They are at a very high risk of first and recurrent ASCVD events because of lifetime exposure to markedly elevated LDL-C levels. 10-year ASCVD risk assessment is not indicated in this high-risk population. ≥50% LDL-C reduction on maximal tolerated statin therapy and lifestyle modification are the initial goals.

Ezetimibe PCSK9 inhibitors as initial agent; addition of other as second agent, if needed. Cholesterol absorption inhibitors (ezetimibe) primarily ↓ LDL-C 10-18% ↓ Apo B 11-16%. In combination with statins, additional ↓ LDL-C 25%, total ↓ LDL-C 34-61%. PCSK9 inhibitors (alirocumab, evolocumab) ↓LDL-C 48-71%, ↓ non-HDL-C 49-58%, ↓ TC 36-42%, ↓ Apo B 42-55%.

In patients with familial hypercholesterolemia unresponsive to drugs and dietary management, lipid apheresis producing acute reduction in LDL-C performed weekly or biweekly should be considered. Lifestyle interventions with high level of evidence to reduce LDL-C and TC include reduction of dietary trans fats, saturated fats and increased intake of dietary fiber, functional foods enriched with phytosterols, red yeast rice supplements and reduction of excessive body weight.