DOI: 10.1111/1755-5922.

12211

UNSOLICITED REVIEW

Adherence to therapies for secondary prevention of

cardiovascular disease: a focus on aspirin

Kathleen A. Packard1 | Daniel E. Hilleman1,2

1
Department of Pharmacy
Practice, Creighton University School of
Pharmacy and Health Professions, Omaha,
NE, USA
2
The Cardiac Center of Creighton University
School of Medicine, Omaha, NE, USA
Correspondence
K.A. Packard, Department of Pharmacy
Practice, Creighton University School of
Pharmacy and Health Professions, Omaha,
NE, USA.
Email: kpackard@creighton.edu
Summary
Aim: Suboptimal adherence to medications taken chronically for secondary preven-
tion of cardiovascular disease (CVD, e.g., aspirin) continues to burden the healthcare
system despite the well-­established benefits of prevention. We conducted a literature
search to examine patient adherence to medications for secondary prevention of
CVD—as evaluated by prescription refill data, electronic medication monitors, pill
counts, and physiologic markers—to better identify an unmet need for measures to
improve patient adherence to these therapies.
Methods: English-­language articles were obtained from the PubMed database using
the following key words or combinations thereof “adherence,” “compliance,” “second-
ary prevention,” and “cardiovascular disease.” Publications that provided adherence
data only for primary prevention, lacked data on medication adherence (e.g., focus on
guideline adherence), emphasized quality-­of-­care outcomes, or focused on outcomes
of acute interventions were excluded.
Results: Multiple patient-­, disease-­, and treatment-­related factors may contribute to
poor adherence to treatment regimens, and therefore, a multifactorial approach will
likely be needed to improve compliance with prescribed treatments for CVD. Although
no magic bullet exists to assure full adherence, adherence programs coupled with
patient counseling and education (inclusive of over-­the-­counter therapies), along with
treatments that are less complex or avoid bothersome adverse effects, are more likely
to be associated with successful outcomes.
Conclusion: Given the burden of CVD to the community and the healthcare system,
nonadherence to CVD-­preventative medications such as aspirin remains a substantial
area of unmet need and represents a key opportunity for the development of quality-­
of-­care enhancement programs to improve health outcomes in this patient population.

KEYWORDS
adherence, aspirin, cardiovascular disease, diabetes mellitus, morbidity and mortality,
over-the-counter

1 |  INTRODUCTION
Atherothrombotic disease is the leading cause of mortality among
individuals in the United States, with heart disease and stroke con-
tributing to approximately 23.7% and 5.1% of deaths, respectively, in
2011.1 Approximately 7.6 million and 6.6 million adults have experi-
enced myocardial infarction (MI) or stroke, respectively.2 Peripheral
arterial disease (PAD), a strong predictor of cardiac and cerebrovas-
cular mortality,3 is another life-­threatening condition that affects 8.5
million (~7.2%) US adults over the age of 40 years.4

Cardiovascular Therapeutics 2016; 34: 415–422 wileyonlinelibrary.com/journal/cdr © 2016 John Wiley & Sons Ltd  |  415
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416       Packard and Hilleman
Hospitalizations for atherothrombotic disease occur with high
frequency. In 2009, 1.35 million individuals were hospitalized for cor-
onary heart disease (CHD).5 Approximately 691 000 hospitalizations
per year have been attributed to acute ischemic stroke.6 Another ~1
million individuals were discharged from the hospital for heart failure
7
in a single year. Fortunately, rates of CHD and cerebrovascular dis-
ease have shown a trend toward decline during the last several years.1
Age-­adjusted mortality from CHD also decreased, by 66% in men and
67% in women, from 1980 to 2009.5 Likewise, age-­adjusted mortality
from stroke has declined, from 48.0 to 37.9 persons per 100 000, from
2005 to 2011.1
Overall reductions in mortality rates have been attributed, at least
in part, to the availability of effective pharmacologic therapies, includ-
8
ing antiplatelet therapies (e.g., aspirin), antihypertensive therapies
(e.g., ß-­blockers and angiotensin-­converting enzyme [ACE] inhibitors
or angiotensin receptor blockers [ARBs]),9,10 and dyslipidemia treat-
11
ments (e.g., statins). However, despite the substantial progress
that has been made in reducing the rate of cardiovascular disease
(CVD)-­related mortality, nonadherence to medications for CVD pre-
vention, including aspirin, continues to negatively impact patient out-
comes,12–15 adding to the already high burden of these diseases on
16
the healthcare system.
The term adherence is often considered in a variety of contexts
(e.g., lifestyle modifications, evidence-­based guidelines, medication);
however, a sizable body of published evidence has focused on med-
ication adherence. This narrative review summarizes the data from
primary research and review papers that examined patient adher-
ence to medications for secondary prevention of CVD events (with
a focus on aspirin), as measured by prescription refill data, elec-
tronic medication monitors, pill counts, and physiologic markers.
Implications of medication nonadherence in the chronic treatment
of CVD are substantial; therefore, understanding the barriers to
adherence and the implications of suboptimal adherence is vital to
improving treatment compliance and health outcomes in this large
patient population.
2 |  METHODS
The PubMed database was searched for English-­language articles with
no time limitation up to June 21, 2015, using the following key words:
“adherence,” “compliance,” “secondary prevention,” and “cardiovas-
cular disease.” Additional database searches were performed using
the following search strings: (“adherence” OR “compliance”) AND
“secondary prevention” AND “cardiovascular disease.” Outcomes
of the primary literature search yielded a total of 201 publications,
from which approximately 25% (52) were ultimately selected for fur-
ther consideration (41 original articles and 11 reviews). Articles that
contained adherence data only in the setting of primary prevention,
lacked data on medication adherence (e.g., focus on guideline adher-
ence), emphasized quality-­of-­care outcomes, or focused on outcomes
of acute interventions were excluded. Application of these delimit-
ers led to the exclusion of approximately 90% of the 52 citations.
Consultation of more recent review articles and treatment guide-
lines for general information on medication adherence for secondary
prevention of CVD was also performed. Lastly, bibliographies from
included articles and guidelines were manually reviewed for additional
relevant studies. A majority of the literature cited the current manu-
script was identified from manually reviewing previous publications
on topic of adherence in the secondary prevention of CVD.
2.1 | Prevalence of medication nonadherence
Patients are considered adherent to treatment when they actively,
voluntarily, and collaboratively participate in the choice and goals
of therapy, as well as planning and implementation of the treatment
regimen.17 In the literature, medication adherence rates of 80% are
generally considered adequate for patients with established CVD or
at risk for CVD.18 Thus, in this context, medication adherence rates
<80% should be considered suboptimal to varying degrees, depend-
ing on the level of importance of a drug class to clinical response by
disease state (e.g., adherence to glucose-­lowering medications in
patients with diabetes).
Poor adherence to medications for secondary prevention of car-
diovascular (CV) events and mortality may be especially deleterious.
A number of studies and meta-­analyses have reported adherence
rates of ~60% to 75% for chronic treatments for secondary preven-
tion in CVD, with aspirin having one of the lowest reported rates of
adherence (65%) among these therapies (Figure 1).19–23 In one meta-­
analysis, adherence (based on pharmacy prescription refill data) to
medications for secondary prevention during a median 24-­month
period was 66%.19 Although some between-­drug class variability was
evident, there was generally no statistical difference, suggesting that
adherence was not linked to any specific drug class.
Another study, of 1114 patients with various clinical manifes-
tations of vascular disease (e.g., critical limb ischemia, claudication,
acute limb ischemia), reported adherence rates of 64% to 91% for
aspirin, 43% to 83% for statins, and 49% to 66% for ACE inhib-
itors.21 Lastly, long-­term (10-­year) adherence rates for patients
with CVD taking aspirin, statins, or combination aspirin plus sta-
tin therapy for secondary prevention were 60%, 64.5%, and 76.0%,
respectively.23
A retrospective study of prospective data from the Prospective
Registry Evaluating Myocardial Infarction: Events and Recovery
(PREMIER) and Translating Research Investigating Underlying
Disparities in AMI Patients Health Status (TRIUMPH) registries
(n=6838), both of which included patients with acute MI, showed that
only up to 61.5% of patients reported “persistence” (i.e., self-­reported
medication use) with their prescribed secondary prevention regi-
men after 12 months.24 The persistence rate was even lower among
patients at intermediate (59.3%) or high risk (45.9%) of a CV event.24
Aspirin was the only secondary prevention medication that was asso-
ciated with a significantly increased risk of lack of persistence in both
intermediate-­risk (relative risk [RR], 0.96; 95% confidence interval [CI],
0.95–0.99) and high-­risk (RR, 0.92; 95% CI, 0.89–0.95) patients when
compared with their low-­risk counterparts.24
Packard and Hilleman
F I G U R E   1   Summary of patient adherence in secondary
prevention of CVD. Adherence is suboptimal for all medication
classes in secondary prevention settings. Adapted with permission
from Naderi SH, et al.19 ACE; angiotensin-­converting enzyme, ARB;
angiotensin receptor blocker, CCB; calcium channel blocker, CI;
confidence interval
2.2 | Health outcomes of nonadherence in secondary
prevention of CVD
Nonadherence is associated with higher morbidity and mortality,
resulting in ~130 000 (41% of 320 000) avoidable deaths each year
in the United States. 19
A systematic review of adherence in patients
with established CVD found that for every 10% increase in medical
adherence, an additional 6.7% of CV events could be prevented over
10 years.22 In terms of reducing blood cholesterol levels to prevent
atherosclerotic CVD, it has been suggested that patient adherence to
medications is the single greatest opportunity to improve lowering of
low-­density lipoprotein cholesterol (LDL-­C).25
In high-­risk patients hospitalized with acute MI and subsequent-
ly discharged on aspirin, ß-­blockers, statin therapy, or a combina-
tion of all three medications, mortality was highest among patients
who discontinued use of all medications (hazard ratio, 3.8; 95% CI,
26
1.9–7.7; Figure 2). However, discontinuation of any of these treat-
ments increased the risk of mortality, with nearly 2-­fold and 3-­fold
increases seen with discontinuation of aspirin and statin therapies,
respectively.26
The large observational study, the REduction of Atherothrombosis
for Continued Health (REACH) registry, followed 37 154 patients with
atherothrombotic disease of coronary, cerebrovascular, and/or PAD
origin for 1 year to assess medication adherence, which was deter-
mined based on patient self-­report. The primary outcome was a com-
14
posite endpoint of CV mortality, MI, or stroke at 4 years. Only 46.7%
of patients at baseline and 48.2% at 1 year were fully adherent with
guideline-­recommended medications for secondary prevention, such
as antiplatelet agents, lipid-­lowering therapies, and antihypertensive
agents. At the time of enrollment, aspirin was the most commonly
administered antiplatelet agent, used by 84% of patients. Patients who
were fully adherent at baseline and 1 year had the lowest incidence
|
      417
F I G U R E   2   Mortality risk by medication adherence subgroup.
Adjusted hazard ratios for patient subgroups. Error bars represent
95% confidence intervals. Discontinuation of any treatment for
myocardial infarction was associated with an increased 12-­month
mortality rate. Reprinted with permission from Ho PM, et al. 26
of all-­cause mortality vs those who were nonadherent at both time
points (P<.0001). Conversely, nonadherence to medications at base-
line or 1 year increased the risk of all-­cause and CV mortality at 4 years
by approximately 30% (P<.001).14 Those who were consistently non-
adherent (i.e., nonadherent at baseline and at 1 year) and negative
converters (those who were compliant at baseline but nonadherent at
1 year) fared worst (Figure 3).14 Cumulative incidence of CVD, MI, or
stroke showed a similar trend.14
2.2.1 | Aspirin
Aspirin is regarded as first-­line antiplatelet therapy for secondary pre-
vention and as primary prevention of CV events in select patients27;
therefore, patient adherence to aspirin therapy has been evaluated in
many studies. In a meta-­analysis of six trials that evaluated withdrawal
of aspirin therapy among patients with known CHD, nonadherence
or discontinuation of aspirin imparted a 3-­fold increased risk of over-
all (odds ratio, 3.1; 95% CI, 1.8–5.6; P=.0001) thrombotic events and
a 2-­fold increase in the risk of coronary artery disease (odds ratio,
1.8; 95% CI, 1.5–2.2) and coronary artery bypass grafting (odds ratio,
2.4; 95% CI, 1.6–3.1).15 In patients who experienced a CV event,
the mean time from aspirin withdrawal to occurrence of the event
was 10.7 days, which mirrors complete turnover of platelet popula-
tion (i.e., the platelet life cycle).15 Among the 3 studies that enrolled
patients who had acute coronary syndrome or were taking secondary
prevention therapies for CVD, risk of adverse thrombotic events was
increased nearly 2-­fold (1.8; 95% CI, 1.5–2.2; P<.00001) in patients
who discontinued or were not adherent to the aspirin regimen.15
2.2.2 | High-­risk populations: diabetes mellitus
In contrast to the declining rates of CHD and cerebrovascular disease
mentioned earlier, prevalence of diabetes is on the rise. If current
 |
418       Packard and Hilleman
five
epidemiologic trends hold true, one in three US adults will likely
develop diabetes in their lifetime.28 Patients with type 1 or 2 diabetes
have high long-­term risk for a CV event,29 and risk of CV mortality
is approximately 1.7-­fold higher in this group, compared with those
without diabetes.30 In addition, the complexity of therapies30 for
management of diabetes and its comorbidities presents challenges to
patient adherence.
The benefits of medication adherence on mortality in patients with
diabetes were shown in a retrospective study of 11 532 patients with
diabetes receiving oral hypoglycemics, antihypertensives, and statin
13
therapy for both secondary and primary prevention. Adherence was
measured by the percentage of days covered for a filled prescription,
and the primary outcomes were all-­cause hospitalization and all-­cause
mortality.13 A significant increase in risk of both outcomes was seen
among nonadherent patients (P<.001 for both comparisons), but med-
ication adherence was associated with incremental improvement in
outcomes.13 For each 25% improvement in medication adherence,
there was a significant reduction in risk of all-­cause hospitalization
(OR, 0.83; 95% CI, 0.79–0.88; P<.01) and all-­cause mortality (OR,
0.75; 95% CI, 0.68–0.83; P<.01).13 Significant improvements in mul-
tiple cardiovascular parameters were also observed with increased
medication adherence13; however, the extent to which improvement
in each of these parameters may have contributed to reductions in all-­
cause hospitalization and mortality is unknown.
2.3 | Nonadherence to chronic therapies is a
complex, multifactorial challenge
Multiple factors affect a patient’s adherence to long-­term use of CVD
preventive medication. Reasons for poor adherence or nonadher-
ence may be related to the treatment itself: its ease of use or lack
thereof, frequency of dosing, or adverse effects. Patient-­specific fac-
tors, such as age, mental health, or other existing medical conditions
(e.g., diabetes), and socioeconomic factors (i.e., education level, health
F I G U R E   3   Kaplan–Meier summary
of all-­cause mortality in patients grouped
according to adherence to antiplatelet
therapy, lipid-­lowering therapy, and
antihypertensive therapy at baseline
and at 1 y. Consistent nonadherers
were nonadherent at baseline and at
1 y, whereas consistent adherers were
adherent at baseline and at 1 y. Adapted
with permission from Kumbhani DJ, et al.14
CA; consistent adherers, CNA; consistent
nonadherers, NC; negative converters, PC;
positive converters
literacy, access to social support) can also influence patient compli-
ance (Figure 4).18,20,22,31–35 Lastly, healthcare system-­related factors,
such as lack of continuity of care, inadequate patient education, or
poor doctor–patient relationships, can negatively impact adherence
to medication.18,20,22,31–35
2.3.1 | Treatment-­related factors
affecting adherence
In patients taking chronic therapy for CVD, frequency of dosing was
inversely related to adherence: the higher the dosing frequency, the
lower the patient adherence.36–38 In a study of 91 patients with dia-
betes using oral antidiabetic agents, adherence to oral treatments
taken 3 times daily was 38%, compared with 79% for once-­daily
therapy.36 Patients with pulmonary embolism and deep vein throm-
bosis were 62% more likely to be adherent to their once-­daily treat-
ment than those who received twice-­daily dosing (P<.001 for both
comparisons).37
In a study of 1.08 million adults with a prescription for a once-­daily
or twice-­daily antidiabetic, antihyperlipidemic, antiplatelet, or ­cardiac
agent, 1-­year adherence (measured as the medication possession
ratio [MPR]) was higher for once-­daily vs twice-­daily dosing, with the
greatest difference observed for antiplatelet agents (Table 1).38 In this
case, twice-­daily treatments, primarily aspirin/dipyridamole, cilostazol,
and ticlopidine, were associated with a 42% worsening in adherence
(P<.01 vs once-­daily treatment). This equated to an approximately 30%
improvement in patient compliance with use of once-­daily therapy.38
A 2010 observational study examined 340 patients at risk for
or with confirmed CVD who were receiving low-­dose aspirin (75–
325 mg/d).39 Patients were assessed for the impact of upper gastroin-
testinal (GI) symptoms on nonadherence (defined as low-­dose aspirin
intake of <75% during a 3-­month period). Most (75%) patients were
low-­dose aspirin-­naïve at study entry, with no upper GI symptoms
reported during the previous 14 days. Approximately two-­thirds of
Packard and Hilleman
F I G U R E   4   Multifactorial causes of
nonadherence to chronic medications for
CVD.18,20,22,31–35 CVD; cardiovascular
disease, OTC; over-­the-­counter
T A B L E   1   Adherence (measured by the medical possession ratio [MPR]a) by therapeutic class and dosing frequency
Adjusted mean MPR
qd (n=1 384 226)
Overall adherence 0.66
Adherence by therapeutic class
Antidiabetic agents n=72 152 0.69
Antihyperlipidemic agents n=532 480 0.63
Antiplatelet agents n=39 222 0.68
Cardiac agents n=740 372 0.63
bid; twice daily, qd; once daily.
a
Medical possession ratio (MPR) is defined as the number of days of medication was supplied from the first prescription fill date up to 365 days, divided by
365 days. Adapted with permission from Bae JP et al.38
patients (65%) were taking low-­dose aspirin as secondary prevention
or high-­risk primary prevention. Among aspirin-­naïve patients, the
onset of upper GI symptoms was rapid, with 19% reporting symp-
toms on Day 1 of the study, which increased to 46% during Week
1 (cumulative). Overall, 61 (18%) patients were nonadherent to low-­
dose aspirin during the 3-­month period. Importantly, patients with
upper GI symptoms during the day were significantly less likely to
be adherent to aspirin regimens (P<.01). Other therapeutic classes
used in the treatment of CVD are likewise associated with adverse
effects (to a variable extent), including statin-­induced myalgia, ACE
inhibitor-­induced cough, and ß-­blocker-­induced fatigue; these
adverse effects have been known to result in nonadherence or out-
right discontinuation.40–42
2.3.2 | Patient-­related factors affecting adherence
Patient perceptions of the brevity of their illness or of how critical
a medication may be to health or survival are subjective and may
be influenced by a number of factors, including the degree to which
patients understand their disease state and a lack of perceived need
or benefit from recommended medication(s).34,43 The latter may be
especially true for patients taking antiplatelet medications (e.g., aspi-
rin) for in-­stent thrombosis, statin therapy for dyslipidemia, or therapy
for hypertension, because clinical symptoms of disease are not always
outwardly evident for individuals in these populations.34 Patients with
diabetes, for example, may perceive their glucose-­lowering therapy to
be more important to disease management than antihypertensive or
lipid-­lowering therapies.43
|
      419
bid (n=56 028) % qd difference from bid P value
0.57 +15.8% <.01
n=14 568 0.67 +3.0% <.01
n=11 361 0.52 +21.2% <.01
n=8577 0.48 +41.7% <.01
n=21 504 0.63 0% .50
Patient perceptions of drug value or effectiveness often differ for
prescription vs over-­the-­counter (OTC) therapies (e.g., aspirin) or are
often influenced by medication costs.44,45 Patients may consider the
consequences they face when not complying with prescription drug
instructions to be more dangerous than ignoring the instructions for
proper use of OTC drugs.44 Additionally, patients have shown a sub-
stantially greater placebo effect when they believed they were receiv-
ing an expensive treatment compared with those who were told they
were receiving a less expensive treatment for their condition.45
Fear of drug toxicity or occurrence of adverse effects is another
potential cause of medication nonadherence.18,34 Patients should
be sufficiently counseled on expectations for potential treatment-­
related adverse effects or on strategies to proactively manage adverse
effects.46 Age is also a risk factor for nonadherence.33 Although
­elderly patients take more medications and medication combinations
for chronic medical conditions and may experience diminishing cogni-
tive skills that increase the risk of nonadherence,18 older age is typi-
cally associated with increased adherence to treatment.47,48 Current
smoking status and diabetes were risk factors for self-­reported poor
adherence to aspirin, ß-­blockers, and aspirin + ß-­blocker combination
therapy.33 This finding has also been reported in other studies of sec-
ondary prevention for CVD.20 Nonwhite race, depression, and cogni-
tive impairment are also risk factors for nonadherence.18,34
In addition, lower literacy, high medication costs, and lack of
social support have been shown to negatively impact adherence.18
Healthcare literacy remains generally inadequate in the United States,
and lack of disease treatment understanding is associated with poor
adherence.34,49 According to data from a 2003 national household
 |
420       Packard and Hilleman
survey, 36% of US adults possess health literacy skills that are basic or
50
below basic. When this is translated into patient outcomes, patients
with lower health literacy may have less favorable disease outcomes,
use fewer preventive services, and are more likely to be hospitalized
51–53
for their condition(s). For patients with diabetes, suboptimal
health literacy was associated with worse control of blood glucose
levels.54
2.3.3 | Healthcare system-­related factors
affecting adherence
Access to medication represents another potential barrier, with pay-
ers (e.g., formulary considerations) and national and state govern-
ments increasingly influencing which therapies will be reimbursed and
to what extent.55,56 Additionally, out-­of-­pocket medication costs are
a substantial driver of treatment decisions for many patients.55–57
Finally, many patients do not have well-­developed relationships
with their healthcare providers or may not be able to effective-
ly communicate their particular symptoms, needs, or challenges.18
Conversely, patient education efforts may be lacking. In one study,
fewer than 50% of patients discharged from the hospital were able
to list all of their medications or remember what each medication was
for, indicating a greater need for improved discharge counseling.18,58
Adherence decreased in patients receiving more complex medication
regimens.59 Finally, lack of strong familial or social support may also
present a barrier to medication adherence.60,61
2.4 | Cost of nonadherence
In general, the use of therapies to prevent secondary cardiovascular
events lowers overall cost of cardiovascular disease, with the increased
cost of medication potentially being outweighed by the prevention of
expensive hospitalizations.62–64 Increasing patient adherence to these
medications increases cost-­effectiveness,22 with cost savings being
65
largest with greater levels of adherence. Preventative aspirin ther-
apy reduces overall cost compared with no treatment,65 even when
65,66
taking GI bleeding events and baseline diabetes comorbidity into
65
consideration. This may be especially true when dual antiplatelet
therapy (i.e., aspirin + clopidogrel) is administered, as multiple studies
have shown that this treatment strategy is more cost-­effective than
aspirin alone in several cardiovascular patient populations (reviewed
67
in Arnold SV, et al., 2012 ). These cost savings have prompted explo-
ration of interventions aimed at increasing adherence to preventative
cardiovascular therapies and may be cost-­effective in some patient
populations, despite the additional start-­up costs required.68
2.5 | Limitations
This review was limited to articles published in English, with a primary
focus on aspirin and measurement of prescription drug adherence
using tools with inherent disadvantages. In the absence of the abil-
ity to measure and/or routinely monitor serum blood levels because
of practical and economic barriers, studies have relied on adherence
methodologies that suffer from limitations. For instance, prescription
refill count is the most common method of assessing adherence; how-
ever, one cannot assume that the drug was taken before a refill was
requested or that the prescription was filled by only one pharmacy.19
Other indirect measures of adherence, including patient self-­
reports, pill counts, assessment of clinical response, patient diaries,
and electronic medication monitors, all have limitations. Self-­report
measures may be affected by poor patient recall or a desire on the part
of the patient to report overly positive adherence numbers. Likewise,
pill counts fail to convey when the medication was taken, and patients
may manipulate the data by dumping pills.18 For example, with the
exception of a small number of studies performed outside of the
United States, adherence to aspirin therapy has only been measured
through patient reporting. Because platelet function testing is not rou-
tinely performed by healthcare providers, there is no standard physi-
ologic monitoring for aspirin in the way that providers monitor blood
pressure for ß-­blockers and ACE inhibitors and lipid panels for statins.
These inherent limitations and lack of a “gold standard” for assess-
ment of medication adherence point to the difficulties of capturing
data that accurately reflect real-­world adherence.18 Nevertheless,
it should be apparent that much has been gained by applying the
available methods with regard to furthering our understanding of
adherence and patient outcomes, and implications for the healthcare
system.
3 | CONCLUSION
The causes of poor or suboptimal adherence to drug therapies are
multifactorial, involving patient perceptions and preferences, socioec-
onomic considerations, and a range of disease-­ or treatment-­specific
factors. Patient age and mental health and smoking status can impact
treatment adherence,33,34 as can a patient’s perception of the sever-
ity of his or her illness.34,43 It is common for patients to perceive OTC
treatments as being less important or effective compared with pre-
scription drugs.44,45 In addition, frequency of dosing has been noted
to influence adherence, with a higher dosing frequency associated
with lower patient adherence rates.38 As well, concerns about drug
toxicity or occurrence of adverse effects may impact patients’ compli-
ance with their therapeutic regimens.18,34 Inadequate healthcare cov-
erage, low income status, or high out-­of-­pocket costs can also affect
adherence.34 In addition, many high-­risk patient groups, such as those
with diabetes, are less likely to adhere to twice-­daily or thrice-­daily
dosing.
Although the causes of nonadherence are complex and multi-
factorial, adherence programs coupled with treatment regimens that
involve less frequent dosing and fewer adverse effects are likely to
offer the best chance for achieving successful outcomes. Because of
the OTC status of aspirin, an effective and established antiplatelet
therapy for secondary prevention of cardiovascular disease, adherence
is likely further diminished through lack of perceived benefit, as well as
deficiencies in terms of setting expectations during patient counseling.
Assessment of the value of improving adherence to OTC prevention
Packard and Hilleman
therapies through a written prescription or augmented education
efforts is worthy of further consideration. Until such time as human
behavioral issues and treatment barriers are surmounted, the search
for “adherence nirvana” will no doubt continue.
ACKNOWLE DG ME NTS
Technical editorial and medical writing assistance was provided by
Mary Beth Moncrief, PhD, and Larry D. Nelson, PhD, Synchrony
Medical Communications, LLC, West Chester, PA. Funding for
this support was provided by New Haven Pharmaceuticals, Inc,
Bransford, CT.
CO NFLI CT OF I NTE RE ST
KA Packard reports no potential conflicts of interest. DE Hilleman
reports relationships with Bristol–Myers Squibb and Novartis. The
authors did not receive any compensation for development of this
manuscript. New Haven Pharmaceuticals, the study sponsor, did not
actively contribute to the content or have role in the decision to sub-
mit, but reviewed the copy for scientific accuracy.
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