Introduction

Advances in diagnostic and therapeutic strategies have improved ischemic heart disease (IHD) outcomes over the last decades¹. Particularly, the use of evidence-based pharmacological therapy has been demonstrated to improve long-term prognosis by reducing mortality by up to 40%, stabilizing disease progression, reducing the risk of recurrence, and enhancing functional capacity². Nonetheless, despite these advancements, IHD remains the leading cause of morbidity and mortality in countries of all income groups³, reflecting the suboptimal implementation of secondary prevention strategies and the subsequent burden on global health-care services. The use of such medications is still low, with a non-adherence prevalence ranging from 40 to 80%⁴, exhibiting health disparities among countries and socioeconomic status³. In this context, most available data on medication adherence proceeds from developed countries and clinical trials⁵, which may not reflect the actual situation of developing countries, especially in those with higher income health inequalities. Thus, medication-taking behavior may require national consensus and individualized tools to address the problem in a population-based manner to overcome socioeconomic, cultural, and ethnic barriers. Although data exist on medication adherence for secondary prevention of cardiovascular disease (CVD) in developing countries, to the best of our knowledge, no study has explored potential reasons for non-adherence in Mexico. This study aimed to determine the level of adherence to secondary prevention therapy in patients with IHD in the National Institute of Cardiology Ignacio Chávez and identify the key barriers contributing to medication non-adherence.

Materials and methods

Results

Discussion

The present study assessed the adherence level to secondary cardiovascular prevention therapy in a large public inner-city health center. Three significant conclusions were made from this analysis. First, < 30% of patients with IHD were entirely adherent to their prescribed secondary prevention medications at our institution. Second, when barriers to non-adherence were evaluated, 86.9% were due to patient-related factors, showing statistical significance. Third, individuals with less than a middle school education and those on optimal medical therapy (OMT) only had a higher inadequate adherence risk than those with higher educational attainment – regardless of socioeconomic status, age, occupation, or NYHA functional class. These findings should raise concern among clinicians as these patients are at higher risk of recurrent CVD, and related hospitalization and mortality⁸. Previous evidence has demonstrated that secondary preventive medication reduces CVD morbidity and mortality by over 40%. However, these benefits are hampered by inadequate adherence patterns, increasing annual health-care costs by up to 18%².

When comparing our adherence level with studies carried out in other countries, there are significant discrepancies, especially those documented in high-income countries such as the United States, where adherence rates range between 50% and 87%⁹,¹⁰. However, suboptimal adherence complexity surpasses gross national income, as our prevalence rate was highly concordant with those previously reported in Taiwan¹¹, a high-income country. These extensive dissimilarities seem to exhibit the underlying intricacy of the problem and why slight to no progress has been made in the last decades.

Non-adherence arises from the interplay between patient-related barriers and socioeconomic, health-care system, disease, and therapy-related factors¹². Nonetheless, the most common motives for inadequate adherence in our study were patient-related, reflecting an insufficient understanding of the disease and poor decision-making among these patients. Thus, suboptimal health literacy may account for a substantial problem in our population, potentially explaining the low adequate adherence rate observed. Moreover, low health literacy has been associated with poor health outcomes, increasing health-care costs, and worsening quality of life, particularly in vulnerable populations¹³. Early decline and suboptimal adherence in such patients could be prevented by efficient communication to assess patients’ environment and psychosocial and cognitive status, along with patient education on disease aspects to clarify concerns and demystify medication impact on CVD¹⁴.

Among inadequate adherence factors, forgetfulness counted for the most prevalent cause, likely exposing underlying prescription complexities beyond medication-taking behavior, such as multi-drug regimens, different dosing times, blood pressure and glucose self-tracking, and lifestyle modifications. 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 burden¹⁵-¹⁷, and dose titration¹⁸. Nonetheless, their clinical employment in diverse populations might be limited by health-care systems and socioeconomic disparities across countries. Although some randomized clinical trials in developing countries¹⁶,¹⁹ and underserved populations in the United States¹⁵ demonstrated its cost-efficacy, drug prices need to be reduced to improve access, availability, and affordability in these countries²⁰. This suggests that a polypill strategy might be challenging in low- and middle-income countries owing to higher out-of-pocket costs than conventional pills. Hence, limited access to care, medication costs, and low socioeconomic status might account for poor adherence in these countries, as observed in this study, where 24% of the patients reported drug discontinuation for economic motives. Moreover, although forgetfulness might play a role in some 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. The encouragement of higher patient-physician involvement could ameliorate these factors by reducing therapy misconceptions and decreasing patient misinterpretations about their condition, henceforth decreasing poor health literacy, and enhancing adherence.

The number of consultations and the level of care might also play a role in the adherence of these patients, as a higher rate has been observed in those with regular primary care physician control, reporting an adherence improvement in those receiving at least one visit in comparison to those without any consultation²¹. Moreover, patients under cardiology control had 9% higher odds of being more adherent in comparison with those under primary care management²². However, this finding seems to differ markedly from ours, as our institution is one of the highest accredited health-care organizations in Cardiology in Mexico. Nonetheless, it is worth mentioning that most of the patients do not have any further medical control and depend solely on their annual consultation at the institute. In this understanding, it could be hypothesized that the level of 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 a low school level and OMT without revascularization were independent predictors for non-adherence. In such patients, an invasive approach by revascularization or coronary artery bypass graft surgery may account for a proper adherence pattern, likely behaving as a placebo, as they might be more knowledgeable about their disease and non-adherence potential consequences as opposed to those under OMT alone. This discrepancy could be attributed to patient misconceptions of 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, non-adherence 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 methods¹³,¹⁵.

Although multiple trials have been conducted to compare the effectiveness of OMT with and without PCI on cardiovascular mortality, non-fatal MI, and all-cause mortality reduction, none has shown a difference between groups. In contrast with these conclusions, observational studies have reported lower mortality and cardiac deaths in the PCI arm²³. 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 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 non-adherence. The odds of non-adherence were 2.37 times higher in those patients with elementary school or less, finding similar results to those previously documented in a former study²⁴. This finding could potentially explain adherence rate discrepancies observed in 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 non-adherence 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. A new method should be implemented to measure this complex parameter, in which screening tools could be used to identify high-risk persons based on all five non-adherence-related factors and clinical prediction algorithms.

In this area of high unmet medical need, these findings should raise concern among physicians as non-adherence 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 conclusion, in patients with IHD and pharmacological therapy for secondary prevention, inadequate adherence is observed in 70%. The factors associated with poor pharmacological adherence were low educational level and the prescription of medical treatment without revascularization. Our study is one of the first to evaluate this problem in the Mexican population and includes a representative population. These results should generate concern in health systems, emphasizing the need to develop strategies to solve this problem.