What are the treatment options for familial hypercholesterolemia?

From the Guidelines

Treatment for familial hypercholesterolemia (FH) should start with high-intensity statins, and if necessary, be followed by the addition of ezetimibe, and for severe cases, PCSK9 inhibitors such as evolocumab or alirocumab, as these have been shown to significantly reduce LDL cholesterol levels and cardiovascular risk 1.

Key Treatment Options

• High-intensity statins like atorvastatin (40-80 mg daily) or rosuvastatin (20-40 mg daily) as first-line therapy
• Ezetimibe (10 mg daily) as a second-line agent for those not reaching target LDL levels with statins alone
• PCSK9 inhibitors such as evolocumab or alirocumab for patients with severe FH or those not reaching target LDL levels with statins and ezetimibe
• Bile acid sequestrants like cholestyrpol or colesevelam can also be considered
• Lifestyle modifications including a heart-healthy diet, regular exercise, weight management, smoking cessation, and limited alcohol consumption

Special Considerations

• For very severe cases, particularly homozygous FH, LDL apheresis may be necessary every 1-2 weeks 1
• Early treatment is crucial as FH patients have significantly elevated cardiovascular risk due to lifelong exposure to high LDL levels, which causes accelerated atherosclerosis
• Treatment should begin in childhood for those diagnosed early, and family screening is important since FH is an autosomal dominant genetic disorder

Recent Guidance

• The International Atherosclerosis Society guidance for implementing best practice in the care of familial hypercholesterolaemia emphasizes the importance of comprehensive care, including detection, diagnosis, genetic testing, and counseling, as well as management strategies that include risk stratification, treatment, and implementation strategies at the patient, provider, and health-care system levels 1

From the FDA Drug Label

To reduce the risk of: Myocardial infarction (MI), stroke, revascularization procedures, and angina in adults with multiple risk factors for coronary heart disease (CHD) but without clinically evident CHD As an adjunct to diet to reduce low-density lipoprotein (LDL-C) in: Adults with primary hyperlipidemia Adults and pediatric patients aged 10 years and older with heterozygous familial hypercholesterolemia (HeFH). As an adjunct to other LDL-C-lowering therapies to reduce LDL-C in adults and pediatric patients aged 10 years and older with homozygous familial hypercholesterolemia.

The treatment options for familial hypercholesterolemia include:

• Alirocumab (SQ): an injectable prescription medicine used to reduce low-density lipoprotein cholesterol (LDL-C) or bad cholesterol in adults with heterozygous familial hypercholesterolemia (HeFH) and homozygous familial hypercholesterolemia (HoFH) 2.
• Atorvastatin (PO): an HMG-CoA reductase inhibitor (statin) indicated as an adjunct to diet to reduce LDL-C in adults and pediatric patients aged 10 years and older with HeFH, and as an adjunct to other LDL-C-lowering therapies to reduce LDL-C in adults and pediatric patients aged 10 years and older with HoFH 3. Key points:
• The goal of treatment is to reduce LDL-C levels and prevent cardiovascular events.
• Treatment should be individualized based on the patient's specific needs and medical history.
• Patients with familial hypercholesterolemia may require ongoing monitoring and adjustment of their treatment plan to achieve optimal LDL-C levels.

From the Research

Treatment Options for Familial Hypercholesterolemia

• Statins are the first-line treatment for lowering low-density lipoprotein (LDL) cholesterol in familial hypercholesterolemia (FH), particularly in heterozygous patients 4
• High-potency statins at high doses are often required to achieve appropriate LDL-C lowering in patients with FH 5
• Additional treatments, such as ezetimibe, bile acid sequestrants, and PCSK9 inhibitors, may be necessary to achieve optimal LDL-C lowering in patients with FH 6, 7
• Novel drug therapies, including mipomersen, lomitapide, and alirocumab, are also available for the treatment of FH 5, 7
• Lipoprotein apheresis is indicated in homozygous FH or severe heterozygous FH patients with inadequate response to cholesterol-lowering therapies 8

Investigations for Familial Hypercholesterolemia

• Diagnosis of FH is often suspected in patients with elevated blood low-density lipoprotein cholesterol (LDL-C) levels 6
• The Dutch Lipid Clinical Criteria are a helpful diagnostic tool used to diagnose FH 6
• Genetic testing is available, but not widely used, to aid in the diagnosis of FH 8
• Cascade screening is recommended to identify affected family members 8

Management of Familial Hypercholesterolemia

• Early diagnosis and effective treatment can significantly improve prognosis in patients with FH 8
• Treatment strategy and target is currently based on low-density lipoprotein (LDL) cholesterol levels, as the prognosis of FH largely depends on the magnitude of LDL cholesterol-lowering that can be achieved by lipid-lowering therapies 8
• Combination of statins with ezetimibe and PCSK9 inhibitors significantly improves the efficacy of treatment 4
• Sustained long-term optimal statin treatment from an early age can effectively prevent atherosclerotic cardiovascular disease (ASCVD) over decades of life 4