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Adherence and perception of medication in patients with chronic heart failure during a five-year randomised trial
Patient Education and Counseling 61 (2006) 348–353 www.elsevier.com/locate/pateducou
Adherence and perception of medication in patients with chronic heart failure during a five-year randomised trial Inger Ekman a,*, Gull Andersson b, Kurt Boman c, Andrew Charlesworth d, John G.F. Cleland e, Philip Poole-Wilson f, Karl Swedberg g a
The Sahlgrenska Academy, Faculty of Health and Caring Sciences, Institute of Nursing, Go¨teborg University, Box 457, SE 405 30, Go¨teborg, Sweden b Scandinavian Clinical Research Institute (CRI), Go¨teborg, Sweden c Department of Medicine, Skelleftea˚ County Hospital, HeartNet, Skeria, Skelleftea˚ and Department of Public Health and Clinical Medicine, Umea˚ University, Sweden d Nottingham Clinical Research Group (NCRG), Nottingham, UK e University of Hull, Kingston upon Hull, UK f Cardiac Medicine, National Heart and Lung Institute, Faculty of Medicine, Imperial College, London, UK g ¨ stra, Go¨teborg, Sweden Department of Medicine, Sahlgrenska University Hospital/O Received 15 December 2004; received in revised form 13 April 2005; accepted 16 April 2005
Abstract Objective: Many patients with chronic heart failure (CHF) are thought to be non-adherent to their prescribed medications. The objective was to describe perceptions about and adherence to regular medicines and study medication at baseline and study end in CHF patients participating in a clinical trial. Methods: In the carvedilol or metoprolol European trial (COMET), patients (N = 3029) with CHF were randomised and followed during a 58-month period. Patients at some Swedish centres answered a questionnaire at baseline and study end concerning their perception of their regular heart medication and study medication. Adherence was established through estimation of drug usage. Results: In the Swedish sub-study, 302 patients responded once to the questionnaire while 107 patients responded both at baseline and at follow-up. At baseline, 94% of the patients stated that they believed that the study medication would make them feel better and 82% believed that their regular heart medication would do so. During the study, patients’ belief in their regular cardiac medication significantly increased. Lack of belief in medication at the start of the study was a strong predictor of withdrawal from the trial (64% versus 6.8%; p < 0.0001). Those patients with very poor well-being and limited functional ability (classified as NYHA III–IV) at baseline significantly ( p = 0.01) increased their belief in the regular cardiac medication but not in their study medication. Conclusion: Belief in medication may be related to how the patient experiences the medication’s impact on functional ability, symptoms and well-being. Practice implications: Early identification of patients’ beliefs about medication seem to be an important factor in counselling and information to patients with CHF. # 2005 Elsevier Ireland Ltd. All rights reserved. Keywords: Adherence; Patient education; Counselling; RCT; COMET
1. Introduction Chronic heart failure (CHF) is a disabling lifelong progressive condition, leading to incapacitating symptoms, * Corresponding author. Tel.: +46 31 7736014; fax: +46 31 7736050. E-mail address: [email protected] (I. Ekman).
frequent hospitalization and increased risk of death [1]. Because of an aging population and the improved survival after coronary events, such as myocardial infarction, CHF can be considered a significant health problem. Research in CHF has been successful in achieving pharmaco therapeutic advances in improving survival [1]. We have, however, fallen short in identifying the elements
0738-3991/$ – see front matter # 2005 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.pec.2005.04.005
I. Ekman et al. / Patient Education and Counseling 61 (2006) 348–353
necessary to facilitate clients/patients’ adherence to a complex medical regimen [2]. Research suggests that as many as 50% of medicines prescribed for the treatment of chronic conditions are not taken as they are prescribed [3]. Several studies have found that approximately 50–70% of CHF patients are adherent to 80% of the prescribed medication [4–6]. Adherence can be defined as attending to a specific health care regimen. Adherence is also referred to in the health care literature as ‘‘compliance’’ [3]. The concept of compliance, with its paternalistic associations of obedience, firmly places the onus on the patient. To avoid this association alternative terms like concordance and adherence has been proposed [7]. In the past three decades, researchers have studied patients’ behavior as it is related to health care recommendations, such as medicines, diet, exercise and other lifestyle changes. The majority of adherence research is theoretically derived from sociology and psychology, and emphasises the rationality of lay behavior focusing on the reasons why people do not take their medicine as prescribed, e.g., [8]. Non-adherence to clinicians’ prescriptions is thought to result in more frequent hospital admissions, and even premature death; an estimated 54% of CHF-related hospitalizations are thought to be preventable [9]. Factors known to be predictive of, or associated with, nonadherence to prescribed medication include demographic variables (e.g., age, gender and socio-economic status), medication characteristics (e.g., side effects and complexity of regimen) and psychosocial issues (e.g., social support and social participation and integration in society) [10]. Even where patients consider that they are adhering to treatment and self-care guidelines, many fail because of misconceptions in communication between patients and healthcare providers [11]. The caregiver’s objective risk assessment and the patient’s subjective risk perception are seldom identical. Attitudes, beliefs and perceptions of prescribed medication have been shown to be the strongest predictors of non-adherence [12]. Beliefs in medications include whether a medication is perceived as necessary for maintaining health [12]. In patients with CHF, the clinical implications of these factors include educating and counselling and continued monitoring over time. From the patient’s perspective, being involved in a clinical trial provides continuous access to physicians and nurses who can give information about the patient’s condition and the medicines, as well as mediate hopes concerning the efficacy of the new treatment [13,14]. The carvedilol or metoprolol European trial (COMET) was a large, international, randomised, controlled study on the effect of beta-blockers (carvedilol and metoprolol) in patients with CHF [15]. The present report focuses on a subset of Swedish patients who participated in the COMET trial. The objective of this study was to describe perceptions about and adherence to regular medicines and study medication at baseline and study end in a Swedish subgroup.
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2. Methods The design of the COMET trial has been reported previously [15]. The main inclusion criteria were the presence of chronic symptomatic New York Heart Association (NYHA) class II–IV heart failure, left ventricular ejection fraction 35%, at least one cardiovascular hospitalization during the previous 2 years, on stable heart failure treatment with ACE inhibitors for at least 4 weeks unless contraindicated and on treatment with diuretics (40 mg of furosemide or equivalent) for at least 2 weeks. Patients with unstable angina, myocardial infarction, coronary revascularization, stroke or symptomatic, sustained ventricular arrhythmia within the previous 2 months were excluded. The dose of study drug was increased to the target dose of carvedilol (25 mg bid) or metoprolol (50 mg bid) at weekly intervals. In addition to dose titration and dose adjustments (of study drug or regular medicines), which could be done at any time during the study (on average 58 months), patients were assessed every 4 months. At each assessment, patients were invited to report on a five-point scale the severity of their breathlessness, orthopnea, fatigue, angina and overall well-being. In addition, each patient’s NYHA class was recorded. The study nurses took care of the patients on each visit and provided continued support, answered questions and asked if the patients had noticed any other new sensation or symptom since the previous visit. By asking the patients to show their used bottles with the study drug, the nurses evaluated the degree of adherence to study medication on a three-level scale: good (>80% of the pills taken), moderate (60–80% taken) or poor (<60% taken). In order to find out patients’ perception regarding both their background medication and study medication, structured interviews were performed from the questionnaire, ‘‘Patients’ perception of regular medication and study medication’’. The questionnaire, which was developed and formulated by an experienced (15 years) study nurse (GA), contains three dimensions: adherence, knowledge and belief about medicines. The items were formulated from experiences of clinical trials as well as existing literature within the field. The questionnaire was first tested by study nurses, and after revising some of the items from this test, the questionnaire was re-tested by 20 patients involved in a clinical trial and thereafter no further changes were made. In Sweden, 37 centres participated in the COMET study. The study nurses at these centres were invited to participate in the study in the beginning of 1997. Of these 37 centres, 21 accepted to participate at baseline. Other centres entered during follow-up. Thus, at study end, a total of 32 centres were involved in the study. In this study, 302 patients answered the questionnaire only once and 107 of them completed the questionnaire twice. The interviews were performed at baseline (1997/1998) and at study end (November 2002).
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Table 1 Baseline characteristics Sub-study N = 302
Main study N = 2727
Total N = 3029
Age (years) mean/S.D. Gender (% male)
65.6/10.1 84.1
61.6/11.4 79.3
62.0/11.4 79.8
NYHA class % II % III % IV
53.6
47.8
48.4
44.7 1.7
48.1 4.0
47.8 3.8
Duration CHF (months) mean/median Previous MI (%) Hypertension (%) Diabetes (%) Stroke (%)
32.0 (15.0) 43.8 31.4 22.8 8.6
43.5 (22.0) 41.3 37.5 24.3 6.9
42.4 (21.0) 41.5 36.9 24.2 7.1
Concomitant medication at randomisation Diuretics (%) ACE Inhibitors (%) Angiotensin receptor antagonists (%) Digitalis (%) Antiarrhythmics (%) Nitrates (%) Aldosterone antagonists (%) Beta-blockers (%) Anticoagulants (%) Aspirin (%) Lipid lowering agents (statins) (%)
99.3 93.0 5.6 52.3 2.3 31.5 5.3 6.3 34.4 47.7 19.2
98.6 91.2 6.6 60.2 13.2 32.9 11.4 4.1 47.0 35.6 21.3
98.7 91.4 6.5 59.4 12.1 32.8 10.8 4.3 45.7 36.8 21.1
2.1. Statistics Continuous variables are summarized as mean S.D. and categorical data are presented as cell frequencies and percentages. The factors that affect compliance in the main study were assessed using ANOVA and chi-squared tests for continuous and categorical data, respectively. For both patient knowledge and belief in medications in the sub-study, differences between baseline and study end percentages were assessed using McNemar’s test. To examine patient belief in the heart and study medication, the patients were divided into three ‘‘belief’’ groups: belief in medications are now weaker, beliefs had stayed the same and beliefs are now stronger. The impact of other factors (e.g., symptoms) on these three groups was assessed using chi-squared tests.
Table 2 Length of time the patients had taken prescribed drugs at baseline Years
Patients N (%)
>5 1–5 <1
59 (38.3) 42 (27.3) 53 (34.4)
Total number of patients, 154.
107 patients who responded both at baseline and at followup and 302 patients who answered the questionnaire at least once. Mean age was 65.6 years and 84.1% of the patients were male. More detailed information about demographics is summarized in Table 1. About 40% of the patients at baseline had been taking prescribed drugs for more than 5 years and 34% less than a year; 40% of the patients took 6–12 pills per day. A majority of the patients consumed medication one to two times a day. Tables 2–4.
2.2. Ethics 3.1. Adherence in the main study The study conformed to good clinical practice guidelines and followed the recommendations of the Declaration of Helsinki. Written informed consent was obtained from all patients before enrolment. The protocol was approved by the local ethics research committees.
Mean percentage of the patients showing adherence (>80% of the medication taken) to the study medication Table 3 Number of pills taken per day at baseline Patients N (%)
3. Results The baseline characteristics in the Swedish subset did not differ significantly from those in the main study. There were
5 pills or less 6–12 pills 13 pills Total number of patients, 153.
86 (56.2) 61 (39.9) 6 (3.9)
I. Ekman et al. / Patient Education and Counseling 61 (2006) 348–353 Table 4 Number of times the medication was taken per day Times per day
Patients N (%)
1–2 3–4 5
130 (84.4) 21 (13.6) 3 (1.9)
Total number of patients, 154.
during the whole study period in the main study was 88.6%. Reports of non-adherence with the study drug in more than one visit were significantly higher in patients with orthopnea ( p = 0.010) and severe fatigue ( p = 0.005).
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with very poor well-being and in NYHA III–IV at baseline significantly ( p = 0.01) increased their belief in their regular cardiac medication but not in their study medication. The percentage of patients who believed the study medication would make them feel better was 94% at baseline and 92% at study end. A larger percentage of the patients who withdrew from the study medication did not believe they would feel better from the study drug compared with those patients who continued (64% versus 6.8%; p < 0.0001). Table 5 presents an overview of the patients’ answers at baseline and study end to the questionnaire.
3.2. Adherence in the sub-study 4. Discussion and conclusion The question, ‘‘do you sometimes forget to take your heart medication?’’ was answered in the affirmative by 24% of the patients at baseline and by 17% at study end. At baseline and at study end, 6 and 3% of the patients, respectively, reported that they had forgotten to take their regular heart medicine from one to five times per week. Patients were asked what they would do if they forget to take one dose of their heart medicine. The results indicated that 72% of the patients at baseline and 65% at study end answered that they would take the dose later, 22% would skip taking the dose at baseline and 32% would take the dose at study end. 3.3. Patients’ knowledge Patients’ knowledge concerning the names of the medicines (69% at baseline and 63% at study end) and how the medicines work (64% at baseline and 60% at study end) did not significantly increase during the course of the study. In addition, the patients’ awareness of the need to take the medication for the rest of their lives did not increase over time (16% at baseline and 13% at study end). 3.4. Patient beliefs in medication The number of patients who believed that their regular heart medication made them feel better increased from 82 to 93% from baseline to study end ( p = 0.03). Those patients
4.1. Discussion In the present study, we found high adherence (88.6%) to study medication during the whole study period of 58 months. Adherence to study medication in clinical trials has ranged from 40 to 90% in other studies [16]. Adherence to regular medication in chronic illness is seldom reported to be above 50% [3]. The main difference between clinical practice and a clinical trial in evaluating treatment is that in the context of a trial, patients regularly have contact with nurses and physicians who follow up the patient’s health problems and monitor the adherence to study medication. In treatment of CHF, COMET is the randomised trial that has thus far been performed over the longest period of time. Further, it is the only long-term (>2 years) controlled trial with beta-blockers in CHF, as all earlier studies have been prematurely closed because of beneficial effects on mortality. Therefore, patients were probably acquainted with the study nurses, which made it simpler for the patients to discuss their condition and treatment, leading to the high adherence rate in medication. In contrast to their belief in the study medication, in which severe symptoms of fatigue and orthopnea were significantly related to non-adherence, we found that patients with more severe symptoms increased their belief in the regular heart medication. This finding might be related to lack of improvement regarding symptoms, which motivated some of the patients to lose
Table 5 Patients’ answers to the questionnaire, comparing baseline with study end Item
Yes, baseline N (%)
Yes, study end N (%)
p-Value
Sometimes forget to take heart medication Forget to take from1-5 pills per week When forgotten, the medication is taken later When forgotten, the medication is skipped Know the names of the medicines Know how the medicines work Think they can stop taking the medicine in the future Believing that the regular heart medication will make him/her feel better Believing that the study medication will make him/her feel better
25 6 62 19 72 65 16 88 83
18 3 56 28 66 61 13 99 81
ns ns ns ns ns ns ns 0.0266 ns
Total number of patients, 107.
(23.8) (5.7) (72.1) (22.1) (68.5) (63.7) (16.0) (82.2) (94.3)
(17.1) (2.8) (65.1) (32.6) (62.9) (59.8) (13.0) (92.5) (92.1)
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their belief in the study medication. A recent synthesis of qualitative studies about adherence to medication found that the most common hope patients have in their medicines was related to relief or control of symptoms. Other patient desires concerned the avoidance of relapse and hospitalisation, disease progression to stop or at least slow down and the prevention of future illness [17]. Moreover, many of the patients in the present study who did not believe in their study medication withdrew from the study. It might have been this reason behind the facts presented by Butler et al. [18] in which 37% of the patients discharged with betablocker after a myocardial infarction did not refill their prescription after 6 months. Research has indicated that belief in medication is related to personal perceptions of the necessity of medication and concerns about adverse effects and the way in which each individual balances the perceived benefits against perceived risks [20]. In addition, perceived side effects are increasingly common reasons for nonadherence to guideline-directed regimens, e.g., [19]. In this study, 13% of the patients felt they would not need the medication in the future. This finding might be explained from research in which patients’ perceptions toward drug use have been examined. Several studies have found that respondents generally dislike drugs and thus make minimal use of them [12,20]. There seems to exist a deep suspicion toward drugs, and from this perspective, it is surprising that so many of the patients in this study still believed in their medicine. During more than 4 years of maintenance of the study, a relationship based on trust and mutual respect between the nurses, physicians and the patients seems to have been created, which may be the reason the patients believed in the treatment. Nurse-led heart failure programs have been shown to decrease CHF hospital readmissions and reduce mortality [21,22]. Although the components that lead to this effect are not yet clarified [2], one of them might be the nurses’ ability to assist patients in coping with their prescribed treatment. We know little today about how patients judge the benefit of their treatment or about the accuracy with which changes in symptoms are attributed to the beneficial or adverse effects of treatment. This is an important area for further research as mistaken attributions may lead to distress or inappropriate action such as non-adherence. There are several limitations of this study that should be noted. One limitation concerns how the rate of adherence has been evaluated. In this study, the patients showed their containers of medication and the contents were counted by the study nurse. A recent study found that electronic systems that record the date and time of opening the study medication container and patients’ self-reports were equally good measurements [9]. It would, however, have been beneficial if more measurements evaluating adherence had been used in the whole study population. Another important issue is that the population in the COMET trial consisted predominantly of men about 60 years old. In the clinical setting patients suffering from heart failure are generally older and adherence to medicines have been shown to be lower in women and
elderly patients [23]. Another limitation is that in the Swedish sub-study only 107 patients completed the questionnaire both at baseline and study end. This low response rate was not caused primarily by the patient’s lack of willingness to participate but because several centres were not prepared to participate in the sub-study at the start of the main study, and therefore, these centres did not include patients at baseline. 4.2. Conclusion Belief in medication and subsequent adherence to prescribed medication may be related to how patients experience the impact of medicines on functional ability, symptoms and well-being. 4.3. Practice implications Early identification of patient beliefs about medication should be considered an important component in counselling and information to patients with CHF. Instead of standardized patient education programs, the caregivers’ pedagogical strategies should be planned from each patient’s perceptions and beliefs of his or her condition and treatment.
References [1] Remme WJ, Swedberg K. Guidelines for the diagnosis and treatment of chronic heart failure. Eur Heart J 2001;22:1527–60. [2] Ekman I, Swedberg K. Home-based management of patients with chronic heart failure—focus on content not just form! Eur Heart J 2002;23:1323–5. [3] Haynes RB, McDonald HP, Garg AX, Montague P. Interventions for helping patients to follow prescriptions for medications. The Cochrane Database of systematic reviews, 2002, Article no. CD 000011. [4] McDonald HP, Garg AX, Haynes RB. Interventions to enhance patient adherence to medication prescriptions. J Am Med Assoc 2002;288: 2868–79. [5] Cline CMJ. Bjorck-Linne AK, Israelsson BYA. Willenheimer RB, Erhardt LR. Non-compliance and knowledge of prescribed medication in elderly patients with heart failure. Eur J Heart Fail 1999;1:145–9. [6] Bohachick P, Burke LE, Sereika S, Murali S, Dunbar-Jacob J. Adherence to angiotensin converting enzyme inhibitor therapy for heart failure. Prog Cardiovasc Nurs 2002;17:160–6. [7] From Compliance to Concordance: Towards Shared Goals in Medicine Taking. Report. London, Royal Pharmaceutical Society of Great Britain, 1997. [8] Rosenstock IM, Strecher VJ, Becker MH. Social learning theory and the Health Belief Model. Health Educ Q 1988;15:175–83. [9] Michalsen A, Konig G, Thimme W. Preventable causative factors leading to hospital admission with decompensated heart failure. Heart 1998;80:437–41. [10] Dunbar-Jacob J, Bohachick P, Mortimer MK, Sereika SM, Foley SM. Medication adherence in persons with cardiovascular disease. J Cardiovasc Nurs 2003;18:208–9. [11] Horowitz CR, Rein SB, Leventhal H. A story of maladies, misconceptions and mishaps: effective management of heart failure. Soc Sci Med 2004;58:631–43. [12] Horne R, Weinman J. Patients’ beliefs about prescribed medicines and their role in adherence to treatment in chronic physical illness. J Psychosom Res 1999;36:1138–61.
I. Ekman et al. / Patient Education and Counseling 61 (2006) 348–353 [13] Madsen SM, Holm S, Davidsen B, Munkholm P, Schlichting P, Riis P. Ethical aspects of clinical trials; the attitudes of participants in two non-cancer trials. J Int Med 2000;248:463–74. [14] Yuval R, Uziel K, Gordon N, Merdler A, Khader N, Karabi B, Flugelman MY, Halon DA, Lewis BS. Perceived benefit after participating in positive or negative/neutral heart failure trials: the patients’ perspective. Eur J Heart Fail 2001;3:217–23. [15] Poole-Wilson PA, Swedberg K, Cleland JGF. Di Lenarda A, Hanrath P, Komajda M, Lubsen J, Lutiger B, Metra M, Remme WJ, TorpPedersen C, Scherhag A, Skene A. The COMET investigators. Comparison of carvedilol and metoprolol on clinical outcomes in patients with chronic heart failure in the carvedilol or metoprolol European trial (comet): randomised controlled trial. Lancet 2003;362:7–13. [16] Hamilton GA. Measuring adherence in a hypertension clinical trial. Eur J Cardiovasc Nurs 2003;2:219–28. [17] Pound P, Britten N, Morgan M, Yardley L, Pope C, Daker-White G, Campbell R. Resisting medicines: a synthesis of qualitative studies of medicine taking. Soc Sci Med 2005;61:135–55.
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[18] Butler J, Arbogast PG, BeLue R, Daugherty J, Manoj KJ, Wayne AR, Griffin MR. Outpatient adherence to betablocker therapy after acute myocardial infarction. J Am Coll Cardiol 2002;40:1589–95. [19] Berman RS, Epstein RS, Lydick E. Risk factors associated with women’s compliance with estrogen replacement therapy. Women’s Health 1997;6:219–26. [20] Townsend A, Hunt K, Wyke S. Managing multiple morbidity in midlife: a qualitative study of attitudes to drug use. BMJ 2003;327:837. [21] Stewart S, Horowitz JD. Home-based intervention in congestive heart failure long term implications on readmission and survival. Circulation 2002;105:2861–6. [22] Stro¨mberg A, Ma˚rtensson J, Fridlund B, Levin LA, Karlsson JE, Dahlstro¨m U. Nurse-led heart failure clinics improve survival and selfcare behaviour in patients with heart failure: results from a prospective, randomised study. Eur Heart J 2003;24:1014–23. [23] van der Wal M, Jaarsma T, van Veldhuisen D. Non-compliance in patients with heart failure; how can we manage it? Eur J Heart Fail 2005;7:5–17.
Adherence and perception of medication in patients with chronic heart failure during a five-year randomised trial Inger Ekman a,*, Gull Andersson b, Kurt Boman c, Andrew Charlesworth d, John G.F. Cleland e, Philip Poole-Wilson f, Karl Swedberg g a
The Sahlgrenska Academy, Faculty of Health and Caring Sciences, Institute of Nursing, Go¨teborg University, Box 457, SE 405 30, Go¨teborg, Sweden b Scandinavian Clinical Research Institute (CRI), Go¨teborg, Sweden c Department of Medicine, Skelleftea˚ County Hospital, HeartNet, Skeria, Skelleftea˚ and Department of Public Health and Clinical Medicine, Umea˚ University, Sweden d Nottingham Clinical Research Group (NCRG), Nottingham, UK e University of Hull, Kingston upon Hull, UK f Cardiac Medicine, National Heart and Lung Institute, Faculty of Medicine, Imperial College, London, UK g ¨ stra, Go¨teborg, Sweden Department of Medicine, Sahlgrenska University Hospital/O Received 15 December 2004; received in revised form 13 April 2005; accepted 16 April 2005
Abstract Objective: Many patients with chronic heart failure (CHF) are thought to be non-adherent to their prescribed medications. The objective was to describe perceptions about and adherence to regular medicines and study medication at baseline and study end in CHF patients participating in a clinical trial. Methods: In the carvedilol or metoprolol European trial (COMET), patients (N = 3029) with CHF were randomised and followed during a 58-month period. Patients at some Swedish centres answered a questionnaire at baseline and study end concerning their perception of their regular heart medication and study medication. Adherence was established through estimation of drug usage. Results: In the Swedish sub-study, 302 patients responded once to the questionnaire while 107 patients responded both at baseline and at follow-up. At baseline, 94% of the patients stated that they believed that the study medication would make them feel better and 82% believed that their regular heart medication would do so. During the study, patients’ belief in their regular cardiac medication significantly increased. Lack of belief in medication at the start of the study was a strong predictor of withdrawal from the trial (64% versus 6.8%; p < 0.0001). Those patients with very poor well-being and limited functional ability (classified as NYHA III–IV) at baseline significantly ( p = 0.01) increased their belief in the regular cardiac medication but not in their study medication. Conclusion: Belief in medication may be related to how the patient experiences the medication’s impact on functional ability, symptoms and well-being. Practice implications: Early identification of patients’ beliefs about medication seem to be an important factor in counselling and information to patients with CHF. # 2005 Elsevier Ireland Ltd. All rights reserved. Keywords: Adherence; Patient education; Counselling; RCT; COMET
1. Introduction Chronic heart failure (CHF) is a disabling lifelong progressive condition, leading to incapacitating symptoms, * Corresponding author. Tel.: +46 31 7736014; fax: +46 31 7736050. E-mail address: [email protected] (I. Ekman).
frequent hospitalization and increased risk of death [1]. Because of an aging population and the improved survival after coronary events, such as myocardial infarction, CHF can be considered a significant health problem. Research in CHF has been successful in achieving pharmaco therapeutic advances in improving survival [1]. We have, however, fallen short in identifying the elements
0738-3991/$ – see front matter # 2005 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.pec.2005.04.005
I. Ekman et al. / Patient Education and Counseling 61 (2006) 348–353
necessary to facilitate clients/patients’ adherence to a complex medical regimen [2]. Research suggests that as many as 50% of medicines prescribed for the treatment of chronic conditions are not taken as they are prescribed [3]. Several studies have found that approximately 50–70% of CHF patients are adherent to 80% of the prescribed medication [4–6]. Adherence can be defined as attending to a specific health care regimen. Adherence is also referred to in the health care literature as ‘‘compliance’’ [3]. The concept of compliance, with its paternalistic associations of obedience, firmly places the onus on the patient. To avoid this association alternative terms like concordance and adherence has been proposed [7]. In the past three decades, researchers have studied patients’ behavior as it is related to health care recommendations, such as medicines, diet, exercise and other lifestyle changes. The majority of adherence research is theoretically derived from sociology and psychology, and emphasises the rationality of lay behavior focusing on the reasons why people do not take their medicine as prescribed, e.g., [8]. Non-adherence to clinicians’ prescriptions is thought to result in more frequent hospital admissions, and even premature death; an estimated 54% of CHF-related hospitalizations are thought to be preventable [9]. Factors known to be predictive of, or associated with, nonadherence to prescribed medication include demographic variables (e.g., age, gender and socio-economic status), medication characteristics (e.g., side effects and complexity of regimen) and psychosocial issues (e.g., social support and social participation and integration in society) [10]. Even where patients consider that they are adhering to treatment and self-care guidelines, many fail because of misconceptions in communication between patients and healthcare providers [11]. The caregiver’s objective risk assessment and the patient’s subjective risk perception are seldom identical. Attitudes, beliefs and perceptions of prescribed medication have been shown to be the strongest predictors of non-adherence [12]. Beliefs in medications include whether a medication is perceived as necessary for maintaining health [12]. In patients with CHF, the clinical implications of these factors include educating and counselling and continued monitoring over time. From the patient’s perspective, being involved in a clinical trial provides continuous access to physicians and nurses who can give information about the patient’s condition and the medicines, as well as mediate hopes concerning the efficacy of the new treatment [13,14]. The carvedilol or metoprolol European trial (COMET) was a large, international, randomised, controlled study on the effect of beta-blockers (carvedilol and metoprolol) in patients with CHF [15]. The present report focuses on a subset of Swedish patients who participated in the COMET trial. The objective of this study was to describe perceptions about and adherence to regular medicines and study medication at baseline and study end in a Swedish subgroup.
349
2. Methods The design of the COMET trial has been reported previously [15]. The main inclusion criteria were the presence of chronic symptomatic New York Heart Association (NYHA) class II–IV heart failure, left ventricular ejection fraction 35%, at least one cardiovascular hospitalization during the previous 2 years, on stable heart failure treatment with ACE inhibitors for at least 4 weeks unless contraindicated and on treatment with diuretics (40 mg of furosemide or equivalent) for at least 2 weeks. Patients with unstable angina, myocardial infarction, coronary revascularization, stroke or symptomatic, sustained ventricular arrhythmia within the previous 2 months were excluded. The dose of study drug was increased to the target dose of carvedilol (25 mg bid) or metoprolol (50 mg bid) at weekly intervals. In addition to dose titration and dose adjustments (of study drug or regular medicines), which could be done at any time during the study (on average 58 months), patients were assessed every 4 months. At each assessment, patients were invited to report on a five-point scale the severity of their breathlessness, orthopnea, fatigue, angina and overall well-being. In addition, each patient’s NYHA class was recorded. The study nurses took care of the patients on each visit and provided continued support, answered questions and asked if the patients had noticed any other new sensation or symptom since the previous visit. By asking the patients to show their used bottles with the study drug, the nurses evaluated the degree of adherence to study medication on a three-level scale: good (>80% of the pills taken), moderate (60–80% taken) or poor (<60% taken). In order to find out patients’ perception regarding both their background medication and study medication, structured interviews were performed from the questionnaire, ‘‘Patients’ perception of regular medication and study medication’’. The questionnaire, which was developed and formulated by an experienced (15 years) study nurse (GA), contains three dimensions: adherence, knowledge and belief about medicines. The items were formulated from experiences of clinical trials as well as existing literature within the field. The questionnaire was first tested by study nurses, and after revising some of the items from this test, the questionnaire was re-tested by 20 patients involved in a clinical trial and thereafter no further changes were made. In Sweden, 37 centres participated in the COMET study. The study nurses at these centres were invited to participate in the study in the beginning of 1997. Of these 37 centres, 21 accepted to participate at baseline. Other centres entered during follow-up. Thus, at study end, a total of 32 centres were involved in the study. In this study, 302 patients answered the questionnaire only once and 107 of them completed the questionnaire twice. The interviews were performed at baseline (1997/1998) and at study end (November 2002).
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Table 1 Baseline characteristics Sub-study N = 302
Main study N = 2727
Total N = 3029
Age (years) mean/S.D. Gender (% male)
65.6/10.1 84.1
61.6/11.4 79.3
62.0/11.4 79.8
NYHA class % II % III % IV
53.6
47.8
48.4
44.7 1.7
48.1 4.0
47.8 3.8
Duration CHF (months) mean/median Previous MI (%) Hypertension (%) Diabetes (%) Stroke (%)
32.0 (15.0) 43.8 31.4 22.8 8.6
43.5 (22.0) 41.3 37.5 24.3 6.9
42.4 (21.0) 41.5 36.9 24.2 7.1
Concomitant medication at randomisation Diuretics (%) ACE Inhibitors (%) Angiotensin receptor antagonists (%) Digitalis (%) Antiarrhythmics (%) Nitrates (%) Aldosterone antagonists (%) Beta-blockers (%) Anticoagulants (%) Aspirin (%) Lipid lowering agents (statins) (%)
99.3 93.0 5.6 52.3 2.3 31.5 5.3 6.3 34.4 47.7 19.2
98.6 91.2 6.6 60.2 13.2 32.9 11.4 4.1 47.0 35.6 21.3
98.7 91.4 6.5 59.4 12.1 32.8 10.8 4.3 45.7 36.8 21.1
2.1. Statistics Continuous variables are summarized as mean S.D. and categorical data are presented as cell frequencies and percentages. The factors that affect compliance in the main study were assessed using ANOVA and chi-squared tests for continuous and categorical data, respectively. For both patient knowledge and belief in medications in the sub-study, differences between baseline and study end percentages were assessed using McNemar’s test. To examine patient belief in the heart and study medication, the patients were divided into three ‘‘belief’’ groups: belief in medications are now weaker, beliefs had stayed the same and beliefs are now stronger. The impact of other factors (e.g., symptoms) on these three groups was assessed using chi-squared tests.
Table 2 Length of time the patients had taken prescribed drugs at baseline Years
Patients N (%)
>5 1–5 <1
59 (38.3) 42 (27.3) 53 (34.4)
Total number of patients, 154.
107 patients who responded both at baseline and at followup and 302 patients who answered the questionnaire at least once. Mean age was 65.6 years and 84.1% of the patients were male. More detailed information about demographics is summarized in Table 1. About 40% of the patients at baseline had been taking prescribed drugs for more than 5 years and 34% less than a year; 40% of the patients took 6–12 pills per day. A majority of the patients consumed medication one to two times a day. Tables 2–4.
2.2. Ethics 3.1. Adherence in the main study The study conformed to good clinical practice guidelines and followed the recommendations of the Declaration of Helsinki. Written informed consent was obtained from all patients before enrolment. The protocol was approved by the local ethics research committees.
Mean percentage of the patients showing adherence (>80% of the medication taken) to the study medication Table 3 Number of pills taken per day at baseline Patients N (%)
3. Results The baseline characteristics in the Swedish subset did not differ significantly from those in the main study. There were
5 pills or less 6–12 pills 13 pills Total number of patients, 153.
86 (56.2) 61 (39.9) 6 (3.9)
I. Ekman et al. / Patient Education and Counseling 61 (2006) 348–353 Table 4 Number of times the medication was taken per day Times per day
Patients N (%)
1–2 3–4 5
130 (84.4) 21 (13.6) 3 (1.9)
Total number of patients, 154.
during the whole study period in the main study was 88.6%. Reports of non-adherence with the study drug in more than one visit were significantly higher in patients with orthopnea ( p = 0.010) and severe fatigue ( p = 0.005).
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with very poor well-being and in NYHA III–IV at baseline significantly ( p = 0.01) increased their belief in their regular cardiac medication but not in their study medication. The percentage of patients who believed the study medication would make them feel better was 94% at baseline and 92% at study end. A larger percentage of the patients who withdrew from the study medication did not believe they would feel better from the study drug compared with those patients who continued (64% versus 6.8%; p < 0.0001). Table 5 presents an overview of the patients’ answers at baseline and study end to the questionnaire.
3.2. Adherence in the sub-study 4. Discussion and conclusion The question, ‘‘do you sometimes forget to take your heart medication?’’ was answered in the affirmative by 24% of the patients at baseline and by 17% at study end. At baseline and at study end, 6 and 3% of the patients, respectively, reported that they had forgotten to take their regular heart medicine from one to five times per week. Patients were asked what they would do if they forget to take one dose of their heart medicine. The results indicated that 72% of the patients at baseline and 65% at study end answered that they would take the dose later, 22% would skip taking the dose at baseline and 32% would take the dose at study end. 3.3. Patients’ knowledge Patients’ knowledge concerning the names of the medicines (69% at baseline and 63% at study end) and how the medicines work (64% at baseline and 60% at study end) did not significantly increase during the course of the study. In addition, the patients’ awareness of the need to take the medication for the rest of their lives did not increase over time (16% at baseline and 13% at study end). 3.4. Patient beliefs in medication The number of patients who believed that their regular heart medication made them feel better increased from 82 to 93% from baseline to study end ( p = 0.03). Those patients
4.1. Discussion In the present study, we found high adherence (88.6%) to study medication during the whole study period of 58 months. Adherence to study medication in clinical trials has ranged from 40 to 90% in other studies [16]. Adherence to regular medication in chronic illness is seldom reported to be above 50% [3]. The main difference between clinical practice and a clinical trial in evaluating treatment is that in the context of a trial, patients regularly have contact with nurses and physicians who follow up the patient’s health problems and monitor the adherence to study medication. In treatment of CHF, COMET is the randomised trial that has thus far been performed over the longest period of time. Further, it is the only long-term (>2 years) controlled trial with beta-blockers in CHF, as all earlier studies have been prematurely closed because of beneficial effects on mortality. Therefore, patients were probably acquainted with the study nurses, which made it simpler for the patients to discuss their condition and treatment, leading to the high adherence rate in medication. In contrast to their belief in the study medication, in which severe symptoms of fatigue and orthopnea were significantly related to non-adherence, we found that patients with more severe symptoms increased their belief in the regular heart medication. This finding might be related to lack of improvement regarding symptoms, which motivated some of the patients to lose
Table 5 Patients’ answers to the questionnaire, comparing baseline with study end Item
Yes, baseline N (%)
Yes, study end N (%)
p-Value
Sometimes forget to take heart medication Forget to take from1-5 pills per week When forgotten, the medication is taken later When forgotten, the medication is skipped Know the names of the medicines Know how the medicines work Think they can stop taking the medicine in the future Believing that the regular heart medication will make him/her feel better Believing that the study medication will make him/her feel better
25 6 62 19 72 65 16 88 83
18 3 56 28 66 61 13 99 81
ns ns ns ns ns ns ns 0.0266 ns
Total number of patients, 107.
(23.8) (5.7) (72.1) (22.1) (68.5) (63.7) (16.0) (82.2) (94.3)
(17.1) (2.8) (65.1) (32.6) (62.9) (59.8) (13.0) (92.5) (92.1)
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their belief in the study medication. A recent synthesis of qualitative studies about adherence to medication found that the most common hope patients have in their medicines was related to relief or control of symptoms. Other patient desires concerned the avoidance of relapse and hospitalisation, disease progression to stop or at least slow down and the prevention of future illness [17]. Moreover, many of the patients in the present study who did not believe in their study medication withdrew from the study. It might have been this reason behind the facts presented by Butler et al. [18] in which 37% of the patients discharged with betablocker after a myocardial infarction did not refill their prescription after 6 months. Research has indicated that belief in medication is related to personal perceptions of the necessity of medication and concerns about adverse effects and the way in which each individual balances the perceived benefits against perceived risks [20]. In addition, perceived side effects are increasingly common reasons for nonadherence to guideline-directed regimens, e.g., [19]. In this study, 13% of the patients felt they would not need the medication in the future. This finding might be explained from research in which patients’ perceptions toward drug use have been examined. Several studies have found that respondents generally dislike drugs and thus make minimal use of them [12,20]. There seems to exist a deep suspicion toward drugs, and from this perspective, it is surprising that so many of the patients in this study still believed in their medicine. During more than 4 years of maintenance of the study, a relationship based on trust and mutual respect between the nurses, physicians and the patients seems to have been created, which may be the reason the patients believed in the treatment. Nurse-led heart failure programs have been shown to decrease CHF hospital readmissions and reduce mortality [21,22]. Although the components that lead to this effect are not yet clarified [2], one of them might be the nurses’ ability to assist patients in coping with their prescribed treatment. We know little today about how patients judge the benefit of their treatment or about the accuracy with which changes in symptoms are attributed to the beneficial or adverse effects of treatment. This is an important area for further research as mistaken attributions may lead to distress or inappropriate action such as non-adherence. There are several limitations of this study that should be noted. One limitation concerns how the rate of adherence has been evaluated. In this study, the patients showed their containers of medication and the contents were counted by the study nurse. A recent study found that electronic systems that record the date and time of opening the study medication container and patients’ self-reports were equally good measurements [9]. It would, however, have been beneficial if more measurements evaluating adherence had been used in the whole study population. Another important issue is that the population in the COMET trial consisted predominantly of men about 60 years old. In the clinical setting patients suffering from heart failure are generally older and adherence to medicines have been shown to be lower in women and
elderly patients [23]. Another limitation is that in the Swedish sub-study only 107 patients completed the questionnaire both at baseline and study end. This low response rate was not caused primarily by the patient’s lack of willingness to participate but because several centres were not prepared to participate in the sub-study at the start of the main study, and therefore, these centres did not include patients at baseline. 4.2. Conclusion Belief in medication and subsequent adherence to prescribed medication may be related to how patients experience the impact of medicines on functional ability, symptoms and well-being. 4.3. Practice implications Early identification of patient beliefs about medication should be considered an important component in counselling and information to patients with CHF. Instead of standardized patient education programs, the caregivers’ pedagogical strategies should be planned from each patient’s perceptions and beliefs of his or her condition and treatment.
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