What is the recommended LDL (Low-Density Lipoprotein) target for patients with familial hyperlipidemia?

LDL Cholesterol Targets for Familial Hyperlipidemia

For patients with familial hyperlipidemia, the recommended LDL-cholesterol target is <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

Risk Stratification in Familial Hyperlipidemia

• All patients with familial hypercholesterolemia (FH) must be recognized as high-risk patients and require aggressive lipid-lowering therapy. 1
• FH should be suspected in patients with CHD before the age of 55 years for men and 60 years for women, in subjects with relatives with premature fatal or non-fatal CVD, 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)]. 1
• Family cascade screening is recommended when an index case of FH is diagnosed. 1

LDL-C Treatment Goals Based on Risk Category

Very High-Risk FH Patients

• 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. 1
• If this target cannot be reached, a reduction of at least 50% from baseline LDL-C is recommended as an alternative goal. 1
• For patients with previous ASCVD events, an even lower target of <1.4 mmol/L (<55 mg/dL) should be considered. 1

High-Risk FH Patients

• For FH patients at high cardiovascular risk without ASCVD, an LDL-C goal of <2.6 mmol/L (<100 mg/dL) is recommended. 1
• If baseline LDL-C is between 2.6 and 5.2 mmol/L (100 and 200 mg/dL), a reduction of at least 50% is recommended as an alternative goal. 1
• An LDL-C goal of <2.5 mmol/L (<100 mg/dL) may be considered in patients with additional risk factors for ASCVD. 1

Moderate-Risk FH Patients

• For FH patients at moderate risk, an LDL-C goal of <3.0 mmol/L (<115 mg/dL) is recommended. 1

Children with FH

• In children with FH, an LDL-C goal of <3.5 mmol/L (<135 mg/dL) is recommended. 1, 2

Treatment Approach to Achieve LDL-C Goals

First-Line Therapy

• High-intensity statins are the first-line therapy for FH patients and should be initiated at the highest recommended or tolerated dose. 1
• FH patients should be treated with intense-dose statin, often in combination with ezetimibe. 1

Second-Line Therapy

• If LDL-C goals are not achieved with maximum tolerated statin therapy, ezetimibe should be added. 1, 3
• Bile acid sequestrants may also be considered as additional therapy. 1

Third-Line Therapy

• For patients who do not achieve LDL-C goals with statin and ezetimibe, PCSK9 inhibitors should be considered. 1, 3
• In the highest-risk patients (those with symptomatic ASCVD or multivessel coronary atherosclerosis), the combination of a high-potency statin, ezetimibe, and PCSK9-targeted therapy should be strongly considered as first-line treatment. 1

Severe Cases

• For homozygous FH patients or those with markedly elevated LDL-C levels despite conventional therapy, lipoprotein apheresis, lomitapide (a microsomal triglyceride transfer protein inhibitor), or evinacumab (an angiopoietin-related protein 3 inhibitor) should be considered. 1

Monitoring and Follow-up

• LDL-C levels should be monitored regularly to assess treatment efficacy and adjust therapy as needed. 1
• Both fasting and non-fasting blood samples may be used to monitor LDL-C levels in those receiving stable therapy. 1
• Growth and adherence to lifestyle management and LDL-C-lowering medication should be monitored annually or as clinically indicated in pediatric patients. 1

Clinical Benefits of Achieving LDL-C Goals

• Achieving the recommended LDL-C targets significantly reduces cardiovascular events in FH patients. 3, 2
• Early diagnosis and appropriate treatment can lower the risk of atherosclerosis in heterozygous patients to that of the general population. 2
• Evidence suggests that 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. 4

Common Pitfalls and Caveats

• FH is largely underdiagnosed and undertreated despite the availability of effective therapies. 3, 2
• Some FH patients, particularly those with familial combined hyperlipidemia, may have small, dense LDL particles that are resistant to statin therapy alone, necessitating combination therapy for optimal results. 5
• Therapeutic lifestyle changes remain essential in clinical management for all FH patients regardless of LDL-C level. 4
• Adolescent girls with FH should be offered advice regarding contraception and the use of lipid-lowering medications in pregnancy. 1