Abstract Body (Do not enter title and authors here): Introduction
Cumulative exposure to elevated low-density lipoprotein cholesterol (LDL-C) in young adulthood (ages 18-39) increases later life atherosclerotic cardiovascular disease risk. Statins are cost-effective in young adults with LDL-C ≥130 mg/dL. However, current guidelines only recommend statins for LDL-C ≥190 mg/dL. Some young adults may not achieve treatment goals with statin monotherapy and additional lipid-lowering therapy may be cost-effective, especially given the advent of generic pricing for ezetimibe and reduced pricing for PCSK9 inhibitors (PCSK9-Is).

Objective
We aimed to estimate the cost-effectiveness of statins with supplemental ezetimibe and supplemental PCSK9-Is in US young adults with LDL-C ≥130 mg/dL.

Methods
The CVD Policy Model, an established computer simulation model, calculated the lifetime costs and quality-adjusted life years (QALYs) of lipid-lowering therapy. Analyses were stratified by pretreatment LDL-C and the model accounted for cumulative LDL-C exposure in young adulthood. Treatment costs and effects were derived from published literature and publicly available data. Results were presented as incremental cost-effectiveness ratios (ICERs) and categorized as highly cost-effective (<$50,000/QALY), intermediately cost-effective ($50,000-$150,000/QALY), and not cost-effective (>$150,000/QALY).

Results
Compared with no treatment, statin plus ezetimibe therapy was highly cost-effective for young adults with LDL-C ≥160 mg/dL (ICER: $33,200/QALY; Table) and intermediately cost-effective for young adults with LDL-C ≥130 mg/dL (ICER: $67,100/QALY). Statin plus PCSK9-I therapy substantially increased QALYs but was not cost-effective in any subgroup. To be intermediately cost-effective for young adults with LDL-C ≥190 mg/dL, PCSK9-I prices would need to be reduced by 80%.

Conclusion
With generic pricing, statin plus ezetimibe therapy is highly cost-effective for young adults with elevated LDL-C. Large price reductions are required for statins plus PCSK9-Is to be cost-effective.