*4.1.8 Symptomatic peripheral artery disease (PAD)*

Patients with PAD being never on statins had a significantly higher mortality rate (31%) than those being continuous on statins (13%) or being new on statins (8%;

*P* < 0.0001) or on intensified statins (9%). Those who terminated statin medication or reduced statin dosage had higher mortality (34% and 20%, respectively; *P* < 0.0001) [56].

#### **4.2 Economic outcomes**

The cost-effectiveness of optimal adherence to the guidelines was commonly assessed by calculating the incremental cost-effectiveness ratio (ICER), representing the discrepancies in costs between the intervention and control groups divided by the discrepancies in effectiveness between both groups (Eq. (1)) [57]. Effectiveness is commonly expressed as quality-adjusted life years (QALY), combining quality and quantity of life. Whether optimal adherence can be considered cost-effective relies on a community's affordability for one QALY. The lower the ICER, the more the cost-effectiveness. To define the ICER cutoff point, the WHO proposed using the per capita gross domestic product (GDP) [58]. An intervention must cost less than once the national annual GDP per capita per QALY to be highly cost-effective. An intervention must cost less than three times the national annual GDP per capita per QALY to be considered cost-effective:

$$\text{ICER} = \frac{\text{Cost}\_{\text{interaction}} - \text{Cost}\_{\text{control}}}{\text{Effectiveness}\_{\text{interaction}} - \text{Effectiveness}\_{\text{control}}} \tag{1}$$

For primary prevention, adherence was predicted to be more cost-effective in patients with a higher 10-year risk for a cardiovascular event in a study across 13 European countries. The risk was calculated from a risk score tool and included males, age >65 years, smoking, HTN, diabetes, hypercholesterolemia, and history of CVD. Adherence to the European guidelines on CVD prevention (e.g. smoking cessation medication, BP-lowering medication, and cholesterol-lowering medication) was used as an intervention. A base case ICER of 52,968€/QALY over 10 years was estimated for patients with an average baseline risk of 20%. Considering high-risk patients (≥20%), the ICER was reduced to 29,093€/QALY with decreasing ICERs in higherrisk patients. Patients with higher-risk reductions (≥0.5%) were also associated with lower ICERs [59]. Another study evaluating the cost-effectiveness of enhancing adherence to antihypertension medications indicated that enhancing adherence from 52% (the baseline) to 70% and 80% resulted in a reduced ICER from €76,484 (95% CI €74,807–€78,152) to €75,055 (95% CI €73,490–€76,623) and €73,605 (95% CI €72,180–€75,157), respectively, for each hospitalization for a MACE prevented. This aligns with the previous findings based on a large database (*n* = 625,620). Mean annual healthcare costs were estimated to be lower for patients with 80–100% adherence to antihypertensive medications (\$7182) than for those with 60–79% adherence (\$7560) and <60% adherence (\$7995) (*P* < 0.001 for both) [57].

For secondary prevention, in the post-MI population, optimal adherence (≥80%) had lower per-patient annual medical costs for hospitalizations of \$369 and \$440 compared with suboptimal adherence (≥40–≤79%), and nonadherence (<40%), respectively. In the ASCVD subgroup, optimal adherence had lower per-patient annual medical costs for hospitalizations of \$371 and \$907 than suboptimal adherence and nonadherence [42]. Another study in India found positive findings that adherence (80% or lower) to aspirin and BBs was highly cost-effective. The additional *Medication Adherence in Cardiovascular Diseases DOI: http://dx.doi.org/10.5772/intechopen.108181*

ACEIs were cost-effective, based on Indian gross domestic product per capita [60]. In patients discharged with ACS, those adhering to medications, outpatient controls, and rehabilitation had lower costs for medications (€199 per year) and higher costs for outpatient controls and rehabilitation (€292 and €1024) compared with those who did not [61]. An Australian secondary prevention program for CVD (i.e. optimizing medication use and lifestyle modification) was found to produce an ICER of AUD 8081 per disability-adjusted life year (DALY) prevented, which is well below the acceptable benchmark of AUD 50,000 per DALY within the Australian healthcare system [13].

In chronic vascular diseases, enhancing medication adherence increased medication costs but produced medical savings by reducing hospitalization. An American study in 224,231 patients with risk for CVD indicated that adherents' average annual medication costs were \$1058 more for those with congestive HF, \$429 more for HTN, \$656 more for diabetes, and \$601 more for hypercholesterolemia as compared with non-adherents. In contrast, adherence lowered mean annual medical costs by \$8881 in congestive HF, \$4337 in HTN, \$4413 in diabetes, and \$1860 in hypercholesterolemia [62].

In sum, higher adherence to medications to treat CVD was associated with higher medication costs but lower nonmedication medical costs, reducing overall healthcare costs. Health economic models were estimates based on available evidence and several assumptions. Interpreting the results thus needs to be cautious when applying these models in the health policy decision-making process.
