Pharmacist intervention to improve adherence to medication among heart failure patients at North East Ethiopia hospital

Heart failure (HF) is a major and growing medical problem and its management is still challenging due to the coexistence of complications, co‐morbidity, and medication non‐adherence. HF patients who are adherent to their medication have fewer HF exacerbations, improved survival, and lower healthcare expenditure. Adherence to HF medication plays a pivotal role in attaining maximal therapeutic outcomes. The aim was to assess the medication adherence of heart failure patients at Debre Berhan Comprehensive Specialized Hospital (DBCSH). A pre‐post interventional study was undertaken from July 1, 2022, to December 31, 2022, at the medical referral clinic of DBCSH. The educational interventions were provided for 6 months. Medication adherence was determined using the Morisky Green Levin Medication Adherence Scale (MGLS). The data was entered into Epidata version 4.2.0 and analyzed using SPSS version 25.0 statistical software. Descriptive statistics and binary logistic regression analysis were performed. The strength of the association between predictor variables and outcome variables was determined using a 95% confidence interval and adjusted odd ratio. In the pre‐intervention phase, 54.6% of patients had medium medication adherence, while in the post‐intervention phase, 36.4% of patients had high medication adherence and 61.9% of patients had medium medication adherence. Following the intervention, medication cost (120, 50%), inadequate availability of drugs (75, 31%), and forgetfulness (30, 13%) were the main reasons for medication non‐adherence. The presence of co‐morbidity and the number of co‐morbidity (p < .05) were significantly associated with the occurrence of decreased medication adherence in the pre‐intervention phase. Interventions by pharmacists to educate HF patients about the nature of their disease and providing brochures to increase awareness of their medications have been shown to improve medication adherence.


| INTRODUC TI ON
Globally, cardiovascular diseases (CVDs) are the leading cause of death and an estimated 17.9 million people died from CVDs in 2019, over three-quarters of which took place in low-and middle-income countries.In 2019, out of the 17 million premature deaths (under the age of 70) due to non-communicable diseases, 38% were caused by CVDs. 1 In Ethiopia, there is little evidence about the burden of CVD.A study conducted using the 2017 global burden of disease, injuries, and risk factors (GDB) reported that CVD prevalence was 5534 per 100 000 population. 2 Heart failure (HF) is one of the most prevalent types of CVD, resulting in a major medical and economic problem. 3It is a progressive clinical syndrome that can result from any changes in cardiac structure or function that impair the ability of the ventricle to fill with or eject blood. 4The incidence and prevalence of HF are increasing, approximately 6.5 million Americans have HF with 1 000 000 new cases diagnosed each year, with over 30 billion US dollars in annual expenditures. 5Based on the phenotypes of the disease, HF can be classified as HF with a preserved ejection fraction (EF) (HFpEF), HF with a reduced EF (HFrEF), acute decompensated HF (ADHF), and advanced HF. 6 Many patient factors should be considered when selecting HF medications.These factors include compelling indications, comorbid disease states, concomitant medications use, cost of medication, and medication adherence. 7art failure management is still challenging due to the coexistence of complications and co-morbidity. 8In addition, prescribing a higher number of medications for HF patients has also been associated with negative health outcomes, frequent hospitalization, waste of resources, and patient non-adherence to their drug regimens. 9So, HF guidelines recommend adherence to prescribed medications and optimized self-care measures are useful for HF patient prognosis. 10,11herence is defined by the World Health Organization (WHO) as "the extent to which a person's behavior taking medication, following a diet, and/or executing lifestyle changes, corresponds with agreed recommendations from a health care provider". 12,13Heart failure patients who were adherent to their medications improved patient clinical outcomes. 146][17] Non-adherence to HF medication is associated with increased hospitalization, 18,19 worsening symptoms, increased disease progression, and an overall increase in healthcare costs 18 and emergency visits. 20[23][24][25][26] To reach targeted therapeutic outcomes and reduce medication non-adherence issues of HF patients, pharmacist-led implementation of medication therapy management (MTM) service has paramount importance.
[29] A prospective interventional randomized control trial conducted in the USA showed, 67.9% (n = 122) and 78.8% (n = 192) of medication adherence in the usual care and the intervention groups, respectively. 30In addition, another prospective interventional study reported, 58.5% (n = 139) and 75.7% (n = 140) of medication adherence in the control and the intervention group, respectively. 31udies are available on the implementation of pharmacist intervention in different developed countries.However, there are no studies conducted in resource-constrained countries such as Ethiopia.This study aimed to assess pharmacist interventions to improve medication adherence of HF patients at the medical referral clinic of DBCSH, Ethiopia.

| Study setting, design, and population
A pre-post interventional study was undertaken from July 1, 2022, to December 30, 2022, at DBCSH.The medical referral clinic is one of the specialty clinics in DBCSH providing cardiac care.All ambulatory HF patients who attended the medical referral clinic of DBCSH ≥18 years old and HF patients who had complete medical records were included in the study.Patients who could not stand the interview and patients who changed follow-up sites were excluded from the study.

| Sample size determination and sampling technique
The sample size was estimated using a single population proportion formula. 32Using a 50% prevalence of medication adherence, and adding 10% of the contingency, the calculated final sample size was 423.
Study participants were selected using a systematic random sampling technique using the Health Management Information Systems (HMIS) list of HF patients at a medical referral clinic of DBCSH on each day of the data collection period.

| Data collection procedures and tools
Study participant's demographic and clinical data were collected using a pre-tested structured questionnaire and data abstraction tools, respectively.Trained two clinical pharmacists and three nurses carried out the data collection.The clinical pharmacists were involved in clinical data review and patient education, and the nurses were involved in patient interviews.

Medication adherence was determined using the Morisky Green Levin Medication Adherence Scale (MGL). It has four items
focusing on past medication use patterns with closed dichotomies (yes/no).Each "no" response was rated as 1 and each "yes" response was rated as 0. The total summed score ranges from 0 to 4 and was grouped into high adherence (0 points scored), medium adherence (1-2 points scored), and poor adherence (≥3 points scored). 33

| Interventions
On the day of the patient appointment, patient demographic data and pre-intervention medication adherence data were collected.
We provided education services about over-the-counter (OTC) drug use, diet modifications (including salt restriction), physical activity, and self-monitoring of weight.In addition, based on the standard HF treatment guidelines 10,34,35 trained data collectors provide verbal education about the importance of medication adherence.
Study participants received brochures that contained specific information about HF and HF medications as an intervention package to improve medication adherence and lifestyle modifications.
Time spent with each participant was 16-21 min for a medication review and interview, and 14-21 min for intervention and documentation both in pre-and post-intervention phases.

| Outcome measures
The change in medication adherence rate was the main outcome measured from pre-intervention (baseline) to post-intervention.The change in medication adherence rate was determined by MGLS. 33

| Data analysis and interpretations
The collected data were sorted, cleaned, coded, and entered into Epidata version 4. Binary logistic regression analysis was performed to show the association between predictors' variables with medication adherence.
All variables with p < .25 in the univariable binary logistic regression analysis were included in the multivariable binary logistic regression analysis, which was performed to determine the potential predictors of medication adherence.A p-value of <.05 was considered statistically significant.

| Socio-demographic characteristics of study participants
As per the eligibility criteria, 11 study participants were excluded out of 423 recruited patients.The mean age of study participants was 44.57(SD, 17.4) years and most of them were in the age range of 18-93 years.The majority of the study participants were paid out of pocket for their medication (54.6%).About 60.4% of participants resided in urban areas (Table 1).

| Clinical characteristics
The greater proportion of patients (33.5%, 138) had 5-10 years of HF duration.The mean duration of HF treatment was 9.45 years (SD, 6.47) with a range of 1-35 years.More than one third of patients (30.6%, 126) did not have co-existing co-morbidities and nearly one fourth of patients (23.5%, 97) had three co-morbidities.More than half of the patients (56.8%, 234) had taken 2-4 drugs (Table 2).
Nearly two thirds, (63.6%, 262) of the study participants had no agreed exercise plan with physicians.The majority of patients (73.1%, 301) had agreed on dietary plans with physicians.
Study participants had received an average of four drugs.

| Medication adherence
In the pre-intervention, 54.6% of study participants had medium medication adherence and 39.1% had low medication adherence.

| Reasons for medication non-adherence
Forgetfulness (40%) was the main reason, followed by inadequate availability of medications (29%), and the cost of medication too expensive (22%) in the pre-intervention.Following the intervention, forgetfulness came down to 13%, although medication cost (50%, 120) went up and inadequate availability (31%, 75) remained almost similar (Table 4).

| Predictors of medication adherence
From clinical and socio-demographic characteristics incorporated in the logistic regression analysis, the number of co-morbidities, number of drugs prescribed, and the presence of drug-drug interaction(DDI) were significantly associated with medication adherence (p < .05) in the post-intervention, whereas, the presence of co-morbidity and number of co-morbidity were significantly associated with medication adherence in the pre-intervention (Table 5).
During pre-intervention, patients who had co-morbidity were 0.69 times less likely to be adherent to medication compared with patients who had no co-morbidity (AOR = 0.68, 95% CI: 0.44-0.90).
In addition, the number of co-morbidity increased by one unit the patient medication adherence decreased by 0.88 times.
Following intervention patients who had DDI were 0.62 times less likely to be adherent than patients who had no drug-drug interaction (AOR = 0.62, 95% CI: 1.02-3.13).Patients who took ≥5 drugs were 0.32 times less likely to be adherent compared with patients who had taken one drug (AOR = 0.32, 95% CI: 1.59-5.22)(Table 5).

| DISCUSS ION
Adherence to HF medications remains the cornerstone of preventing avoidable readmissions, premature deaths, and unnecessary healthcare expenses.In the current study, a large number of HF patients adherent at the post-intervention reflected in MGLS.Medication adherence of study participants was increased following the pharmacist's provision of intervention.7][38][39] In addition, this finding was supported by a systematic review and meta-analysis done by Ruppar et al indicated pharmacist intervention had significant effects on improving HF patients' medication adherence. 40However, it was in contrast with a study conducted in Australia indicating pharmacists discussing with patients about their medicines did not improve medication adherence.This difference may be differences in setting, participant's clinical characteristics, methods used to measure medication adherence, study design, culture of pharmacists' approach to patients, religious, and educational background of participants.In The patient prefers not to take 1 (0.1) 0 Patients felt worse when taking a drug 4 (1) 1 (0.5) addition, differences in socioeconomic status of study participants also may be contributing to medication non-adherence.
In this study, we introduced a pharmacist-led intervention to improve medication adherence.The main focus of the intervention was to resolve the problems identified in the pre-intervention phase.The Forgetfulness was the main reason that contributed to poor medication adherence in the pre-intervention.This finding was consistent with studies done in the USA. 18,26If HF patients forget to take their medications, they try to intentionally miss their medication or change the instructions provided by pharmacists.
In the post-intervention phase, the cost of medication too expensive was the main reason that contributed to poor adherence.
This finding was in line with a study conducted in Tanzania. 14ditionally, a study done in the USA 41 2.0 and then exported to Statistical Package for Social Sciences (SPSS) version 25 software.Descriptive statistics were used to summarize frequencies, means, and percentages.
patients were educated to improve awareness of their treatment, the importance of medication adherence, and self-management of their disease condition.The interventions also provided educational material to the study participants that was used to help the patients get additional information related to their treatment and disease condition.Individual patients had an opportunity to discuss with their pharmacist at three time points in the 6-month study period.Based on our findings, more contacts of patients with pharmacists have more effect on patients' awareness' of medication adherence.This finding was concordant with previous studies with interventions delivered on daily pharmacist contact, monthly pharmacist contact or telephone follow-up have improved adherence to medication with different adherence rates (46-50). 14 Socio-demographic characteristics of heart failure patients from July to December 2022.
TA B L E 1a Retired.

Reason for medication non-adherence Participants Pre-test (N %) Post-test (N %)
Clinical characteristics of heart failure patients from July to December 2022.
TA B L E 2⁎ Paired samples t-test.

32 (1.59-5.11)
Univariable and multivariable analysis of factors associated with medication adherence of heart failure patients from July to December 2022.
istics of medication (difficult schedule, frequent dosing, side effects, and difficulty swallowing), and cost of medication.Patients who had co-morbidity were 0.69 times less likely to be adherent to medications compared to patients who did not have co-morbid disease during the pre-intervention.This finding was comparable with studies done in Iran and the USA showing TA B L E 5