Synopsis Adults 40 to 75 years of age in primary prevention can be classified as borderline risk (10-year risk of ASCVD and high-risk (20%). For intermediate-risk patients, moderate- to high-intensity statin therapy should be considered during risk discussion of treatment options. Additional considerations favoring use of statins in in- termediate-risk patients include other independent risk conditions and, in selected individuals, risk-enhancing factors associated with greater ASCVD risk (Table 6). Although the variability of percent LDL-C lowering with high-intensity statin use is wide, its efficacy is proportional to the magnitude of the LDL-C reduction Systematic reviews indicate that those with higher baseline ASCVD risk derive greater absolute benefit from higher percent LDL-C reduction with evi- Accordingly, if a statin is given, LDL-C levels should be reduced by 30% and optimally by 50%. When there is uncertainty, consid- eration of risk-enhancing factors including family his- tory of premature ASCVD and CAC score, categorical risk factors, and selected biomarkers may inform the decision. CAC scoring is especially useful in older adults to improve specificity.S4.4.2-15 A CAC score of zero revises ASCVD risk downward and selects adults who show reduced benefit from starting a statin.S4.4.2-20 Recommendation-Specific Supportive Text 1. Prior guidelines recommended moderate- or high- intensity statins as first-line LDL-C lowering ther- apy in primary prevention of ASCVD after a risk discussion of treatment options. This was based on 3 large-scale exclusively primary-prevention RCTs that demonstrated that moderate-intensity and high-intensity statin were associated with ASCVD risk reduction that outweighed the observable risks. Since those ACC/AHA 2013 guidelines, a large- scale RCT in a racially/ethnically diverse population confirmed statin benefit from a moderate-inten- sity dose of a statin as compared with placebo in intermediate-risk patients. 