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Interventions for increasing medication adherence in heart failure patients: A narrative review

Libor Jelinek1, Jan Vaclavik2, Marie Lazarova2

Heart failure is one of the critical and most costly medical challenges of the 21st century. It is a chronic debilitating condition and adherence to medication, a precondition for successful treatment is often poor. There are various inter- ventions for improving the adherence. Depending on the goal of the intervention, these are roughly patient centric, healthcare provider centric and system centric. We provide an overview of these interventions with a focus on ef- fectiveness and appropriateness in different clinical situations. Their use can lead to improved patient outcomes and reduced economic burden of the disease.

Key words: pharmacotherapy, heart failure, barriers to adherence, interventions to improve adherence

Received: April 28, 2024; Revised: June 7, 2024; Accepted: June 17, 2024; Available online: July 16, 2024 https://doi.org/10.5507/bp.2024.022 © 2024 The Authors; https://creativecommons.org/licenses/by/4.0/

1Department of Exercise Medicine and Cardiovascular Rehabilitation, University Hospital Olomouc and Faculty of Medicine, Palacky University Olomouc, Olomouc, Czech Republic 2Department of Internal Medicine and Cardiology, University Hospital Ostrava and Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic Corresponding author: Libor Jelinek, e-mail: [email protected]

INTRODUCTION

Purpose and need of this paper Our aim was to provide a narrative overview of prac-

tices and interventions that have been generally shown to improve medication adherence in patients with chronic heart failure. We focused on methods that have been stud- ied for their impact on patient outcomes based on clinical trials.

Background Heart failure is one of the most prevalent chronic dis-

eases worldwide1. Although the incidence has been de- clining in recent years due to advances in the treatment of acute cardiovascular disease, the overall prevalence is increasing with an ageing population and an increased prevalence of risk factors of heart failure2,3. Khera et al. describe a reduction in the incidence of heart failure in the population of Medicare beneficiaries in the US from 35.7 cases per 1000 population to 26.5 in 2016, independ- ent of race and gender4.

Epidemiology and impact of non-adherence in heart failure

The chronic nature of heart disease implies the long- term use of medications. Despite the efficacy of these drugs, the patient does not always adhere to the treat- ment regimen. Another factor is adherence to lifestyle measures, especially salt and fluid restriction5. Medication adherence rates in patients with heart failure are highly variable depending on the population and methods used to assess them. The reported variance can be as high as

10–98% (ref.6). Low adherence increases the risk of hos- pitalisation and death7. In addition to the negative effect on patients, non-adherence also has a negative effect on healthcare systems. In sa study of Medicare beneficiaries in 4 US states, Esposito et al. found that adherent patients cost the health system 23% less (by $5,910) (ref.8).

Interventions to improve medication adherence in heart failure patients reduce very costly hospital admis- sions and mortality9.

Barriers to medication adherence Improving adherence to medication is a complex,

multi-step process. The adherence level for a particular patient can be thought of as the sum of the individual bar- riers to adherence and interventions can be interpreted as addressing these individually. The WHO divides them into five groups as socioeconomic, system-related, condition- related, therapy-related and patient-related factors10.

Different barriers can be addressed in various ways. For example, if the main reason for non-adherence is the financial cost of the treatment, then one can try to re- place the medication with cheaper options, or educate the patient about the importance of the treatment and its effect on their health, thereby increasing their willingness to pay for the drugs.

Just as one barrier can be overcome using different methods, one intervention can address multiple barriers. For example, simplifying the medication regimen can re- duce the cost, make it easier for the patient to take the therapy, and also minimize the risk of mistaking or omit- ting prescribed drugs.

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INTERVENTIONS TO IMPROVE MEDICATION ADHERENCE

There is an ongoing debate regarding the exact place of interventions to improve medication adherence in the care of patients with heart failure. There is a range of evi- dence regarding the effectiveness of such methods. These mostly involve working on the soft-skills (like commu- nication counselling) of healthcare providers, or patient education. Both are extensive topics that are difficult to implement outside of clinical trials, heart failure care cen- tres, and above all, are highly dependent on the national system of care (and the system of payment for care).

For the orientation and purposes of this paper, we have simplified a list of WHO defined barriers, and divid- ed the interventions broadly into patient-oriented, health care provider-oriented and health system-oriented, see Table 1. These are interlinked. Interventions targeting the system and healthcare providers lead to increased patient adherence to medication indirectly, see Fig. 1.

Patient-centric interventions Education

Much of the management of heart failure can and is carried out by patients themselves5. Understanding the treatment is a prerequisite for success and this can be achieved through good patient education empowering informed decisions to be made about their own health. This also leads to greater equity and improved clinical outcomes11.

In general, the more time spent with the patient and ideally the involvement of a multidisciplinary team (doctor, nurse, pharmacist), the better the outcome. A meta-analysis by Jonkman et al. involving studies of self-management interventions and education on 5624 heart failure patients showed that the longer the contact of health professionals with the patient, the better the ef- fect on mortality and risk of hospitalization for heart fail- ure, although the cumulative effect was miniscule (roughly 1% decrease per month of intervention) with considerable heterogeneity between studies12.

Educational interventions may be stepwise. Yu et al. investigated the effect of a multi-step educational strategy on 160 hospitalized heart failure patients. At the begin- ning, patients were given an educational booklet regarding their disease, created in collaboration with nurses and other patients, so that barriers regarding health literacy were removed. Prior to discharge from hospital, their questions were answered by the investigator and patients were then contacted weekly for one month by telephone. In the event of deterioration, no telephone call was made but a doctor’s visit was recommended. The intervention group had significantly better adherence to medication measured by a validated questionnaire at 3-month follow- up13.

Counselling Apart from education about various disease aspects,

patient-centred interventions should include further coun- selling with a focus on a patients’ cognitive and psycholog-

Table 1. Division of interventions to improve medication adherence.

Patient-Centric Interventions Healthcare Provider Interventions System-Level Interventions

Education Training Policy changes Counselling Simplification of medication Care coordination Reminders Side-Effect Management Apps & Telehealth

Fig. 1. The complex structure of interventions to improve adherence to medication in heart failure patients.

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ical barriers. This may include the principles of cognitive behavioural therapy (CBT).

Cognitive function is a predictor of outcome in vari- ous chronic diseases including heart failure14. Using 149 patients, Alosco et al. found that cognitive function, as attention, executive, and language functions, was an in- dependent predictor of medication adherence in patients with heart failure15. Similarly, in a study of 87 left ventricle assist device (LVAD) patients, Casida et al. used question- naires to show that higher levels of cognitive function were positively correlated with adherence to LVAD meas- ures. This led to better quality of life indicators16.

Depression and other negative psychosocial factors impair medication adherence in heart failure17. One ef- fective intervention to reduce these barriers is CBT. In a meta-analysis of studies of the effect of CBT on heart failure patients, Jeyanatham et al. showed that it is an effective intervention for improving a patients’ quality of life. The effect lasts mainly during counselling and 3 months thereafter, the strength of the intervention then fades. However, the effect on hard data, mortality and hospital admissions was not statistically significant in the reviewed studies18.

In another study, Wu et al. counselled heart failure patients using the theory of planned behaviour (TPB). This is a theoretical model that allows prediction of how individuals will behave and then intervening in barriers to desirable behaviour19. The 82 patients in the study were divided into control and 2 intervention groups that were either only education about the disease and, lifestyle and treatment measures or TPB and adherence feedback measured. Adherence was measured using MEMS. Both intervention groups improved in terms of medication ad- herence and quality of life. The result also translated into longer event-free survival analysed using cox regression. The intervention was carried out by trained nurses and not doctors20.

Reminders A major barrier to adherence is the need to remember

every day to take the medication. Among ways of facilitat- ing adherence are various pillboxes, alarms or automated messaging systems. In chronic disease in general these measures appear to improve medication adherence21.

A study on 61 patients by Travis et al. used an elec- tronic pill box with a notification system to alert patients to take their medication. After a month of use, the authors report high adherence rate and patient satisfaction with the device22.

Apps and telehealth As part of telemedicine, m-health, defined by the

WHO as medical practice supported by mobile devices, is currently developing rapidly23. A small study by Goldstein et. al compared an mhealth app serving as either a pas- sive recorder or an active reminder with an electronic pillbox again either with an active alarm or in silent mode. Adherence was measured either by opening the pillbox or by electronic self-report by the patient. After 1 month of follow-up, there were no differences in adherence, which

was high, around 80%. Patients themselves preferred the m-health approach24.

Healthcare provider interventions Interventions targeting healthcare providers also lead

to better patient outcomes. To achieve clinical outcomes it is suggested that several such approaches should be combined25.

Training Training on how to better educate and motivate pa-

tients to adhere to their medication regimen ultimately leads to improved adherence. Although this approach is also effective, the main focus should still be on patient education. In general, patient-centred educational inter- ventions are more effective25. In the context of heart fail- ure, Ruppar et al. concluded in a large meta-analysis of interventions to improve heart failure management that healthcare provider training generally has less impact on patient mortality than other interventions studied9.

One way is to gradually change the approach of healthcare providers from solely disease education to a motivational approach26. It is advisable to invest enough time to explore the motional, psychological, and socioeco- nomic barriers of a particular patient and find solutions to them27. A study by Sana et al. on 240 hypertensive patients suggests that programs to improve health care professionals’ communication skills improve patients’ self- reported adherence to medication. Heart failure-specific randomized controlled trials have not yet been conducted to the best of our knowledge28.

Simplification of medication As the number of treatment options for chronic dis-

eases increases, so does the number of drugs that patients have to take. This increases the complexity of medication regimens. As the complexity of medication increases, the risk of medical error increases and the risk of hospitali- sation increases29. Medication adherence also decreases with increasing complexity of the drug regimen30. The solution is to simplify medication. This can be achieved either by reducing the number of individual tablets using single-pill combination therapy, by reducing the number of daily doses, or by a combination of these two mea- sures. A meta-analysis of 17 studies examining the above measures in patients with chronic diseases demonstrated their effectiveness in increasing adherence. However, in- creased adherence did not translate into improved clinical outcomes in these studies31.

Side-effect management A larger number of drugs also leads to a higher poten-

tial for drug interactions and associated higher number of side effects. Their impact can be reduced by patient educa- tion; patients who expect side effects may be better pre- pared for them and better adhere to the medication32. In a study by Jarab et al. of 427 heart failure patients, it was found that patients who did not suffer from medication side effects had significantly higher odds of having supe- rior levels of adherence, as measured by questionnaires33.

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One possible intervention for the management of typical side effects in heart failure is the use of more modern agents, e.g. replacing spironolactone with eplerenone34.

System-level interventions Policy changes

The third type of intervention targets the health sys- tem as a whole. A major barrier to improving cardiovascu- lar medication adherence in the vast majority of systems is the cost of medicines (and healthcare in general) for individual patients35. Although there is a consensus on the inverse relationship between medication cost and adherence, there are limited data on how strong this re- lationship is. The heterogeneity of health systems and vari- ability in prices and funding sources makes it difficult to compare studies between systems. The ethics of deciding for whom to reduce the cost if randomisation is used and how to blind such a design is also a significant barrier to study design. In 2010, Maciejewsky et al. published a large retrospective study looking at value-based insurance program design for patients with chronic diseases, includ- ing congestive heart failure. Over 1,200,000 patients in two arms, followed for 2 years, were included. Adherence was measured by medication possession ratio. The inter- vention consisted of reducing patient co-payments for medication. In the control group, adherence decreased significantly more at the end of the follow-up period, by 1.5–3.8%, depending on the disease and drug36.

Care coordination One of the most important prerequisites for good

patient care and a method for improving adherence to medication is coordination of care within a team of health professionals37. Care and treatment are now increasingly the domain not only of the physician, but also of nurses, pharmacists and other supporting professions. This is reflected in various studies and emphasized in one meta- nalysis of interventions by Unverzagt et al.37

Challenges and limitations in existing research A major challenge in the implementation of adherence

improvement interventions (especially patient-centric) is the need for long-term action and an individualized ap- proach to the patient in order to achieve a clinical effect37.

A common problem of research interpretation is the heterogeneity of existing studies. Intervention popula- tions differ in baseline clinical characteristics, length of follow-up and, most importantly, in adherence monitoring methods.

There is currently no gold standard of measurement. Although there is considerable popularity of the MEMS method and it is considered a standard by some authors.7 However, other authors refer to testing serum drug levels in the same way, but mainly in the context of hyperten- sion. Even so, it is the detection of adherence to the same drugs as in heart failure38,39.

CONCLUSION

With the increasing importance of heart failure within health systems, it is paramount to look for ways to make care more effective. One potentially promising option is to increase patient adherence to medication. Interventions to improve this factor vary according to the target of the intervention, whether it is aimed at the patient, the health- care provider, or the whole system, and the barriers to adherence it seeks to overcome. The complexity of heart failure and its treatment necessitates a multifaceted ap- proach that addresses various barriers to adherence si- multaneously.

Although the range of possible interventions is wide and variable, a few key points can be summarised. Studies show that longer engagement with healthcare profession- als correlates with improved outcomes. In general, strate- gies that focus on patient education are more effective than those that focus on health professionals. Further, the use of a team consisting of not only physicians but also other specialties such as pharmacists or nurses is particularly beneficial.

Future research should focus on long-term outcomes of these interventions, addressing the heterogeneity in study designs and adherence measurement methods.

Search Strategy and Selection Criteria Our research strategy was aimed at evaluating studies

on interventions to improve adherence and barriers to adherence in chronic heart failure. Data for this article were identified by search of PubMed database and refer- ences from relevant articles using the terms “adherence”, “compliance” “interventions” and “chronic heart failure”. All searches were up to date as of 1. 2. 2024. Only ar- ticles published in English were included, abstracts and reports from meetings were not included. We searched for publications in the last 15 years and gave preference to publications from the past 10 years.

Acknowledgement: We would like to thank Alexander Oulton Ph.D. (neurosciences) for professional English language revision and proof-reading. Author contributions: LJ: manuscript writing; JV, ML: supervision. Conflict of interest declaration: The authors declare that they have no affiliations with or involvement in any orga- nization or entity with any financial interest in the subject matter or materials discussed in this manuscript

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