4. Discussion
The present study has highlighted that 70% of the patients on secondary
prevention therapy for CVD have an inadequate adherence in the National
Institute of Cardiology ”Ignacio Chávez” in Mexico City. In agreement
with this finding, a population-based study in Taiwan reported statin
discontinuation of 68% at five years.7 These results
contrast with previously reported in the United States, where adherence
ranged between 50%8 and 87%9within the first year of treatment initiation, declining up to
45%7 in the second. Although our study did not intend
to assess adherence over time, our adherence rate may be one of the
lowest reported, reflecting the discrepancies observed across countries
and ethnic groups.
According to the WHO, nonadherence arises from the interplay between
patient-related barriers and socioeconomic, health care system, disease,
and therapy-related factors.10 In patients under
statin therapy, adverse effects were the leading cause for statin
discontinuation in a previous study, reporting that 25% of statin users
believed statins cause memory loss,11 a rare and
inconsistent finding in the literature.12,13Furthermore, Ahmed ST et al. reported that physicians preferred to avoid
explaining all potential adverse effects to patients as it could
influence their medication-taking behavior.14Conversely, Rodriguez F et al. observed that patient preference was a
higher determinant for statin withdrawal than adverse
effects.9 This result does parallel with ours, leading
to the suggestion that suboptimal health literacy may account for a
significant proportion of nonadherence, reflecting an inadequate
doctor-patient relationship. In this regard, a study found statin safety
and risks concerns were the main reason for withdrawal, and those
nonadherent were more skeptical of having a higher risk of myocardial
infarction and stroke with high cholesterol levels than their adherent
counterparts.11 Thus, effective communication and
education on the natural history of disease and treatment
characteristics might be needed to clarify patients’ concerns and
demystify statin impact on CVD. Moreover, clinicians should promote
adherence by encouraging a higher patient-physician involvement,
potentially ameliorating therapy misconceptions, and decreasing patient
misinterpretations about their condition, henceforth decreasing
nonadherence. In this framework, a significant trend toward statin
treatment reinitiation willingness (59.7%) was observed in those
patients who discontinued statins after dialogue with their
doctor.11
In the current study, forgetfulness accounted for the most prevalent
cause of nonadherence (53.5%), likely exposing underlying prescription
complexities beyond medication-taking behavior such as multi-drug
regimen, different dosing times, blood pressure, and glucose
self-tracking, and lifestyle modifications.15 In this
sense, polypill implementation could offer potential advantages over
conventional pharmacotherapy as it provides an easy-to-remember
monotherapy regimen. Multiple studies have reported the
cost-effectiveness of a polypill strategy for secondary prevention of
CVD, observing an increase in adherence rate, reduction in CVD
burden,16-18 and dose titration.19Nonetheless, their clinical employment in diverse populations might be
hampered by healthcare systems and socioeconomic disparities across
countries. Although some randomized clinical trials in developing
countries 17,20 and underserved populations in the
United States16 demonstrated its cost-efficacy, drug
prices need to be reduced to improve access, availability, and
affordability in these countries.21,22 Hence, polypill
strategy might be challenging in low- and middle-income countries owing
to higher out-of-pocket costs than conventional pills. In this context,
limited access to care, medication costs, and low socioeconomic status
might account for poor adherence in low- and middle-income countries, as
observed in this study, where 24% of the patients reported drug
discontinuation for economic factors. Likewise, although forgetfulness
might play a role in some patients, particularly in those with mild
cognitive impairment and aging patients, underlying causes such as
personal indifference to well-being, low self-esteem, suboptimal health
literacy, age misconception, absence of family support, polypharmacy,
and depression should also be considered as they may contribute to this
phenomenon as well. Early decline and suboptimal adherence in such
patients could be prevented by frequent communication and assessment of
patients’ environment and psychosocial and cognitive status,
particularly in patients with clinical and subclinical depression.
Even though physician-related barriers were the less prevalent (1.2%)
in our study, lipid-lowering guidelines’ misunderstanding might also
account for poor adherence, leading to suboptimal risk reduction in
those who may benefit from high-intensity therapy.23 A
previous study observed higher adherence patterns in patients taking
moderate-intensity statin therapy than patients on low-intensity or
high-intensity statin regimens.9 While, Khunti K et
al. found that patients receiving high-intensity therapy were the more
adherent group.24According to a study, stable LDL-C
levels or at goal was the most prevalent cause reported by 42% of
physicians for treating patients with a lower statin intensity than
recommended.25 Consistently, statin therapy
discontinuation by physicians was observed in a large proportion of
patients with adverse effects after the index event, receiving a
lipid-lowering drug alternative in only 2.6% of the
cases.25 Moreover, high to moderate adherence has
shown to lead to more significant reductions in total cholesterol and
LDL-C levels than statin discontinuation and/ or
withdrawal.26 These findings could explain our
observations as higher cholesterol, triglycerides, and hemoglobin A1c
levels were found in those patients with inadequate adherence. In such
patients, physicians might seek to maintain a high to moderate statin
regimen in order to reduce overall atherosclerotic cardiovascular
disease (ASCVD) risk and improve medication-taking behavior, as patients
seem to be more conscious of the importance of medication adherence and
disease control.
Furthermore, the number of consultations and the level of care might
also impact secondary prevention therapy adherence. In a study performed
at the Veterans Affairs system, a higher adherence was observed in those
with regular primary care physician (PCP) control, reporting adherence
improvement in those patients with at least one visit compared to those
without any consultation.27 Rehman H et al. found that
patients under cardiology control had 9% higher odds of being more
adherent in comparison with those under primary care
management.28 This finding seems to differ markedly
from ours as the National Institute of Cardiology ”Ignacio Chávez” is
one of the highest accredited healthcare organizations in Cardiology in
Mexico. However, it is worth mentioning that most of the patients do not
have any further medical control and depend solely on their annual
Cardiology consultation at the institute. In this understanding, the low
adherence found in the institute could portray the country’s health care
scenario. Therefore, it could be hypothesized that adherence to statins
and renin-angiotensin-aldosterone system blockers, and potentially other
medications, might be more severe in other country institutions.
Further analysis observed that low school level and optimal medical
therapy (OMT) without revascularization were independent predictors for
nonadherence. In such patients, an invasive approach by
revascularization or coronary artery bypass graft surgery (CABG) may
account for a proper adherence pattern, likely behaving as a placebo.
Likewise, these patients may be more knowledgeable about their disease
and nonadherence potential consequences as opposed to those under OMT
alone, exhibiting more adequate adherence patterns. This discrepancy
could be attributed to patient misconception on their condition and
medication unawareness due to chronic diseases’ asymptomatic and slowly
progressive nature and the lack of short-term clinical evidence of
medication administration benefits. From this perspective, nonadherence
may arise from ineffective implementation tools of intensive
pharmacologic and lifestyle intervention, disclosing current approach
failure and the need for strategies reassessment to impel more valuable
and efficient enforcement methods. In this sense, whether the initial
strategy should be conservative or interventional is still a matter of
open-ended debate. Although multiple trials have been conducted to
compare the effectiveness of OMT with and without percutaneous coronary
intervention (PCI) on cardiovascular mortality, nonfatal MI, and
all-cause mortality reduction, none has shown a difference between
groups.29,30 In contrast with these conclusions,
observational studies have reported lower mortality and cardiac deaths
in the PCI arm.31 This disagreement could be
attributed to the closed control observed in randomized clinical trials,
potentially conferring a predictive model with ideal characteristics
which might not represent a real-world setting. Therefore, when
superimposed these observations with our findings, it could be
hypothesized that observational studies demonstrated better outcomes
with invasive strategies by better reflecting real-world variabilities
such as medication adherence. Henceforth in order for the OMT to achieve
the results observed in clinical trials, it might be necessary to
generate effective patient-based adherence strategies.
On the other hand, low school level was the most important predictor for
nonadherence. The odds of nonadherence were 2.37 times higher in those
patients with elementary school or less, finding similar results to
previously documented in a former study.23 This
finding could potentially explain adherence rate discrepancies observed
with high-income countries, and it could be extrapolated to other low-
and middle-income countries as well, reflecting the complex
interrelation of economic burden and medication-taking behavior. Hence,
medication nonadherence may compel all institutions to develop
population-based adherence instruments to address the problem in an
integral manner since the spectrum of adherence seems to overcome
cultural and ethnic barriers. Besides, adherence might differ among
institutions. Measuring adherence data as a quantitative analysis could
probably be of limited value. Thus, a new method should be implemented
to measure this complex parameter, in which case screening tools could
be used to identify high-risk persons on the basis of all five
nonadherence-related factors and clinical prediction algorithms.
Nonetheless, more data is needed to evaluate these hypotheses, and a
properly designed multicenter registry study must be conducted to
complement these results with a representative sample of Mexico.
In this area of high unmet medical need, these findings should raise
concern among physicians as nonadherence can lead to suboptimal risk
reduction in high-risk populations, negatively impacting not only
patients’ quality of life and survival rate but also increasing direct
and indirect health care system costs. Consistently, these findings
could provide incremental value to promote interdisciplinary units and
develop patient-centered health policies to improve patients’ quality of
life and survival rate in high-risk populations to attenuate the CVD
burden. Thus, new and targeted specific population-based strategies are
needed to improve the current adherence situation in the country.