OBJECTIVES: A recent World Heart Federation guideline described the benefit of reducing cumulative exposure to low-density lipoprotein cholesterol (LDL-C) on the lifetime risk of atherosclerotic cardiovascular disease (ASCVD) events. Using a cumulative LDL-C-based modelling approach, we estimate the effect of a theoretical prevention program (PP) in Estonia to reduce LDL-C. Outcomes were incidence of ASCVD events and costs.

METHODS: A Markov cohort model was developed to estimate the incidence and costs of fatal and non-fatal myocardial infarction (MI) and ischemic stroke (IS) among cohorts aged 30-39, 40-49, 50-59, 60-69, and 70-79 years. We compared the standard of care (SoC) to a PP which results in all individuals achieving an LDL-C target of 1.4 mmol/L. Individuals were followed until 100 years of age. Baseline LDL-C was derived from a representative Estonian survey and individuals were categorized into four risk groups using LDL-C target recommendations by the European Society of Cardiology. First-ever MI and IS incidence for SoC were derived from Global Burden of Disease data and published studies from Estonia and Finland. The rate ratio applied to the risk of ASCVD events for the PP arm was based on the cumulative LDL-C difference. ASCVD management costs were based on Estonian Health Insurance Fund records and discounted at 5% annually.

RESULTS: The proportional reductions generated by the PP in ASCVD events were 82%, 77%, 70%, 58%, and 46% and proportional reductions in discounted ASCVD management costs were 65%, 59%, 53%, 46%, and 37%, respectively, in the five age cohorts detailed above. Results were sensitive to the compliance rate to the PP. Risk reduction estimates are corroborated by primary prevention outcomes in Finland observed over 40 years.

CONCLUSIONS: The cumulative LDL-C modelling approach indicates that reducing LDL-C in younger adults may substantially reduce ASCVD events and management costs, and to a greater degree than previous modelling approaches.