2007.) using the R 3.4.1 software, based on data from a previous study, which identified adequate pharmacological adherence in 56.5%(77 Birck MG, Goulart AC, Lotufo PA, Bensenor IM. Secondary prevention of coronary heart disease: a cross-sectional analysis on the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Sao Paulo Med. J. 2019;137(3):223-33. doi: https://doi.org/10.1590/1516-3180.2018.0531140319
https://doi.org/10.1590/1516-3180.2018.0...
) of the patients with CAD. Considering an 80% power and a 10% accuracy, a minimum sample size of 198 patients was obtained.

Patients were selected by one of the authors of the study, a nurse specialized in Cardiology and Hemodynamics, who daily analyzed the patients’ medical records in the selected units and identified those who met the eligibility criteria. The nurse explained the objectives of the study and invited them to participate, by offering the free and informed consent form.

Data were collected by means of three questionnaires, in the following sequence: Morisky Green test, to assess pharmacological adherence (dependent variable); an instrument to assess the variables that interfere with patient adherence and a questionnaire to assess patient knowledge about CAD.

The four-item Morisky Green Test (Morisky Medication Adherence Scale - MMAS-4) was developed in 1986(1414 Morisky DE, Green LW, Levine DM. Concurrent and predictive validity of self-reported measure of medication adherence. Med Care. 1986;24(1):67–74. doi: 10.1097/00005650-198601000-00007
https://doi.org/10.1097/00005650-1986010...
) and is one of the most often used in Brazil(77 Birck MG, Goulart AC, Lotufo PA, Bensenor IM. Secondary prevention of coronary heart disease: a cross-sectional analysis on the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Sao Paulo Med. J. 2019;137(3):223-33. doi: https://doi.org/10.1590/1516-3180.2018.0531140319
https://doi.org/10.1590/1516-3180.2018.0...
,1515 Oscalices MIL, Okuno MFP, Lopes MCBT, Batista REA, Campanharo CRV. Health literacy and adherence to treatment of patients with heart failure. Rev Esc Enferm USP. 2019;53:e03447. doi: http://dx.doi.org/10.1590/S1980-220X2017039803447
http://dx.doi.org/10.1590/S1980-220X2017...

16 Alves KB, Guilarducci NV, Santos TR, Baldoni AO, Otoni A, Pinto SWL, et al. Existe associação entre qualidade de vida e adesão à farmacoterapia em pacientes com doença renal crônica em hemodiálise?. Einstein (São Paulo). 2018;16(1):eAO4036. https://doi.org/10.1590/S1679-45082018AO4036
https://doi.org/10.1590/S1679-45082018AO...
-1717 Albuquerque NLS, Oliveira ASS, Silva JM, Araújo TL. Association between follow-up in health services and antihypertensive medication adherence. Rev Bras Enferm. 2018;71(6):3006-12. doi: https://doi.org/10.1590/0034-7167-2018-0087
https://doi.org/10.1590/0034-7167-2018-0...
) for the indirect measurement of pharmacological adherence behavior. It consists of four questions with dichotomous answers (yes/no). The patients were considered nonadherent whenever they answered “yes” to any of the questions(1414 Morisky DE, Green LW, Levine DM. Concurrent and predictive validity of self-reported measure of medication adherence. Med Care. 1986;24(1):67–74. doi: 10.1097/00005650-198601000-00007
https://doi.org/10.1097/00005650-1986010...
). The instrument is reliable, with adequate internal consistency and stability, assessed by a Cronbach’s alpha of 0.73 (0.67-0.79) and by the test and retest (r=0.70, p=0.02), respectively(1818 Ben AJ, Neumann CR, Mengue SS. The Brief Medication Questionnaire and Morisky Green Test to evaluate medication adherence. Rev Saúde Pública. 2012;46:279-89. doi: https://doi.org/10.1590/S0034-89102012005000013
https://doi.org/10.1590/S0034-8910201200...
).

The independent variables were assessed through a questionnaire about the factors that can potentially interfere with adherence. The questionnaire was developed by the researchers based on the literature(77 Birck MG, Goulart AC, Lotufo PA, Bensenor IM. Secondary prevention of coronary heart disease: a cross-sectional analysis on the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Sao Paulo Med. J. 2019;137(3):223-33. doi: https://doi.org/10.1590/1516-3180.2018.0531140319
https://doi.org/10.1590/1516-3180.2018.0...
,1919 Galdeano LE, Rossi LA, Pelegrino FM. Content validation of the deficient knowledge nursing diagnosis. Acta Paul Enferm. 2008;21(4):549-55. doi: 10.1590/S0103-21002008000400003
https://doi.org/10.1590/S0103-2100200800...
). The factors were subdivided into five categories, according to the dimensions proposed by the WHO(66 World Health Organization (WHO). Adherence to longterm therapies: evidence for action. [Internet]. Geneva: WHO; 2003 [cited Jun 18, 2017]. Available from: https:// www.who.int/chp/knowledge/publications/adherence_report/en/
www.who.int/chp/knowledge/publications/a...
):
  1. patient-related variables: gender; age; ethnicity; marital status; education; number of children; religious beliefs; family assistance in the treatment (financial, company during consultation, change in eating habits and incentive to treatment – with the possibility of selecting more than one option); experience with the disease in the family context; patient’s perceived health and knowledge about the disease.

  2. variables related to socioeconomic level: family income; costs of the medications purchased with own money; employment situation; type of housing and transportation costs.

  3. variables related to the disease: time since diagnosis; absence of symptoms, previous hospitalization and previous invasive treatment (coronary artery bypass grafting and/or percutaneous coronary intervention).

  4. treatment-related variables: undesirable effects; complex therapeutic regimens (self-declaration by the participants of considering the treatment difficult in relation to the number and frequency of medication taking); length of treatment; use of other forms of treatment and lifestyle change.

  5. variables related to the health care system and team: access to the health care service; time spent to reach the health care service; waiting time for the next appointment versus service time and the relationship with the health care team.

Knowledge about the disease was assessed using five questions from the Questionnaire for Assessment of Knowledge in Relation to Disease, developed and submitted to content validation by Galdeano(1919 Galdeano LE, Rossi LA, Pelegrino FM. Content validation of the deficient knowledge nursing diagnosis. Acta Paul Enferm. 2008;21(4):549-55. doi: 10.1590/S0103-21002008000400003
https://doi.org/10.1590/S0103-2100200800...
). The questions assess familiarity with the name of the disease; description of risk factors; description of signs and symptoms; description of measures to minimize disease progression and description of signs and symptoms of disease complication(1919 Galdeano LE, Rossi LA, Pelegrino FM. Content validation of the deficient knowledge nursing diagnosis. Acta Paul Enferm. 2008;21(4):549-55. doi: 10.1590/S0103-21002008000400003
https://doi.org/10.1590/S0103-2100200800...
). The result was analyzed according to what was proposed by the author(1919 Galdeano LE, Rossi LA, Pelegrino FM. Content validation of the deficient knowledge nursing diagnosis. Acta Paul Enferm. 2008;21(4):549-55. doi: 10.1590/S0103-21002008000400003
https://doi.org/10.1590/S0103-2100200800...
): answering the entire question correctly: 1.0 point; answering half the question correctly: 0.5 points; answer a quarter of the question correctly: 0.25 points; answering the question incorrectly or not knowing how to answer it: 0 points. Thus, patients who scored ≤ 3 were considered to have deficient knowledge about the disease(1919 Galdeano LE, Rossi LA, Pelegrino FM. Content validation of the deficient knowledge nursing diagnosis. Acta Paul Enferm. 2008;21(4):549-55. doi: 10.1590/S0103-21002008000400003
https://doi.org/10.1590/S0103-2100200800...
).

The data were analyzed using the R 3.4.1 software and the qualitative variables were summarized by means of relative and absolute frequencies and the quantitative variables were expressed by means of measures of central tendency and dispersion [mean, standard deviation (SD), median and quartiles]. The Student’s t-test for independent samples or Mann-Whitney’s U test were used to determine the association between the quantitative variables and medication adherence, according to the distribution of the variables. Pearson’s Chi-Square test was used to determine the association of the qualitative variables with medication adherence. The Bonferroni’s correction was used to compare the alcohol intake categories two by two (never drank, stopped drinking or still drinking) and determine which comparisons were significantly different.

The Cox model with constant times and robust variance was adopted to assess the joint association between different variables and pharmacological adherence, with Prevalence Ratios (PRs) being assessed with 95% Confidence Intervals (CIs). A significance level of 5% was considered.

This study was approved by the Research Ethics Committees of the Federal University of São Paulo (Protocol No. 1.676.061) and of the Beneficência Portuguesa Hospital (Protocol No. 1.709.442). The study followed all legal prerogatives of research involving human beings.

Results

A total of 198 patients were considered eligible. All agreed to participate in the study and there were no exclusions. Most were male (64.6%), married (70.2%), Catholic (62.6%), Caucasian (74.2%) and with a family history of CAD (70.7%). The mean age was 65.75 (SD=11.41 years old); the mean number of years studied was 7.27 (SD=5.41) and the mean number of children was 2.89 (SD=1.80) (Table 1).

Table 1
Association between pharmacological adherence and the factors related to the patient (n=198). São Paulo, SP, Brazil, 2017-2018

With regard to socioeconomic support, most patients were retired/inactive, had a family income of 1 to 3 minimum wages, had their own homes and needed family financial supplementation for the purchase of medications (Table 2).

Table 2
Association between pharmacological adherence and the factors related to the patient's socioeconomic support (n=198). São Paulo, SP, Brazil, 2017-2018

The mean time since the diagnosis was 85.1 months, ranging from 6 to 480 months. The mean duration of treatment was 82.4 months (6 - 480 months). One hundred and seventy-five patients (88.4%) had satisfactory knowledge about the disease and the mean knowledge score about the disease was 4.45 points (SD=0.83).

Most patients were non-compliant (n=113; 57.1%). Among the reasons for non-adherence, 99 (87.6%) reported forgetting to take the medication on time, 60 (53%) did not remember to take it, 26 (23%) interrupted it when they felt well and five (4.4%) reported neglecting the time to take their medications.

In the univariate analysis of the factors related to the patient and the socioeconomic situation, no significant association was found (Tables 1 and 2).

Table 3 shows that 164 patients (82.8%) had symptoms. Fatigue and palpitation were significantly associated with pharmacological adherence. With regard to invasive treatment, 158 (79.8%) underwent some type of intervention, among which 77 (48.7%) only underwent coronary artery bypass grafting, 47 (29.7%) only underwent percutaneous coronary intervention and 34 (21.5%) underwent both treatments. There was no significant association between this variable and adherence to the pharmacological treatment.

Table 3
Association between pharmacological adherence and the factors related to the patient's disease (n=198). São Paulo, SP, Brazil, 2017-2018

Table 4 shows that never having consumed alcohol and being served by health insurance was significantly associated with pharmacological adherence. The factors associated with lack of pharmacological adherence were the following: considering the treatment complex; having stopped drinking alcohol or still drinking alcohol and being served in the public health care service.

Table 4
Association between pharmacological adherence and the factors related to patient treatment (n=198), the health care service and the relationship with the health care team. São Paulo, SP, Brazil, 2017-2018

In the multiple analysis, it was found that patients with fatigue and palpitation had a three-fold increase in the prevalence of medication adherence. In contrast, alcohol consumption was associated with decreased adherence, so that patients who drank had a 2.88 times greater chance of non-adherence than those who did not drink (Table 5).

Table 5
Multiple analysis of the factors associated with patient pharmacological adherence (n=198). São Paulo, SP, Brazil, 2017-2018

Discussion

This study found that most patients with CAD did not adhere to drug treatment. In addition, the majority believed that they used the prescribed medications correctly. This result can be related to the fact that the patients did not consider it lack of adherence when they forget to take their medications at the prescribed times. Other studies have also shown that a large number of patients reported neglecting the medication schedule(88 Santos VB, Silva LL, Guizilini S, Valente IB, Barbosa CB, Carneiro TAB, et al. Adherence to antiplatelet and statin therapy by patients with Acute Coronary Syndrome following discharge. Enferm Clin. 2020;pii:S1130-8621(20)30237-0. doi: 10.1016/j.enfcli.2020.02.020
https://doi.org/10.1016/j.enfcli.2020.02...
,1010 Wu Q, Zhang D, Zhao Q, Liu L, He Z, Chen Y, et al. Effects of transitional health management on adherence and prognosis in elderly patients with acute myocardial infarction in percutaneous coronary intervention: a cluster randomized controlled trial. PLoS One. 2019;14(5):e0217535. doi:10.1371/journal.pone.0217535
https://doi.org/10.1371/journal.pone.021...
,2020 Krack G, Holle R, Kirchberger I, Kuch B, Amann U, Seidl H. Determinants of adherence and effects on health-related quality of life after myocardial infarction: a prospective cohort study. BMC Geriatr. 2018;18(1):136. doi: 10.1186/ s12877-018-0827-y
https://doi.org/10.1186/s12877-018-0827-...
).

Regarding the pharmacological treatment, the mean duration of this treatment was less than the time since the diagnosis. This can occur because, at some point, many patients interrupt treatment due to lack of financial resources(88 Santos VB, Silva LL, Guizilini S, Valente IB, Barbosa CB, Carneiro TAB, et al. Adherence to antiplatelet and statin therapy by patients with Acute Coronary Syndrome following discharge. Enferm Clin. 2020;pii:S1130-8621(20)30237-0. doi: 10.1016/j.enfcli.2020.02.020
https://doi.org/10.1016/j.enfcli.2020.02...
), the belief that treatment would be unnecessary while they are asymptomatic or to the complex therapeutic scheme, with associated side effects(2121 Burkauskas J, Bunevičius A, Brožaitienė J, Neverauskas J, Fineberg FA, Wellsted D, et al. Exploring Cognitive Concomitants of Mental Fatigue in Patients with Coronary Artery Disease. Neuropsychobiology. 2017;76(3):151-60. doi: 10.1159/000489713
https://doi.org/10.1159/000489713...
).

The proportion of patients who adhered to pharmacological treatment in this study (43%) was lower than that found in another Brazilian state, in which 56.5% of the patients with CAD were adherent to treatment(77 Birck MG, Goulart AC, Lotufo PA, Bensenor IM. Secondary prevention of coronary heart disease: a cross-sectional analysis on the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Sao Paulo Med. J. 2019;137(3):223-33. doi: https://doi.org/10.1590/1516-3180.2018.0531140319
https://doi.org/10.1590/1516-3180.2018.0...
). However, patient adherence in our study was greater than that of another Brazilian study on adherence to treatment by patients with CAD (26%)(99 Sobral PD, Gomes ED, Carvalho PO, Godoi ET, Oliveira DC. Prevalência de adesão medicamentosa em pacientes com doença arterial coronariana crônica. Enferm Brasil 2020;19(2):98-104. doi: https://doi.org/10.33233/eb.v19i2.2137
https://doi.org/10.33233/eb.v19i2.2137...
) or other chronic diseases (30.8%)(1818 Ben AJ, Neumann CR, Mengue SS. The Brief Medication Questionnaire and Morisky Green Test to evaluate medication adherence. Rev Saúde Pública. 2012;46:279-89. doi: https://doi.org/10.1590/S0034-89102012005000013
https://doi.org/10.1590/S0034-8910201200...
). These discrepancies reinforce the importance of further studies on the factors that can interfere with adherence to treatment by patients with CAD in Brazil, whose results may contribute to explain the differential prevalence.

Among the variables related to the disease, fatigue and palpitation were significantly associated with adherence in the univariate analysis and remained associated in the multiple analysis. Fatigue is a prevalent, disabling and persistent symptom in patients with CAD(2121 Burkauskas J, Bunevičius A, Brožaitienė J, Neverauskas J, Fineberg FA, Wellsted D, et al. Exploring Cognitive Concomitants of Mental Fatigue in Patients with Coronary Artery Disease. Neuropsychobiology. 2017;76(3):151-60. doi: 10.1159/000489713
https://doi.org/10.1159/000489713...
). In a study conducted with patients undergoing percutaneous coronary intervention, this symptom was associated with the side effects of the medications(2222 Pettersen TR, Fridlund B, Bendz B, Nordrehaug JE, Rotevatn S, Schjøtt J, et al. Challenges adhering to a medication regimen following first-time percutaneous coronary intervention: A patient perspective. Int J Nurs Stud. 2018;88:16-24. doi: 10.1016/j. ijnurstu.2018.07.013
https://doi.org/10.1016/j.ijnurstu.2018....
). Fatigue has also been identified as a predictor of worsening quality of life in patients newly diagnosed with CAD and in patients with chronic CAD(44 Thygesen K, Alpert JS, Jaffe AS, Chaitman BR, Bax JJ, Morrow DA, et al. Fourth Universal Definition of Myocardial Infarction. J Am Coll Cardiol. 2018;72(18):2231-64. doi: 10.1016/j.jacc.2018.08.1038
https://doi.org/10.1016/j.jacc.2018.08.1...
). This symptom also impairs psychosocial and physiological functionality(2323 Johnston S, Eckhardt AL. Fatigue and acute coronary syndrome: a systematic review of contributing factors. Heart Lung. 2018;47(3):192-204. doi: 10.1016/j. hrtlng.2018.03.005
https://doi.org/10.1016/j.hrtlng.2018.03...
-2424 Blakeman JR, Stapleton SJ. An integrative review of fatigue experienced by women before and during myocardial infarction. J Clin Nurs. 2018;27(5-6):906-16. doi: 10.1111/ jocn.14122
https://doi.org/10.1111/jocn.14122...
). Other symptoms, such as palpitation, can occur both in the initial stage of the disease, due to arrhythmias related to a recent AMI and in advanced stages of chronic CAD, due to increased areas of ischemia and consequent fibrosis(33 Knuuti J, Wijns W, Saraste A, Capodanno D, Barbato E, Funck-Brentano C, et al. 2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes. Eur Heart J. 2020;41(3):407-77. doi: 10.1093/eurheartj/ ehz425
https://doi.org/10.1093/eurheartj/ehz425...
). Both symptoms generate physical discomfort, which imposes restrictions on routine habits. Thus, the individuals tend to adhere more to the treatment in order to avoid these discomforts(2525 Ammouri AA, Al-Daakak ZM, Isac C, Gharaibeh H, Al-Zaru I. Symptoms experienced by Jordanian men and women after coronary artery bypass graft surgery. Dimens Crit Care Nurs. 2016;35(3):125-32. doi: 10.1097/DCC.0000000000000175
https://doi.org/10.1097/DCC.000000000000...
). On the other hand, asymptomatic patients who do not adhere to treatment report that, due to the absence of symptoms, they interrupt the medications without consulting a professional, as they feel healthy(1111 Du L, Cheng Z, Zhang Y, Li Y, Mei D. The impact of medication adherence on clinical outcomes of coronary artery disease: A meta-analysis. Eur J Prev Cardiol. 2017;24(9):962-70. doi: 10.1177/2047487317695628
https://doi.org/10.1177/2047487317695628...
).

Patients who had never ingested it were almost three times more likely to have drug adherence than those who had ingested it, a finding also identified previously(88 Santos VB, Silva LL, Guizilini S, Valente IB, Barbosa CB, Carneiro TAB, et al. Adherence to antiplatelet and statin therapy by patients with Acute Coronary Syndrome following discharge. Enferm Clin. 2020;pii:S1130-8621(20)30237-0. doi: 10.1016/j.enfcli.2020.02.020
https://doi.org/10.1016/j.enfcli.2020.02...
,2626 Chung PW, Yoon BW, Lee YB, Shin BS, Kim HY, Park JH, et al. Medication Adherence of Statin Users after Acute Ischemic Stroke. Eur Neurol. 2018;80(1-2):106-14. doi: 10.1159/000493530
https://doi.org/10.1159/000493530...
). A study(2626 Chung PW, Yoon BW, Lee YB, Shin BS, Kim HY, Park JH, et al. Medication Adherence of Statin Users after Acute Ischemic Stroke. Eur Neurol. 2018;80(1-2):106-14. doi: 10.1159/000493530
https://doi.org/10.1159/000493530...
) showed that alcoholism is associated with lack of adherence to the pharmacological treatment of arterial hypertension and that patients who consume alcohol had a risk of non-adherence almost six times greater than those who do not drink. The reason would be the fear of the possible undesirable effects of the association of antihypertensive medications with alcoholic beverages.

Other variables related to adherence to treatment in the univariate analysis were the following: considering the treatment complex; assistance in the public health care system and in health care insurance. The patients who considered the treatment complex were less compliant and reported forgetting or neglecting taking medication, shortages and difficulty in their routine. The complex dosing schedule with a larger number of medications used tends to reduce adherence(2626 Chung PW, Yoon BW, Lee YB, Shin BS, Kim HY, Park JH, et al. Medication Adherence of Statin Users after Acute Ischemic Stroke. Eur Neurol. 2018;80(1-2):106-14. doi: 10.1159/000493530
https://doi.org/10.1159/000493530...
-2727 Cordero A, Padial LR, Batalla A, Barreiro LL, Calvo FT, Castellano JM, et al. Optimal pharmacological treatment and adherence to medication in secondary prevention of cardiovascular events in Spain: Results from the CAPS study. Cardiovasc Ther. 2017;35(2):1-7. doi: 10.1111/1755-5922.12240
https://doi.org/10.1111/1755-5922.12240...
). An important aspect of the treatment that facilitates adherence, especially in the geriatric population, is the simplification of the therapeutic regimen, with the use of drugs in fixed dose combinations in a single presentation and with a lower number of daily doses, preferably in a single dose(2828 Cimmaruta D, Lombardi N, Borghi C, Rosano G, Rossi F, Mugelli A. Polypill, hypertension and medication adherence: The solution strategy? Int J Cardiol. 2018;252:181-6. doi: 10.1016/j.ijcard.2017.11.075
https://doi.org/10.1016/j.ijcard.2017.11...
-2929 Mzoughi K, Zairi I, Jemai A, Ben Kilani M, Ben Daamar H, Ben Gaied Hassine E, et al. Factors associated with poor medication compliance in hypertensive patients. Tunis Med. 2018;96(6):385-90. Available from: https://www.latunisiemedicale.com/article-medicale-tunisie_3406_fr
https://www.latunisiemedicale.com/articl...
).

Regarding the access to the health care services, it was found that the patients treated by the public health care system were less compliant than those treated by health insurance companies. A study carried out with outpatients showed that those who did not have a health care plan had a 30% greater chance of not adhering to the treatment (p=0.03)(1616 Alves KB, Guilarducci NV, Santos TR, Baldoni AO, Otoni A, Pinto SWL, et al. Existe associação entre qualidade de vida e adesão à farmacoterapia em pacientes com doença renal crônica em hemodiálise?. Einstein (São Paulo). 2018;16(1):eAO4036. https://doi.org/10.1590/S1679-45082018AO4036
https://doi.org/10.1590/S1679-45082018AO...
). Another study found a relationship between low adherence to treatment and assistance by the public health service (p=0.027)(1717 Albuquerque NLS, Oliveira ASS, Silva JM, Araújo TL. Association between follow-up in health services and antihypertensive medication adherence. Rev Bras Enferm. 2018;71(6):3006-12. doi: https://doi.org/10.1590/0034-7167-2018-0087
https://doi.org/10.1590/0034-7167-2018-0...
).

This result can be explained by the fact that the intervals between medical appointments of public health care services are often over six months, in addition to the low professional bond caused by the turnover of professionals. A study conducted with patients with hypertension showed that the chance of low pharmacological adherence follow-up with more than one physician increased by three times(3030 Ambrosetti M, Abreu A, Corrà U, Davos CH, Hansen D, Frederix I, et al. Secondary prevention through comprehensive cardiovascular rehabilitation: From knowledge to implementation. 2020 update. A position paper from the Secondary Prevention and Rehabilitation Section of the European Association of Preventive Cardiology. Eur J Prev Cardiol. 2020;204748732091337. doi: 10.1177/2047487320913379
https://doi.org/10.1177/2047487320913379...
). Other studies also emphasize that the difficulty of physical access (due to distance or limited means of transportation) and the difficulties in accessing the medications also contribute to lack of adherence(88 Santos VB, Silva LL, Guizilini S, Valente IB, Barbosa CB, Carneiro TAB, et al. Adherence to antiplatelet and statin therapy by patients with Acute Coronary Syndrome following discharge. Enferm Clin. 2020;pii:S1130-8621(20)30237-0. doi: 10.1016/j.enfcli.2020.02.020
https://doi.org/10.1016/j.enfcli.2020.02...
,1717 Albuquerque NLS, Oliveira ASS, Silva JM, Araújo TL. Association between follow-up in health services and antihypertensive medication adherence. Rev Bras Enferm. 2018;71(6):3006-12. doi: https://doi.org/10.1590/0034-7167-2018-0087
https://doi.org/10.1590/0034-7167-2018-0...
). The individuals who have a health insurance tend to use the services more and, in turn, attend to medical appointments more often, thereby increasing the opportunity to access information that can support adherence(1010 Wu Q, Zhang D, Zhao Q, Liu L, He Z, Chen Y, et al. Effects of transitional health management on adherence and prognosis in elderly patients with acute myocardial infarction in percutaneous coronary intervention: a cluster randomized controlled trial. PLoS One. 2019;14(5):e0217535. doi:10.1371/journal.pone.0217535
https://doi.org/10.1371/journal.pone.021...
). One of the main benefits of easy access to the health care services is the possibility of therapeutic adjustments and monitoring(1717 Albuquerque NLS, Oliveira ASS, Silva JM, Araújo TL. Association between follow-up in health services and antihypertensive medication adherence. Rev Bras Enferm. 2018;71(6):3006-12. doi: https://doi.org/10.1590/0034-7167-2018-0087
https://doi.org/10.1590/0034-7167-2018-0...
).

Multi-professional interventions and a more constant follow-up of these patients in secondary prevention programs can contribute to minimize modifiable risk factors. These factors include the use of alcohol, management of treatment complexity and inadequate understanding that the treatment is not necessary during the absence of symptoms.

Multi-professional programs have shown satisfactory results when incorporating face-to-face and telephone consultations, in addition to implementing technologies, such as sending messages to reinforce the importance of medication and/or implementing software programs with alarm sensors for medication schedules(3030 Ambrosetti M, Abreu A, Corrà U, Davos CH, Hansen D, Frederix I, et al. Secondary prevention through comprehensive cardiovascular rehabilitation: From knowledge to implementation. 2020 update. A position paper from the Secondary Prevention and Rehabilitation Section of the European Association of Preventive Cardiology. Eur J Prev Cardiol. 2020;204748732091337. doi: 10.1177/2047487320913379
https://doi.org/10.1177/2047487320913379...

31 Santo K, Chow CK, Thiagalingam A, Rogers K, Chalmers J, Redfern J. MEDication reminder APPs to improve medication adherence in Coronary Heart Disease (MedApp-CHD) Study: a randomised controlled trial protocol. BMJ Open. 2017;7(10):e017540. doi: 10.1136/ bmjopen-2017-017540
https://doi.org/10.1136/bmjopen-2017-017...
-3232 Santo K, Singleton A, Rogers K, Thiagalingam A, Chalmers J, Chow CK, et al. Medication reminder applications to improve adherence in coronary heart disease: a randomised clinical trial. Heart. 2019;105(4):323-9. doi: 10.1136/heartjnl-2018-313479
https://doi.org/10.1136/heartjnl-2018-31...
). A randomized clinical trial evaluated adherence to drug treatment in three different groups (Group 1: patients in usual care; Group 2: patients who used an application software without interacting with health care professionals; Group 3: patients who used an application software and interacted with the professionals). The results showed that the patients in the groups that used the application had increased medication adherence after three months of intervention, demonstrating that technology helps the patient remember the use of the medications and is effective in increasing medication adherence(3131 Santo K, Chow CK, Thiagalingam A, Rogers K, Chalmers J, Redfern J. MEDication reminder APPs to improve medication adherence in Coronary Heart Disease (MedApp-CHD) Study: a randomised controlled trial protocol. BMJ Open. 2017;7(10):e017540. doi: 10.1136/ bmjopen-2017-017540
https://doi.org/10.1136/bmjopen-2017-017...
).

In the context of multi-professional programs, knowing the factors associated with lack of medication adherence helps direct educational interventions by hospital and outpatient health care professionals, with a view to adapting adherence to the pharmacological treatment of CAD and, consequently, delaying the progression of the disease, reducing new cardiovascular events and improving the patient’s quality of life.

The data in this study must be considered in the light of some limitations. First, it was carried out in a single center, which hinders the generalization of the results. In addition, the prevalence of adherence can be overestimated, since social desirability may have influenced the patients’ self-report in the Morisky Green Test. Multicenter studies in the country must be performed using objective measures of medication adherence, such as serum dosage or vials with electronic dose monitoring.

Despite its limitations, this study evaluated several variables related to adherence, as recommended by the WHO, unlike other, which assessed only a few factors that interfere with adherence. From the data identified, the need is reasserted for nurses to assess the patient globally, in the multidisciplinary context, so that they may be aware of detailed aspects related to medication adherence and establish interventions to address such factors.

Conclusion

More than half of the hospitalized patients with CAD did not adhere to the pharmacological treatment. The factors associated with adequate pharmacological adherence were the following: fatigue and palpitation, never having consumed alcohol and being served by health care insurance. The factors associated with lack of pharmacological adherence were the following: considering the treatment complex, using or having used alcoholic beverages and being served in the public health care service. The presence of fatigue and palpitation remained as factors associated with pharmacological adherence in the multiple analysis and alcohol consumption remained as a factor associated with lack of pharmacological adherence.

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    Santo K, Singleton A, Rogers K, Thiagalingam A, Chalmers J, Chow CK, et al. Medication reminder applications to improve adherence in coronary heart disease: a randomised clinical trial. Heart. 2019;105(4):323-9. doi: 10.1136/heartjnl-2018-313479
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Edited by

Associate Editor: Maria Lúcia do Carmo Cruz Robazzi

Publication Dates

  • Publication in this collection
    03 Sept 2021
  • Date of issue
    2021

History

  • Received
    13 July 2020
  • Accepted
    26 Dec 2020
Escola de Enfermagem de Ribeirão Preto / Universidade de São Paulo Av. Bandeirantes, 3900, 14040-902 Ribeirão Preto SP Brazil, Tel.: +55 (16) 3315-3451 / 3315-4407 - Ribeirão Preto - SP - Brazil
E-mail: rlae@eerp.usp.br