Based on randomized trial subgroup analyses, further LDL-C lowering with ezetimibe or a PCSK9 mAb appears to provide the a meaningful clinical benefit when baseline LDL-C levels are <100 mg/dl only in the extremely high risk ASCVD patients ≥4% risk of ASCVD per year, eg those with an extensive burden of atherosclerosis as well as multiple comorbidities or heterozygous familial hypercholesterolemia. Here, PCSK9 is linked to familial hypercholesterolemia.