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REVIEW PAPER
Cardiovascular medication adherence among patients with cardiac
disease: a systematic review
Ali Hussein Al-Ganmi, Lin Perry, Leila Gholizadeh & Abdulellah Modhi Alotaibi
Accepted for publication 2 June 2016
Correspondence to A.H. Al-Ganmi:
e-mails: alihalek@yahoo.com or
ali.h.al-ganmi@student.uts.edu.au
Ali Hussein Al-Ganmi BSc MSc RN
PhD Candidate
University of Technology Sydney, Faculty of
Nursing, Midwifery and Health, Sydney,
New South Wales, Australia and
Assistant Lecturer
University of Baghdad, College of Nursing,
Iraq
Lin Perry MSc PhD RN
Professor/Core Member
University of Technology Sydney, Faculty of
Nursing, Midwifery and Health, Sydney,
New South Wales, Australia and
Health Services and Practice Research
Strength, South Eastern Sydney Local
Health District, Randwick, New South
Wales, Australia and
Prince of Wales Hospital, Randwick, New
South Wales, Australia
Leila Gholizadeh BSc Msc PhD RN
Lecturer/Associate Member/Core Member/
Doctor of Philosophy Member
Faculty University of Technology Sydney,
Faculty of Nursing, Midwifery and Health,
Sydney, New South Wales, Australia
Abdulellah Modhi Alotaibi MSc RN
PhD Candidate
University of Technology Sydney, Faculty of
Nursing, Midwifery and Health, Sydney,
New South Wales, Australia and
Lecturer
Shqra University, Faculty of Applied Health
Sciences, Saudi Arabia
AL-GANMI A.H., PERRY L., GHOLIZADEH L. & ALOTAIBI A.M. (2016) Car-
diovascular medication adherence among patients with cardiac disease: a systematic
review. Journal of Advanced Nursing 72(12), 3001–3014. doi: 10.1111/jan.13062
Abstract
Aims. The aim of this study was to critically appraise and synthesize the best
available evidence on the effectiveness of interventions suitable for delivery by nurses,
designed to enhance cardiac patients’ adherence to their prescribed medications.
Background. Cardiac medications have statistically significant health benefits for
patients with heart disease, but patients’ adherence to prescribed medications
remains suboptimal.
Design. A systematic quantitative review of intervention effects.
Data Sources. We conducted systematic searches for English-language, peer-
reviewed randomized controlled trial publications via Medline, EMBASE,
CINAHL, the Cochrane Library, ProQuest, Web of Science and Google Scholar
published between January 2004–December 2014.
Review methods. According to pre-determined inclusion and exclusion criteria,
eligible studies were identified and data extracted using a predefined form. Of 1962
identified papers; 14 studies met the study inclusion criteria, were assessed for risk
of bias using the Cochrane Collaboration tool; and included in the review.
Results. Study findings were presented descriptively; due to the heterogeneity of
studies meta-analysis was not possible. Included papers described interventions
categorized as: (1) multifaceted; and (2) behavioural and educational, comprising:
(a) text message and mail message; (b) telephone calls; (c) motivational
interviewing and (d) nurse-led counselling and education.
Conclusions. Substantial heterogeneity limited the robustness of conclusions, but
this review indicated that motivational interviewing, education and phone or text
messaging appeared promising as means to enhance cardiac medication
adherence. Future research should integrate multifaceted interventions that target
individual behaviour change to enhance adherence to cardiovascular medications,
to build on the beneficial outcomes indicated by this review.
Keywords: adherence, cardiac disease, cardiovascular medication, education, mo-
tivational interviewing, nurse-led intervention, nursing, systematic review, text
message
©2016 John Wiley & Sons Ltd 3001
Introduction
Medication non-adherence is a complex problem that poses
an enormous health and economic burden. It is more com-
mon among older age population and patients who need
multiple medications for their chronic conditions (Menditto
et al. 2015). It has been estimated that inadequate adher-
ence to treatment among patients with chronic diseases
affects up to 50% of patients (Lee et al. 2006, Wilke et al.
2011). Non-adherence is a multifactorial phenomenon,
affected by socio-economic status, health systems, disease
states, pharmacological therapies and patient beliefs (Sabat
e
2003). Supporting long-term adherence to medicines is an
essential component of patient management and requires
effective interventions to help achieve sustained medication
taking. This systematic review therefore aimed to identify
effective interventions used by nurses to improve cardiac
patients’ adherence to cardiac medications.
Background
Cardiovascular disease (CVD) remains the leading cause of
mortality among men and women and is responsible for
one-third of all deaths worldwide (World Health Organisa-
tion 2004). In developing countries, coronary heart disease
(CHD) accounts for more than 45 million deaths per
annum (Okrainec et al. 2004). Similar to international
trends, CVD is the single greatest cause of death in Aus-
tralia, accounting for the deaths of 11,733 males and 9780
females in 2011 (Australian Institute of Health and Welfare
2014). Although CHD is incurable, disease progress can be
significantly slowed by cardio-protective medicines and life-
style changes. Cardio-protective medicines are the primary
therapy for CHD, but adherence to these medications is
suboptimal, resulting in insufficient control of disease symp-
toms and increased risk of future cardiovascular events,
rehospitalization and death (Baroletti & Dell’Orfano 2010).
The World Health Organisation define adherence as ‘the
extent to which a person’s behaviour (taking medications,
following a recommended diet and/or executing lifestyle
changes) corresponds with the agreed recommendations of
a healthcare provider’ (Sabat
e 2003). Adherence to medica-
tion recommendations is necessary to receive the full bene-
fits of the medications. Medication non-adherence has been
defined as ‘taking less than 80% of prescribed doses and
can also include taking too many doses’ and it is associated
with an increased risk of poor health, adverse clinical
events and death (Nieuwlaat et al. 2014). It is estimated
that up to 50% of patients with CHD in high income coun-
tries do not take their medications as prescribed (Laba
et al. 2013). Poor medication adherence has been linked to
recurrent cardiac events and adverse patient outcomes
(Poluzzi et al. 2011, Nieuwlaat et al. 2014).
The prevalence of patients in the ageing Australian popu-
lation who are non-adherent to cardiovascular medications
has been reported to range from 14% to 43%, posing a
serious barrier to secondary prevention (McKenzie et al.
2015). Thus, long-term medication adherence in Australia
remains unsatisfactory, with the situation changing only
very slowly (Simons et al. 2011). Poor medication adher-
ence rates undermine the translation of the benefits of
Why is this research or review needed?
•Non-adherence to cardiovascular medicines is associated
with greater risk of hospitalization and mortality.
•Various studies examine the effectiveness of medication
adherence interventions, but the evidence is inconsistent
and unclear.
•Nurses play a key role in educating and supporting patients
with their medication, but evidence is lacking for effective
nurse-delivered interventions to promote medication adher-
ence for cardiac patients.
What are the key findings?
•Multifaceted interventions that target individual behaviour
change appear to offer most promising methods to enhance
adherence to cardiovascular medications.
•Current evidence indicates that the components for multi-
faceted interventions most likely to sustain adherence to
cardiac medication taking include motivational interview-
ing, education and phone or text messaging.
How should the findings be used to influence policy/
practice/research?
•Findings provide evidence to support clinicians’ choice of
interventions designed to enhance medication adherence
among patients with cardiac disease delivered by nurses.
•Rigorous methods are required for future studies to test the
effectiveness of nurse-led adherence interventions, taking
into account study design, sampling, choice of effective and
feasible adherence measures, ways to accommodate inter-
ventions in routine daily practice and longer term sustain-
ability of outcomes.
•Policy-makers should consider the opportunities offered by
nurse-led medication adherence interventions, to enhance
the contribution of nurses and thereby optimize the benefits
to patients of their prescribed medications.
3002 ©2016 John Wiley & Sons Ltd
A.H. Al-Ganmi et al.
well-established evidence-based cardiovascular medicines
into practice, reducing the effectiveness of secondary pre-
vention therapies (Haynes et al. 2005). It is crucial that
adherence to cardiovascular medicines is optimized to
improve disease symptoms and prevent the onset of further
serious cardiac events (van Dalem et al. 2012).
The effectiveness of a wide variety of interventions
intended to enhance medication adherence in patients with
CHD has been trialled. Several diverse and complex beha-
vioural, educational and combined intervention approaches
and outcomes measures have emerged; however, the effec-
tiveness of these interventions needs to be carefully evalu-
ated due to the diverse methodologies used in the studies. It
is important that healthcare professionals are aware of
effective practical strategies and have the necessary skills to
translate these interventions to outpatient healthcare set-
tings. The purpose of this systematic review was to identify
and synthesize the best available evidence on the effective-
ness of interventions within the nursing scope of practice,
designed to enhance cardiac patients’ adherence to cardio-
protective medications.
The review
Aims
Many and varied approaches have been trialled with the
intention of enhancing medication adherence, but what
interventions suitable for delivery by nurses are effective at
improving the adherence of cardiac patients to their pre-
scribed cardio-protective medications?
Design
A systematic quantitative review of intervention effects was
conducted according to the principles and processes of the
Cochrane Handbook for Systematic Reviews of Interven-
tions (Higgins & Green 2008). GRADE was used for grad-
ing the quality of evidence provided by findings (EPOC
Resources for review authors 2013). The PRISMA state-
ment (Moher et al. 2009) was used to guide reporting of
the review.
Search methods
A systematic literature search was conducted using six elec-
tronic databases: Medline, EMBASE, CINAHL, the
Cochrane Library, ProQuest and Web of Science. These
databases and Google Scholar were searched for articles
published in English between January 2004 - December
2014. The reference lists of all selected articles including
review articles were searched for additional studies. The
keywords used in the search strategy were based on the
‘PICOS’ framework (Table 1).
Studies were included if they were primary research
reported the results of unconfounded evaluation of inter-
ventions suitable for delivery by nurses to increase medica-
tion adherence for patients with CHD. The following
inclusion criteria were applied:
1) Study design was a RCT, clinical trial or controlled clini-
cal trial that examined the effectiveness of an interven-
tion to increase adherence to medications among patient
with cardiac disease, used for secondary prevention or
treatment of cardiac disease, where an intervention
group was compared with a control group who received
standard care or a clearly justified comparison group;
Table 1 PICOS framework for review criteria.
Criteria (PICOS) Keywords
Population (P) Cardiovascular disease*or Coronary
Artery Disease*or Coronary Heart
Disease*or Acute Coronary Syndrome
or Myocardial infarct*or Myocard*
Isch*or unstable Angina or Myocard*
or cardiac*or Cardiac patients or
Blood pressure.
Intervention (I) Behavio*change intervention or
behavioural change or nursing
intervention or behavio*(change,
enhance*, reinforce) or counselling or
medication (educat*, counsel*,
intervene*) or nurse-led intervention or
nurse-led or nurse councel*or
motivational interview or self-
management or self-efficacy or cardiac
treatment (statin*, antiplatelat*,
aspirin, antilipid, b-blockers, blood
pressure (BP) medication).
Control or
comparison (C)
A separate group who received standard
care or a clearly justified comparison
(no specific keywords)
Outcome (O) Medication adherence (increase*,
enhance*, improve*, intensify*,
reinforc*, promot*) or treatment
adherence or medication compliance or
medication concordance.
Study type (S) Randomized Controlled Trial (RCT) or
clinical trial or controlled clinical trial
or random allocation or double-blinded
method or single-blinded method or
(random$ and placebo$).
©2016 John Wiley & Sons Ltd 3003
JAN: REVIEW PAPER Medication adherence interventions for patients with cardiac disease
2) The population of interest comprised male and female
adults (≥18 years old) with a diagnosis of a cardiac
disease;
3) The intervention strategy was suitable (within the scope
of practice) for delivery by nurses and had either a pri-
mary or secondary aim to increase the adherence to med-
ication of patient with cardiac disease;
4) Patients were followed up for at least 6 months;
5) Medication was self-administered, that is, was not admin-
istered by a healthcare professional or carer and measured
by any method e.g.: pill count, electronic monitoring, refill
or prescription records or self-reported data.
Studies were excluded if they targeted patients with heart
valve disease or postcardiac surgeries; were written in a lan-
guage other than English; included non-cardiac disease
patients; tested interventions that required delivery by a
non-nursing healthcare professional, e.g. pharmacist; were
conducted in inpatient settings; and had less than 6 months
follow-up, because cardiovascular medications typically
require long-term adherence.
Search outcome
In total, search strategies identified 1962 citations of poten-
tial relevance. Initial screening of study titles and abstracts
revealed that more than 95% of the retrieved studies did
not meet the review inclusion criteria, leaving 94 papers for
further evaluation. The full texts of these papers were then
reviewed and 14 studies were retained for assessment. The
flow of studies through the selection process is summarized
in Figure 1.
Quality appraisal
The quality of included studies was appraised by three
authors (AA, LP & LG). Risk of bias assessment is pre-
sented in the supplementary online Table S1 using the
Cochrane Collaboration tool for assessing the risk of bias
(Higgins et al. 2011). Risk of bias was assessed indepen-
dently by the authors and discrepancies were resolved by
discussion (Figure 2).
Data abstraction
Data were extracted and analysed by three authors (AA, LP
& LG) using a predefined form. After quality appraisal of
these studies, 14 were retained for the review. Details of
data extracted are available in the supplementary online
Table S1.
Synthesis
Multiple sources of heterogeneity (interventions, adherence
measures and outcomes) were observed across the included
studies; formal meta-analysis was therefore not appropriate.
The heterogeneity was explored qualitatively by comparing
the characteristics of included studies. Studies were grouped
according to the main components of the interventions (see
the supplementary online Table S2).
Results
These fourteen included studies contained data on 4,548
patients with cardiac disease. These studies were summa-
rized based on the country of origin, participants’ cardiac
disease diagnostic group and the practice setting of inter-
ventions (Table 2). None of these studies detailed or con-
sidered the potential effect of socio-demographical, literacy
or economic characteristics on intervention outcomes. The
median follow-up time was 1 year, ranging from 6 months
to 24 months. Most studies achieved their endpoint out-
comes at 3-9 months. Interventions varied, with single,
combined and multifaceted component parts. Interventions
and study characteristics are detailed in Table S2.
Risk of bias assessment
Risk of bias was assessed using the Cochrane Collaboration
tool (Higgins et al. 2011) for selection, performance, attri-
tion, detection, reporting and systematic bias. All trials pro-
vided information about adequate sequence generation, 10
studies described the measures used to blind outcome asses-
sors from group allocation. Four studies avoided perfor-
mance bias (Jiang et al. 2007, Ogedegbe et al. 2008, Beune
et al. 2014, Leiva et al. 2014) by providing information
about adequate blinding of participants and personal. Ten
studies reported participants lost to follow-up; six trials pro-
vided study protocols and reported the methods of outcomes
assessment (medication adherence). The remaining studies
reported all outcomes but without study protocols (Schroeder
et al. 2005, Jiang et al. 2007, Ogedegbe et al. 2008, Smith
et al. 2008, Guirado et al. 2011, Kripalani et al. 2012,
Rinfret et al. 2013, Leiva et al. 2014) (Figure 2).
GRADE was used to rate the quality of evidence for
medication adherence. Scores ranged 1or+1 and were
summed to produce overall scores (4 =high, 3 =moderate,
2=low and 1 =very low) based on the risk of bias, design,
inconsistency, indirectness and imprecision in their scores
(EPOC Resources for review authors 2013). Most studies
were at low or unclear risk of bias and the quality of
3004 ©2016 John Wiley & Sons Ltd
A.H. Al-Ganmi et al.
evidence was rated moderate for the outcomes (Figure 2).
Hence, study results should be interpreted with caution.
Medication adherence measurement
Methods for measuring and monitoring medication regimen
adherence varied in these trials. Six studies each measured
adherence by self-report (Jiang et al. 2007, Guirado et al.
2011, Hacihasano
glu & Go€
ozu€
om 2011, Nieuwkerk et al.
2012, Beune et al. 2014, Ma et al. 2014) and by pharmacy
refill electronic data (Smith et al. 2008, Rinfret et al. 2013,
Ho et al. 2014, Leiva et al. 2014, Wald et al. 2014). The
Medication Event Monitoring System (MEMS) pill bottle
caps was used in one study (Schroeder et al. 2005) and two
studies applied both self-report and MEMS (Ogedegbe
et al. 2008, Kripalani et al. 2012).
Records identified through
database searching
(n = 1960)
Screening
Included Eligibility Identification
Records after duplicates removed
(n = 1945)
Records screened for title and
abstract
(n =1945)
Records excluded
(n = 1851)
Full-text articles assessed for
eligibility
(n = 94)
Full-text articles excluded,
with reasons
(n = 80)
17— Study design
11— Wrong participants
23— Different interventions &
providers
3— Follow-up for < 6 months
1— No adherence measurement
1— Medications not self-
administered
24— Reviews
Studies included for analysis
(n = 14)
Additional records identified from
references lists
(n = 2)
Figure 1 PRISMA flow diagram.
©2016 John Wiley & Sons Ltd 3005
JAN: REVIEW PAPER Medication adherence interventions for patients with cardiac disease
Types of intervention
Interventions were categorized according to their prominent
components and included: (1) multifaceted; and (2) beha-
vioural and educational interventions. The latter comprised:
(a) text message and mail message; (b) telephone calls; (c)
motivational interviewing; and (d) nurse-led counselling
and education. The complex nature of some interventions
made them difficult to categorize, but this was based on the
main component of intervention. Three studies examined
text message (TM) and/or mail message interventions
(Smith et al. 2008, Kripalani et al. 2012, Wald et al.
2014); two studies tested multifaceted intervention strate-
gies (Ho et al. 2014, Leiva et al. 2014); two studies investi-
gated the effect of structured telephone calls
(Hacihasano
glu & Go€
ozu€
om 2011, Rinfret et al. 2013) and
two studies used the motivational interviewing approach
(Ogedegbe et al. 2008, Ma et al. 2014). Five interventions
were classified as nurse-led counselling and education
(Schroeder et al. 2005, Jiang et al. 2007, Guirado et al.
2011, Nieuwkerk et al. 2012, Beune et al. 2014). The
heterogeneity of interventions, measurement tools and
Random Sequence
Generation (Selection
Bias)
Allocation concealment
(Selection Bias)
Blinding of participants
and personal
(performance bias)
Blinding of outcome
assessment (detection
bias)
Incomplete outcome data
(Attrition bias)
Selective reporting
(reporting bias)
Group balance at baseline
Intention to treat analysis
conducted
Groups receive same
treatment (a part from
the intervention)
Beune et al.
(2014)
Guirado et al.
(2011)
Hacihasanoglu &
Goözuöm (2011)
Ho et al. (2014)
Jiang et al. (2007)
Kripalani et al.
(2012)
+++++++
+++++
++++++++
+++++
–– –
––
?
?
–
+?+++? +++
+
–
+
–? – –+?+++
Leiva et al.
(2014)
Ma et al. (2014)
Nieuwkerk et al.
(2012)
Ogedegbe et al.
(2008)
Rinfret et al.
(2013)
Schroeder et al.
(2005)
Smith et al.
(2008)
Wald et al.
(2014)
++++++
+
++++ +
+++++
++++++++
++++++ +
+++++
++++++
++++
––––
–
––
–– –
?
???
?
?
??
???
??
+
–
Figure 2 Methodological quality summary: review authors’ judgements of each methodological quality of each included study.
3006 ©2016 John Wiley & Sons Ltd
A.H. Al-Ganmi et al.
methods precluded meta-analysis of baseline and postinter-
vention rates of adherence for the reviewed studies.
Multifaceted interventions
The effectiveness of multifaceted interventions for enhanc-
ing medication adherence was described and evaluated by
two studies. Ho et al. (2014) used a four stage multi-
faceted intervention that entailed: medication reconciliation
and tailoring, education about medications, collaborative
care and two types of scheduled voice messaging (educa-
tional and medication refill reminder calls). Similarly, Leiva
et al. (2014) evaluated a multifaceted intervention
incorporating motivational interviewing, pillbox reminders,
family support, blood pressure measurements and antihy-
pertensive reminder forms and simplification of dosing reg-
imens in patients with hypertension. Ho et al. (2014)
found that adherence rate improved at 12 months follow-
up by 893% in the intervention arm compared with
739% with usual care for four classes of medications. On
the other hand, Leiva et al. (2014) found no significant
between groups differences in antihypertensive adherence
at 12 months (514% vs. 508%) in intervention and con-
trol groups respectively (Table S2). The Ho et al. (2014)
study was high quality; however, Leiva et al. (2014) did
not employ a blinding process and delivery of the
Table 2 General characteristics of included studies.
Country of
origin United States
United
Kingdom Netherlands China Canada Spain Turkey
4 studies 2 studies 2 studies 2 studies 1 study 2 study 1 study
Ho et al.
(2014),
Kripalani
et al. (2012),
Ogedegbe
et al. (2008),
Smith et al.
(2008)
Schroeder
et al. (2005),
Wald et al.
(2014)
Beune et al.
(2014),
Nieuwkerk
et al. (2012)
Jiang et al.
(2007), Ma
et al. (2014)
Rinfret
et al. (2013)
Guirado et al. (2011),
Leiva et al. (2014)
Hacihasano
glu
and Go€
ozu€
om
(2011)
Participant
diagnostic
group Hypertension
Coronary
Heart
Disease
Myocardial
infarction
Acute Coronary
Syndrome
Undefined; on
lipid-lowering
drugs
8 studies 2 studies 1 study 2 studies 1 study
Beune et al. (2014),
Guirado et al. (2011),
Hacihasano
glu and
Go€
ozu€
om (2011),
Leiva et al. (2014),
Ma et al. (2014),
Ogedegbe et al. (2008),
Schroeder et al. (2005),
Wald et al. (2014)
Jiang et al.
(2007),
Kripalani
et al. (2012)
Smith et al.
(2008)
Ho et al. (2014),
Rinfret et al.
(2013)
Nieuwkerk
et al. (2012)
Practice
setting Primary care
Outpatient
clinics
Community
health centres
Department of
Veterans Affairs
Medical Centre
8 studies 3 studies 2 studies 1 study
Beune et al. (2014), Guirado
et al. (2011), Hacihasano
glu
&Go
€
ozu€
om 2011), Jiang
et al. (2007), Kripalani et al.
(2012), Leiva et al. (2014),
Ogedegbe et al. (2008),
Wald et al. (2014)
Nieuwkerk
et al. (2012),
Schroeder
et al. (2005),
Smith et al.
(2008)
Ma et al. (2014),
Rinfret et al.
(2013)
Ho et al. (2014)
©2016 John Wiley & Sons Ltd 3007
JAN: REVIEW PAPER Medication adherence interventions for patients with cardiac disease
intervention by nurses varied according to their character-
istics and the methods of delivery, possibly resulting in
overestimation of the intervention effect (Tables S2). Over-
all, this type of intervention approach appeared likely to
increase adherence to medications after hospital discharge
post ACS and was costed at $360 per patient per year (Ho
et al. 2014).
Text and mail message interventions
Three studies assessed the effectiveness of text message
(TM) (Wald et al. 2014) and mail message reminders
(Smith et al. 2008, Kripalani et al. 2012). In the Wald
et al. (2014) study, participants in the intervention group
received automatically generated daily TM reminders which
questioned patients whether they had taken their blood
pressure and/or lipid-lowering medications; whether the
message had reminded them to take it; if they had forgot-
ten or whether they had simply not taken it. This study
showed 16% improvement in medication adherence (95%
CI 7–24%, P<0001) at 6 months follow-up and a statis-
tically significant difference between groups of patients
who had stopped medication completely and those who
continued to take <80% of the prescribed regimen
(Table S2). However, participants’ high adherence rates at
baseline and unclear randomization and blinding proce-
dures may have resulted in under or overestimation of
intervention effects (Tables S1).
Two studies applied a less individual approach, one
mailed graphical postcards focusing on refill and other
important reminders to patients with CHD (Kripalani et al.
2012), another focused on improving cognitive aspects of
medication adherence by sending two letters to patients and
to primary care providers describing the importance of
beta-blockade (Smith et al. 2008).Kripalani et al. (2012)
showed a non-significant difference in improvements in
adherence between groups (329% vs. 329% respectively),
whereas the Smith et al. (2008) study improved adherence
rates among patients in the intervention group by 17%,
increasing the days covered to 80% in this group (relative
risk =117; 95% CI =102-129; P=004). The quality of
Smith et al. (2008) study was good in terms of randomiza-
tion methods, intervention and strategies used for applying
the intervention and follow-up. By contrast, graphical
mailed refill reminders failed to improve medication adher-
ence, attributed to quality issues with randomization and
blinding processes (Table S1). Overall, the TM and mail
message approaches appeared potentially effective and fea-
sible strategies as reinforcement for taking medication and
improving medication adherence.
Telephone call interventions
Two studies (Hacihasano
glu & Go€
ozu€
om 2011, Rinfret
et al. 2013) examined the use of structured phone calls
with interactive components to improve medication adher-
ence. Hacihasano
glu and Go€
ozu€
om (2011) randomly allo-
cated patients with hypertension to three groups to receive
a 6-month nurse-based medication educational intervention
alone, educational intervention plus home monitoring for
medication adherence, or a control group. Both intervention
groups received monthly follow-up phone call interviews
providing them with information about hypertension. Simi-
larly, in the Rinfret et al. (2013) study, patients with dual
antiplatelet therapy (DAT) (n =150) were randomized to
either nurse phone calls in 1 week and then at 1 month,
6 months and 9 months to assess adherence, reinforce
optional drug compliance and discuss the factors affecting
adherence or to a control group (Table S2). Both studies
showed a statistically significant increase in medication
adherence using different measures. At 10 months follow-
up, there was a statistically significant increase in regular
medication intake ratios after education in groups A and B
(80%, 85%, respectively, P=0001) but not in the control
group (42%, P>005) (Hacihasano
glu & Go€
ozu€
om 2011).
Combined education (group B) was shown to have a more
positive effect on adherence self-efficacy than education
alone (group A) and no intervention (control group) (7227
(SD 527); 7110 (SD 642); 5685 (SD 610) respectively,
F=83131; P =0001) (Hacihasano
glu & Go€
ozu€
om 2011).
The Rinfret et al. (2013) study showed that participants in
both groups had high adherence to antiplatelet drugs at
12 months, with 992% (ranging from 975-100%) of the
intervention group taking aspirin compared with 902%
(ranging from 842-954%) of the control group; clopido-
grel, 993% (ranging from 975-100%) in the intervention
group vs. 915% (851-960%) % in the control group,
(p <00001). However, the study results may have been
biased by the lack of blinding of patients and intervention
providers, although it was impractical in this study
(Table S1).
Motivational interviewing strategies
Motivational interviewing has been used as an approach to
increase adherence to medication in cardiac patients. Oge-
degbe et al. (2008) conducted a randomized controlled trial
in two community-based primary care practices in the US,
evaluating the efficacy and effects of practice-based motiva-
tional interview (MINT) counselling on medication adher-
ence and blood pressure in 190 African American patients
3008 ©2016 John Wiley & Sons Ltd
A.H. Al-Ganmi et al.
with hypertension. Based on intention-to-treat analysis
using mixed-effects regression, the MINT group achieved a
higher MEMS adherence rate at 12 months follow-up com-
pared with the control group (57% vs. 43% respectively,
P<005), with an absolute between-group difference of
14% (95% CI, 02to27%). The MINT group received
behavioural counselling about medication adherence for 30-
40 minutes at 3, 6, 9 and 12 months, which led to steady
maintenance of medication adherence over 12 months,
while adherence rates declined overtime in the control
group. Similarly, Ma et al. (2014) applied MINT coun-
selling, based on social cognitive theory, to 120 patients
with hypertension from two community health centres in
China. This intervention entailed strategies to promote
adherence to behaviour changes, summarizing the pros and
cons of proposed behaviour changes, setting realistic and
specific goals for behaviour modification and prompting
patients to follow plans for behaviour change (Table S2).
Adherence to medication was improved in the MINT coun-
selling group compared with the control group at 6 months
follow-up (2972 (SD 346) vs. 2530 (SD 311)) respectively,
(t=0039, P=0034). Mean scores for medication adher-
ence were increased within-groups with mean difference
between baseline and 6 months for intervention group of
(2325 (SD 302); 2972 (SD 346)) respectively, (t=0. 039,
P=0034) and (2213 (SD 289); 2530 (SD 311)) (t=0.
039, P=0061) (Table S2). This form of MINT was the-
ory-based and shown to be effective using accepted valid
measures for adherence assessment over longer duration of
follow-up.
Nurse-led counselling and education
Five studies intended to improve medication adherence
using behavioural interventions and education through
nurse-led counselling. Four studies demonstrated no or lit-
tle evidence of effect (Schroeder et al. 2005, Jiang et al.
2007, Guirado et al. 2011, Beune et al. 2014). These
results may be attributed in part at least to feature of the
research methods, such as self-selected populations with
high adherence levels at baseline (Schroeder et al. 2005)
and randomization and blinding processes bias (Jiang
et al. 2007, Guirado et al. 2011, Beune et al. 2014)
(Table S1). Nieuwkerk et al. (2012) revealed that adher-
ence to lipid-lowering medication increased from 95% to
100% in the intervention group and from 90% to 95%
in the control group. At 18 months follow-up, the inter-
vention group had higher adherence to statin therapy than
the control group (939 (SD 015) vs. 886 (SD 015))
respectively, with an absolute difference between groups
of 053 (002-105), (r=036, P<001) (Table S2).
With 201 patients on statin therapy randomized to receive
nurse-led multifactorial cardiovascular risk-factor coun-
selling or standard care, statistically significant outcomes
were attributed to the more extensive personal contact
with the nurse practitioner and risk-factor counselling in
the intervention group compared with the control group.
Overall, most studies demonstrated no improvement in
outcomes from nurse-led behavioural interventions
(Schroeder et al. 2005, Jiang et al. 2007, Guirado et al.
2011, Beune et al. 2014), while Nieuwkerk et al. (2012)
study appeared to offer an opportunity to improve medi-
cation adherence. However, taking into consideration the
baseline difference between groups, these study findings
should be interpreted with caution.
Discussion
This review of interventions to enhance adherence to medi-
cations in cardiovascular care highlighted not only the vary-
ing effectiveness of approaches trialled but also the varying
methods of evaluation. The evidence of effectiveness pre-
sented for these interventions was inconsistent, due at least
in part to the different cardiac disease populations and
adherence measurement methods used in these studies.
Results were not materially affected by age, sex or smoking
(Wald et al. 2014), but the impact of socio-economic status
could not be determined; however, examination of the
effect of these factors went beyond the review research
question (Jiang et al. 2007).
Motivational interviewing, either alone or combined with
another adherence approach such as phone or text message
education and reminders, appeared the most promising
behavioural intervention for improving medication adher-
ence, with potential for wide application across patients
with different forms of cardiac disease. Interventions that
used motivational interviewing (MINT) strategies were suc-
cessful at maintaining medication adherence over time
among hypertensive patients (Ogedegbe et al. 2008). The
results support those of previous studies, demonstrating that
MINT may be a useful approach for addressing medication
adherence (DiIorio et al. 2008), because it enhance patient
readiness to change, increase their confidence in their ability
to overcome barriers and increase self-motivation to achieve
desired outcomes (Rollnick & Miller 1995). This approach
entailed setting realistic and specific goals for behaviour
modification and prompted patients to follow their plan for
behaviour change. This can be achieved when trained
nurses integrate adherence behaviour into patients’ daily
routines and reinforce the positive effect of MINT by
©2016 John Wiley & Sons Ltd 3009
JAN: REVIEW PAPER Medication adherence interventions for patients with cardiac disease
follow-up using phone calls, text messaging or mails as a
mean of multifactorial intervention.
Multifaceted interventions also demonstrated statistically
significant improvement in medication adherence (Ho et al.
2014). Study findings were consistent with other successful
multifaceted interventional studies, which have included
medication review with a specific focus on regimen simplifi-
cation (Bernsten et al. 2001), individualized patient educa-
tion combined with medication reminders (Hawe &
Higgins 1990), or a dose administration aid (Lee et al.
2006). These results also accorded with a study (Edworthy
et al. 2007) that found statistically significant improvement
in adherence for both beta-blocking and lipid-lowering
agents with counselling by nurses and pharmacists along
with video, printed material and phone follow-up. Multi-
faceted interventions have broadly demonstrated promising
results, but make it difficult to draw conclusions in favour
of any particular combination of interventions or intensity
because of the heterogeneity and complexity of interven-
tions, compounded by multiple adherence measures
(Topinkov
aet al. 2012) and drug classes (van Eijken et al.
2003). The cost of these interventions is also an important
consideration for roll-out, this could not be determined as
interventions were not described in sufficient detail.
A common element of many medication adherence inter-
ventions was education. However, the methods of deliver-
ing education differed and outcomes were inconsistent.
Effective nurse-based medication educational interventions
included 6-monthly face-to-face education sessions (Haci-
hasano
glu & Go€
ozu€
om 2011) about the important of regu-
lar medication taking, medication efficacy, possible side
effects and the importance of follow-up visits. Medication
education was also successfully combined with automatic
voice message reminders at 1 week and 1 month after hos-
pital discharge for 12 months (Ho et al. 2014). By contrast,
written medication educational materials delivered by a
nurse combined with three structured counselling sessions
was not associated with statistically significant improve-
ment in medication adherence (Guirado et al. 2011, Beune
et al. 2014).
Comparisons across assessments of adherence were also
difficult. The medication event monitoring system (MEMS),
one of the most reliable objective assessment methods was
expensive and not readily available for some dose forms
(Remington et al. 2007, van den Boogaard et al. 2011).
Subjective self-reporting measures are commonly used as
they are relatively simple and less expensive; a number are
well-validated and have been strongly correlated with
objective measures of adherence in different populations
(Nguyen et al. 2014).
For text and mail message interventions, studies showed
similar improvements in medication adherence, at 16%
(Wald et al. 2014) and 17% (Smith et al. 2008), respec-
tively. These findings are consistent with recent RCTs
reporting that bidirectional text messages resulted in statis-
tically significant improvement in anti-retroviral treatment
adherence among patients with Human Immunodeficiency
Virus (Lester et al. 2010) and with hypertension (M
arquez
Contreras et al. 2005). Similarly, phone call interventions
significantly improved adherence self-efficacy to antihyper-
tensive medications at 10 months follow-up when com-
bined with health promotion theory-based medication
education and behavioural modification targeting patients’
lifestyles (Hacihasano
glu & Go€
ozu€
om 2011). Cutrona
et al. (2010)’s review concluded that phone calls both by
trained lay people and by a nurse yielded statistically sig-
nificant improvements in cardiovascular adherence. Like-
wise, tailored telephone call nursing interventions reduced
the time commitment, the cost for the care provider, pro-
vider costs and improved medication adherence for
patients with chronic diseases (Bosworth et al. 2009).
However, a review by Mansoor et al. (2013) found that
informational interventions had little or no impact on
improving medication adherence. This could be due to
how well healthcare providers delivered the interventions,
the patient groups, study design and differences in the rel-
ative contribution of each element to the intervention. For
example, information supplied passively to the patient
may not be adequate and the additional element of requir-
ing a response from the patient may be what was respon-
sible for statistically significant change. All in all, using
technology in the form of phone message intervention pro-
vided by nurses appeared feasible, cost-effective and likely
to be an effective tool to improve medication adherence in
resource-limited settings.
The results of nurse-led interventions were mixed
although one study (Nieuwkerk et al. 2012) was success-
ful in increasing adherence rates for lipid-lowering medi-
cations by enhancing patients’ knowledge through
structured counselling sessions. A similar intervention was
shown to be beneficial in patients with hypertension
(Logan et al. 1983). Nurse-led interventions have also
failed to show positive effects on medication adherence in
other populations. For example, Clarke et al. (2002)
found no significant between-group differences in mean
change scores of medicine taking after 12 months of a
nurse-led diabetes management programme. However,
overall, the evidence is not adequate, with current studies
limited by short follow-up, small sample size and incon-
sistent adherence measures.
3010 ©2016 John Wiley & Sons Ltd
A.H. Al-Ganmi et al.
To date, of nurse-delivered interventions to improve
adherence to cardiovascular medications, multifaceted inter-
ventions appear to offer the best opportunities to optimize
medication adherence, with component behavioural inter-
ventions in the form of motivational interviewing, educa-
tional content, text and/or phone messaging showing the
greatest success.
This review has some limitations. All papers reviewed
were from English-language sources and published since
2004; study results may not represent less contemporary
non-English publications. The wide variety of medication
adherence measurement methods used in these studies made
it difficult to detect changes in adherence to medications,
although, most studies did use validated self-report ques-
tionnaires. Finally, the lack of concealment of randomiza-
tion allocation, blinding, self-reporting bias and high rate
of participant dropout in some studies could compromise
the integrity of the study data. Hence, for each study, we
examined potential biases that might explain differences
among studies.
Conclusion
The prevalence of CVD is rising rapidly worldwide along-
side emerging new and complex medication regimens
which challenge both patients and healthcare providers
(Hauptman 2008). Of the interventions intended to
improve adherence to cardiovascular medications tested by
studies in this review, multi-component interventions, tai-
lored to address the patients’ health behaviours, appeared
to offer most promise. Combined interventions need to be
detailed and employ multiple approaches such as motiva-
tional interviewing and education that target the desired
behaviour change and reinforcement of these behaviours
such as with phone or text message strategies. However,
while this review provides pointers for promising interven-
tion approaches available to nurses, further studies are
required to develop and test ways to accommodate these
promising interventions in daily practice. It is imperative
that interventions chosen are theory-based and evaluated
in robust trials to demonstrate effects on clinical out-
comes, feasibility in usual practice settings and sustainabil-
ity. There is clearly a future role for technology in
automating management of, for example, text and mail
messaging. Healthcare providers in primary and secondary
health settings should maximize the health benefits offered
by medications by adopting those strategies shown to be
effective at enhancing patients’ adherence to their medica-
tions. Researchers should clearly justify and specify
methodologies to generate a cumulative body of
knowledge that can be used to inform clinical practice.
Further investigation of factors affecting long-term medica-
tion adherence is warranted to enable better targeting of
interventions.
In summary, this review flags the enormous potential for
future research and nursing practice development to signifi-
cantly contribute to the care and outcomes of cardiac
patients through optimizing the benefits offered by medica-
tion schedules. Review findings indicate promising out-
comes, but also highlight the current lack of high quality
research and knowledge deficits in this field.
Funding
This research received no specific grant from any funding
agency in the public, commercial or not-for-profit sectors.
Conflict of interest
No conflict of interest has been declared by the author(s).
Author contributions
All authors were involved in initial conception of the paper
and in the design of the systematic review protocol. All
authors contributed to the preparation of the final manu-
script. AA, LP and LG take responsibility for all aspects of
the reliability and freedom from bias of the data presented
and their discussed interpretation.
All authors have agreed on the final version and meet at
least one of the following criteria [recommended by the
ICMJE (http://www.icmje.org/recommendations/)]:
•substantial contributions to conception and design,
acquisition of data or analysis and interpretation of
data;
•drafting the article or revising it critically for important
intellectual content.
Supporting Information
Additional Supporting Information may be found in the
online version of this article at the publisher’s web-site.
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