What is Familial Hypercholesterolemia (FH)?

From the Guidelines

Familial hypercholesterolemia patients should be treated with a combination of lifestyle modifications and high-intensity statins as the first-line treatment, with the goal of achieving a ≥50% LDL-C reduction from baseline LDL-C, as recommended by the most recent guidelines 1. The treatment of familial hypercholesterolemia (FH) typically involves a combination of lifestyle modifications and medications. Patients should start with a low-cholesterol diet, regular exercise, and avoidance of smoking. For medication, high-intensity statins are the first-line treatment, such as atorvastatin 40-80 mg daily or rosuvastatin 20-40 mg daily, as they have been shown to reduce the risk of clinical coronary heart disease and coronary heart disease mortality in patients with FH 1. If LDL cholesterol targets aren't achieved with statins alone, ezetimibe 10 mg daily can be added, as it has been shown to provide additional LDL-C lowering in patients with FH 1. For severe cases or those not responding to these medications, PCSK9 inhibitors like evolocumab (140 mg every 2 weeks) or alirocumab (75-150 mg every 2 weeks) may be prescribed, as they have been shown to provide significant additional LDL-C lowering in patients with FH 1. Some key points to consider in the treatment of FH include:

• Early screening and diagnosis, typically by age 10, and may require medication by age 8-10 if their LDL levels remain high 1
• The use of a treatment algorithm to guide the management of patients with FH, including the use of statins, ezetimibe, and PCSK9 inhibitors 1
• The importance of achieving a ≥50% LDL-C reduction from baseline LDL-C, as recommended by the most recent guidelines 1
• The need for regular monitoring and adjustment of treatment to ensure that patients with FH achieve and maintain their LDL-C targets, as well as to minimize the risk of adverse effects 1

From the Research

Definition and Diagnosis of Familial Hypercholesterolemia

• Familial hypercholesterolemia (FH) is a genetic disorder characterized by elevated low-density lipoprotein (LDL)-cholesterol (LDL-C) levels and early onset of atherosclerotic cardiovascular disease 2.
• The disorder is caused by mutations in genes that regulate LDL catabolism, mainly the LDL receptor (LDLR), apolipoprotein B (APOB), and gain of function of proprotein convertase subtilisin kexin type 9 (PCSK9) 2.
• Different clinical diagnosis criteria are available, and the cost of genetic testing has been reduced in recent years 3.

Treatment and Management of Familial Hypercholesterolemia

• Patients with FH are at high cardiovascular risk, and the risk can be reduced with lifelong lifestyle and pharmacological treatment 3.
• Statins and ezetimibe are available as generic drugs in most countries, reducing the cost of treatment 3.
• High-dose, high-potency statins are the mainstay for LDL-C lowering in FH, but often, these medications are not enough to reduce cholesterol to adequate levels, and ezetimibe and PCSK9 inhibitors may also be necessary 2.
• Current guidelines recommend LDL-C targets for FH, and with the pharmacological options available, these targets can be achieved in the majority of heterozygous FH subjects 4.

Importance of Early Treatment and Screening

• Early screening to identify and subsequently treat children with familial hypercholesterolemia is crucial to reduce the risk of premature atherosclerotic cardiovascular disease (ASCVD) 5.
• Screening in childhood and early initiation of optimal lipid-lowering therapy (LLT) have shown promising outcomes in the prevention of ASCVD 5.
• Children with familial hypercholesterolemia benefit from early detection and optimal treatment of their elevated LDL-C levels 5.

Comparison of Treatments

• A study comparing rosuvastatin and atorvastatin in patients with heterozygous familial hypercholesterolemia found that rosuvastatin produced a significantly greater reduction in LDL cholesterol than atorvastatin 6.
• Rosuvastatin also produced significantly greater increases in high-density lipoprotein (HDL) cholesterol and enabled more patients to achieve LDL cholesterol goals 6.