LDL Cholesterol Targets for Familial Hyperlipidemia

Risk Stratification and Treatment Goals

The European Society of Cardiology recommends that all patients with familial hypercholesterolemia (FH) be recognized as high-risk patients and require aggressive lipid-lowering therapy, with an LDL-cholesterol target of <1.8 mmol/L (<70 mg/dL) or a reduction of at least 50% from baseline if the baseline LDL-C is between 1.8 and 3.5 mmol/L (70 and 135 mg/dL) 1, 2
FH should be suspected in patients with coronary heart disease before the age of 55 years for men and 60 years for women, in subjects with relatives with premature fatal or non-fatal cardiovascular disease, in subjects with relatives having tendon xanthomas, and in subjects with severely elevated LDL-C [in adults >5 mmol/L (190 mg/dL), in children >4 mmol/L (150 mg/dL)] [2]
Family cascade screening is recommended when an index case of FH is diagnosed, according to the European Heart Journal 2

For patients with FH who also have established atherosclerotic cardiovascular disease (ASCVD) or diabetes with target organ damage, an LDL-C goal of <1.8 mmol/L (<70 mg/dL) is recommended, as suggested by the European Heart Journal and Mayo Clinic Proceedings 1, 2
For patients with previous ASCVD events, an even lower target of <1.4 mmol/L (<55 mg/dL) should be considered, based on evidence from Nature Reviews Cardiology 4
For FH patients at high cardiovascular risk without ASCVD, an LDL-C goal of <2.6 mmol/L (<100 mg/dL) is recommended, according to the European Heart Journal 2, 3

High-intensity statins are the first-line therapy for FH patients and should be initiated at the highest recommended or tolerated dose, as recommended by the European Heart Journal and Nature Reviews Cardiology 2, 4
FH patients should be treated with intense-dose statin, often in combination with ezetimibe, according to the European Heart Journal 2
For patients who do not achieve LDL-C goals with statin and ezetimibe, PCSK9 inhibitors should be considered, as suggested by Nature Reviews Cardiology 4

LDL-C levels should be monitored regularly to assess treatment efficacy and adjust therapy as needed, according to the European Heart Journal 2
Both fasting and non-fasting blood samples may be used to monitor LDL-C levels in those receiving stable therapy, based on evidence from Nature Reviews Cardiology 4

Achieving the recommended LDL-C targets significantly reduces cardiovascular events in FH patients, although the exact mechanism is not fully understood, and additional benefit may be obtained by reducing LDL-C to substantially below 100 mg/dL, with no apparent threshold below which no further benefit is achieved, as reported by Praxis Medical Insights, but a similar recommendation is made by the European Heart Journal 2

Adolescent girls with FH should be offered advice regarding contraception and the use of lipid-lowering medications in pregnancy, as recommended by Nature Reviews Cardiology 4