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Introduction: Individuals with no established cardiovascular disease (CVD) are currently recommended preventive statin therapy based on 10-year absolute risk (AR) of CVD, and individuals with a 10-year AR ≥7.5% are recommended statins. However, individuals with elevated LDL cholesterol experience greater absolute CVD absolute risk reduction (ARR) from statin therapy compared with those with the same 10-year AR but with lower LDL. A previous study showed that ARR-based statin treatment would prevent more CVD events than AR-based treatment in the 10 years following treatment initiation.Objective: This study aimed to quantify the long-term benefits of treating patients based on ARR rather than AR.Methods: A microsimulation version of the CVD Policy Model, a decision-analytic state transition model, simulated intermediate-strength statin therapy in 40,000 CVD-free US adults (50% female) under a variety of treatment strategies. The model predicts health outcomes for individuals based on their age, sex, and risk factor profile, accounting for the competing risk of non-CVD mortality. Individuals entered the model aged 40 years, and a time horizon of 40 years was employed. Life year gains and CVD events prevented compared to no treatment were estimated for a range of 10-year ARR and AR treatment initiation thresholds.Results: At the same numbers of patient-years of treatment (PYoT), ARR consistently produced more life year gains than AR (Figure). A 10-year ARR threshold of ≥2.62% would lead to approximately the same PYoT as standard of care (10-year AR ≥7.5%) while preventing 60 additional CVD events and producing 421 additional life year gains in the cohort.Conclusion: Treating patients with statins based on ARR would yield significant health gains in the U.S. population compared to standard AR-based treatment strategies. The ARR strategy may also achieve greater adherence and uptake as it focuses on individuals with elevated levels of a modifiable risk factor.