Several new non-statin agents have LDL cholesterol-lowering efficacy and can be considered for patients at risk for atherosclerotic cardiovascular disease (ASCVD), according to an expert consensus decision pathway published in the Journal of the American College of Cardiology. Donald M. Lloyd-Jones, MD, and colleagues provide practical guidance for clinicians and patients in situations not covered by the 2018 AHA/ACC/ multi-society cholesterol guideline. The authors offer algorithms that assume that all patients are in one of four evidence-based management groups: adults aged 20 or older with clinical ASCVD on statin therapy for secondary prevention; adults with primary severe hypercholesterolemia; and those with and without diabetes receiving statins for primary prevention of ASCVD. Factors that should be considered in terms of management include adherence to lifestyle modifications and evidence-based, guideline-recommended statin treatment; risk-enhancing factors; control of risk factors; the potential benefits and potential harms; and patient reference with respect to the addition of non-statin therapies. Optional interventions that can be considered include referral to a lipid specialist and registered dietician, ezetimibe, bile acid sequestrants, proprotein convertase subtilisin/kexin type 9 monoclonal antibodies, bempedoic acid, and inclisiran.