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Life sciences · Journal article
American Journal of Preventive Cardiology · July 28, 2026
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The smallest worthwhile difference (SWD) - the minimum absolute benefit required to justify a treatment against its burdens - varies by personal preference. We investigated factors associated with SWD variation for statin therapy in primary prevention of atherosclerotic cardiovascular disease (ASCVD) to inform shared decision-making strategies. This pre-planned secondary analysis used survey data from the US (n = 602) and Japan (n = 665). Participants determined their SWD for statins across three 10-year ASCVD risk scenarios (2%, 10%, 20%) using the Benefit-Harm Trade-off Method. Subgroup analyses compared SWD by statin use history, self-perceived baseline risk, and hypercholesterolemia diagnosis. Associations between participant characteristics and SWD were examined using proportional odds regression adjusted for age and sex. A post hoc analysis using a directed acyclic graph explored the causal role of prior cholesterol education. The median SWD exceeded the benefits typically provided by statins across all scenarios. Predictors of lower SWDs (greater willingness to initiate statins) were mostly consistent across countries. Higher self-perceived ASCVD risk was associated with lower SWD: in the moderate-risk scenario, median SWDs decreased from 7.5-10.0% to 2.5-5.0% as self-perceived risk increased. Current statin use, hypercholesterolemia history, and cardiovascular comorbidities were each associated with lower SWDs. After adjusting for confounders, prior cholesterol education was associated with 38% (US) and 47% (Japan) lower odds of selecting a higher SWD (OR 0.62 [95%CI 0.42-0.90] and 0.53 [0.31-0.90], respectively), indicating lower treatment efficacy expectations. Risk perception and understanding of treatment benefits may predict statin acceptance. Educational interventions strengthening treatment-specific knowledge may represent a promising strategy to align patient preferences with clinical evidence.