**4. Costs associated with non-adherence**

With the increase of life expectancy, the greater the spending on health. Accord-ing to an OECD study, people over 65 accounts for 40–50% of health spending in Europe and their per capita costs are 3–5 times higher than those under 65. And, this tends to increase over time [28].

There are not many researches that investigate the impact of non-adherence on the economy, since it is difficult to assess. In addition to the direct impact on both patient health and nonadherence healthcare costs such as avoidable hospitalizations, emergencies, drugs, and so on, non-adherence leads to an indirect impact on the economy. In fact, per year, non-adherence leads to an average of 2.62 days that the employee missed work, leading to a decrease in the productivity [29]. Moreover, few articles focus on the costs of non-adherence among the elderly. The following paragraphs review the costs of non-adherence in several diseases that often affect the elderly such as chronic cardiovascular diseases, chronic obstructive pulmonary disease, diabetes, arthritis, and osteoporosis.

Will et al., in 2016, found that hospitalizations were eight times more frequent in non-adherent hypertension patients. Expenditures with these patients were four times higher compared to adherent patients. According to the author's estimates, in the United States of America, the outcome of non-adherence was \$ 41 million, over 3 million for non-adherent hypertensive patients, over a period of 8 years. These costs were related to the cost of outpatient medication and preventable hospitalizations [30].

Bansilal et al., in 2016, studied the association between the levels of adherence and longterm major adverse cardiovascular events and resource utilization in coronary artery disease patients. The authors found that non-adherent patients have higher associated medical costs, with \$ 719 associated with hospitalizations per patient and \$ 821 associated with revascularization surgeries, being these patients also related to higher emergency visits. Thus, it is possible to deduce that non-adherence to treatments, in addition to the risk to the patient, leads to increases in expenses associated with secondary cardiac events [31].

In congestive heart failure, Esposito et al., in 2009, assessed the impact that adherence to therapy would have on the related costs in patients with congestive heart failure. Non-adherent patients (17,496 compared to 19,122 adherent patients) had higher costs for the health system (US\$ 25,312 compared to US\$ 19,402 for adherent patients), mainly explained by the increase in hospital admissions (42% of the total value), in terms of higher frequency/duration compared to adherent patients [32].

The characteristics of the disease such as severity and the symptomatic/asymptomatic nature are factors related to the condition that affects adherence. It is considered that the severity of the disease and the disability that symptoms cause at physical, psychological and social levels are most frequently associated with non-adherence. Individuals with chronic asymptomatic diseases do not adhere to treatment frequently, since the absence of symptoms lower their motivation to take their drugs continuously. In addition, the existence of other concomitant diseases that are treated with various medications (i.e., polypharmacy) is also one of the major

With the increase of life expectancy, the greater the spending on health. Accord-ing to an OECD study, people over 65 accounts for 40–50% of health spending in Europe and their per capita costs are 3–5 times higher than those under 65. And, this tends to increase over

There are not many researches that investigate the impact of non-adherence on the economy, since it is difficult to assess. In addition to the direct impact on both patient health and nonadherence healthcare costs such as avoidable hospitalizations, emergencies, drugs, and so on, non-adherence leads to an indirect impact on the economy. In fact, per year, non-adherence leads to an average of 2.62 days that the employee missed work, leading to a decrease in the productivity [29]. Moreover, few articles focus on the costs of non-adherence among the elderly. The following paragraphs review the costs of non-adherence in several diseases that often affect the elderly such as chronic cardiovascular diseases, chronic obstructive pulmonary

Will et al., in 2016, found that hospitalizations were eight times more frequent in non-adherent hypertension patients. Expenditures with these patients were four times higher compared to adherent patients. According to the author's estimates, in the United States of America, the outcome of non-adherence was \$ 41 million, over 3 million for non-adherent hypertensive patients, over a period of 8 years. These costs were related to the cost of outpatient medication

Bansilal et al., in 2016, studied the association between the levels of adherence and longterm major adverse cardiovascular events and resource utilization in coronary artery disease patients. The authors found that non-adherent patients have higher associated medical costs, with \$ 719 associated with hospitalizations per patient and \$ 821 associated with revascularization surgeries, being these patients also related to higher emergency visits. Thus, it is possible to deduce that non-adherence to treatments, in addition to the risk to the patient, leads

In congestive heart failure, Esposito et al., in 2009, assessed the impact that adherence to therapy would have on the related costs in patients with congestive heart failure. Non-adherent patients (17,496 compared to 19,122 adherent patients) had higher costs for the health system (US\$ 25,312

to increases in expenses associated with secondary cardiac events [31].

factors that contribute to non-adherence [17, 25, 27].

**4. Costs associated with non-adherence**

disease, diabetes, arthritis, and osteoporosis.

and preventable hospitalizations [30].

time [28].

32 Gerontology

Simoni-Watilla et al., in 2012, demonstrated that adherent patients with chronic obstructive pulmonary disease had higher costs related to prescription medications than non-adherent patients. However, these were cost-effective since the adherent patients have much lower costs than the non-adherent patients, in terms of hospitalizations and outpatient [33]. Halpern et al., in 2011, drew the same conclusions. Although pharmacy costs were higher in adherent patients, non-adherent patients incurred higher total expenditures [34].

Ho et al., in 2006, evaluated the impact of non-adherence in Type 2 Diabetes. Higher HbA<sup>1</sup> c, blood pressure and LDL cholesterol levels were recorded in non-adherent patients, leading to the increased risk of mortality and morbidity. The economic impact of non-adherence is continually increasing, resulting in long-term complications [35]. Dall et al., in 2010, estimated that \$ 218 billion per year (indirect costs spent for treating diabetes) spent in the USA. Although the cost of treating diabetes is high, representing approximately 7% of health spending, the return on this investment is enormous. Per year, non-insulin and non-antihyperglycemic drugs, insulin and oral hyperglycemic agents cost \$ 776, while avoidable hospitalizations cost \$ 886 per patient [36].

Tang et al., in 2008, found that arthritis adherent patients have higher costs in the pharmacy than non-adherent patients. However, costs related to outpatient, inpatient and laboratory services, related to non-adherence, exceed the amount spent in the pharmacy [37]. Pasma et al., in 2017, demonstrated that decreased adherence leads to an increase in healthcare costs (in anti-TNF therapies, synthetic DMARDs and rheumatology outpatients) [38].

In osteoporosis, poor adherence reduces the potential effectiveness of the drug, resulting in decreased health outcomes and incurring heavy costs. Hiligsmann et al., in 2009 evaluated the economic outcome of non-adherence in osteoporosis patients. Non-adherent patients suffer from more fractures than adherent patients, leading to higher healthcare spending, in comparison to the costs associated with medication adherence [39].

In general, all adherent patients have higher drug costs for obvious reasons. However, in the long run, they incur lower expenses than the non-adherent patients, since visits to the emergency rooms, inpatient and outpatient are decreased [40]. One of the reasons that lead the elderly to non-adherence is the high price of medicines. For pensioners with poor retirement, they must manage the budget to pay for basic needs, being in the medicines no longer a priority [41]. One of the ways to overcome this problem is to increase support for the elderly in the purchase of medicines or to reduce their taxes. Although this will mean higher expenses initially, it will pay off in the long-term [42].
