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............................................................................................................................................................ increasing obesity, and diabetes560563 are the main contributors. CVD cost the European Union about e210 billion in 2015, one-half of which was in healthcare costs (8% of total healthcare expenditure), and the other half in productivity losses and informal care.558

In these Guidelines, the Joint Task Force recommends a range of actions to reduce CVD by targeting plasma lipids, ranging from population-wide initiatives to promote healthy lifestyles to individuallevel interventions to reduce CVD risk factors, such as unhealthy diets and high lipid levels. Cost-effectiveness analysis can help target resources for interventions where the net health gain is greatest in relation to the net resources, and is increasingly required across Europe.564 However, cost-effectiveness depends on available resources, the costs of services, and disease risk in the population, and results obtained in one country might not be valid in another.565 In addition, to fully capture the long-term effects of interventions, costeffectiveness studies combining evidence from RCTs with modelling and limitations in both could affect the reliability of findings. Here, the evidence for the cost-effectiveness of ASCVD preventive interventions with respect to lipid modification is summarized; further scrutiny in view of local circumstances is recommended. The health impact pyramid summarizes the evidence on the relative effort in relation to health impact (Figure 5), with interventions with the broadest impact on populations at the base and interventions requiring considerable individual effort at the top.566 There is consensus that all the levels of the pyramid should be targeted but that emphasis should be placed on the lower levels. This would address the persistent socio-economic divide in CV health despite major improvements in ASCVD treatment.558 More than one-half of the reduction in CV mortality over the last three decades has been attributed to population-level changes in CV risk factors, primarily reductions in plasma cholesterol, BP levels, and smoking.560563,567 Lifestyle changes at the population level may be more cost-effective than lifestyle and drug interventions at the individual level, particularly when targeted to populations at increased risk. Awareness and knowledge of how lifestyle risk factors lead to CVD has increased in recent decades. Moreover, legislation promoting a healthy lifestyle, such as reduced salt intake and smoking bans, has been reported to be cost-effective in preventing CVD,568573 and initiatives to improve infrastructure and promote physical activity have shown promise.574,575 A number of structural strategies at international, national, and regional levels combined can substantially reduce CVD morbidity and mortality.576,577 Individual-level interventions to improve diet,578,579 increase physical activity,580 and stop smoking581 could also be cost-effective.582 However, suboptimal adherence limits benefits,583,584 and interventions to improve adherence, such as electronic device reminders to reinforce favourable health behaviours, are increasingly being investigated.585

All statin regimens and ezetimibe are now generically available across Europe. There is strong evidence that lowering blood cholesterol levels using low-cost statins is widely cost-effective586590 in many categories of patients. For secondary prevention of CVD, the evidence suggests that statin treatments are highly cost-effective,586,590,591 and adding low-cost ezetimibe to high-intensity statin therapy further reduces LDL-C and CVD risk cost-effectively.592 In primary ASCVD prevention, the evidence indicates that generic statin-based treatments are cost-effective for people at least down to 1% annual total CVD risk and could be cost-effective at even lower risk,589 with the highest tolerated statin dose likely the most costeffective.591,593,594 Importantly, many patients on statin treatment fail to take their medications adequately and/or to reach their therapeutic goals,595 with clinical and economic consequences.596,597 Reinforcing measures aimed at improving adherence to treatment is cost-effective.598600 Studies have shown that at mid-2018 prices PCSK9 inhibitors were largely not cost-effective.601604 Their cost-effectiveness is improved in selected high-risk patients, such as those with clinical CVD or FH, other comorbidities, and high LDL-C levels.605,606 However, at lower prices, PCSK9 inhibitors would become costeffective in a wider range of high-risk patients; recent price reductions may therefore lead to increased use.607 Cost-effectiveness evidence for other lipid-modifying therapies is lacking. Effective interventions to prevent ASCVD, including statins, typically exhibit similar relative risk reductions across categories of patients, including by ASCVD risk; therefore, health benefits and cost-effectiveness are greater among people at higher ASCVD risk (Figure 6).36,233 Consequently, increased efforts and higher-intensity interventions should be aimed at individuals and populations at higher ASCVD risk.

Counseling and education

Clinical interventions

Long-lasting protective

interventions

Changing the context to make individuals' default decisions healthy

Socioeconomic factors

Increasing population

impact Increasing

individual effort needed

©ESC 2019

Figure 5 Health impact pyramid. Downloaded from academic.oup.com/eurheartj/article/41/1/111/5556353 by guest on 07 October 2026