What is the diagnosis and treatment for Familial Hypercholesterolemia (FH)?

From the Guidelines

Familial hyperlipidemia should be managed with a combination of lifestyle modifications and medications, prioritizing statins as first-line therapy, to reduce the risk of premature cardiovascular disease, as recommended by the most recent guidance from the International Atherosclerosis Society 1. The management of familial hyperlipidemia involves a multifaceted approach, including:

• Lifestyle modifications:
  • Heart-healthy diet low in saturated fats and cholesterol
  • Regular exercise
  • Maintaining a healthy weight
  • Avoiding smoking
• Medication therapy:
  • First-line: statins, such as atorvastatin (20-80 mg daily) or rosuvastatin (10-40 mg daily), which reduce LDL cholesterol by inhibiting cholesterol synthesis in the liver
  • Additional medications for severe cases or those not responding adequately to statins:
    • Ezetimibe (10 mg daily), which decreases intestinal cholesterol absorption
    • PCSK9 inhibitors, such as evolocumab or alirocumab, administered as subcutaneous injections every 2-4 weeks
    • Bile acid sequestrants
    • Other options, such as bempedoic acid, inclisiran, or LDL apheresis, may be considered in specific patient groups, as outlined in the 2022 ACC expert consensus decision pathway 1 Regular monitoring of lipid levels is essential, typically every 3-6 months initially and then annually once stable, to ensure optimal management and reduce the risk of premature cardiovascular disease. Early diagnosis and treatment are crucial, as untreated familial hyperlipidemia significantly increases the risk of premature cardiovascular disease, including heart attacks and strokes, due to accelerated atherosclerosis from lifelong exposure to elevated lipid levels, highlighting the importance of implementation strategies to increase the impact of clinical recommendations on the care of patients with familial hypercholesterolaemia 1.

From the FDA Drug Label

As an adjunct to diet to reduce low-density lipoprotein cholesterol (LDL-C) in: Adults with primary hyperlipidemia Adults and pediatric patients aged 10 years and older with heterozygous familial hypercholesterolemia (HeFH).

The recommended starting dosage of atorvastatin calcium is 10 mg to 20 mg once daily. The dosage range is 10 mg to 80 mg once daily. Patients who require reduction in LDL-C greater than 45% may be started at 40 mg once daily.

Familial Hyperlipidemia Treatment with Atorvastatin:

• Atorvastatin is indicated for the treatment of heterozygous familial hypercholesterolemia (HeFH) in adults and pediatric patients aged 10 years and older.
• The recommended starting dosage is 10 mg to 20 mg once daily, with a dosage range of 10 mg to 80 mg once daily.
• Atorvastatin can be used as an adjunct to diet to reduce low-density lipoprotein cholesterol (LDL-C) in patients with HeFH.
• Patients who require a reduction in LDL-C greater than 45% may be started at 40 mg once daily 2, 2.

From the Research

Definition and Characteristics of Familial Hyperlipidemia

• Familial hypercholesterolemia (FH) is a genetic disorder of lipid metabolism characterized by a significant elevation in levels of low-density lipoprotein cholesterol (LDL-C) 3
• The etiology of FH includes known mutations in the gene of the LDL receptor, LDLR; the gene of apolipoprotein B, apo B; and the proprotein convertase subtilisin/kexin type 9 gene, PCSK9 3
• Patients with FH are at very high risk for premature coronary heart disease (CHD) 3

Diagnosis and Screening

• Early identification and aggressive treatment of FH in individual patients, as well as screening of all first-degree relatives, are recommended to minimize the risk for premature CHD 3
• Current guidelines recommend LDL-C targets for FH (either heterozygotes [HeFH] or homozygotes [HoFH]) <100 mg/dL (<2.6 mmol/L) for adults or <70 mg/dL (<1.8 mmol/L) for adults with CHD or diabetes, and <135 mg/dL (<3.5 mmol/L) for children 4

Treatment Options

• Patients with FH should receive statins as initial treatment, but patients with FH may require higher doses of statins, more potent statins, statin-based combination therapy, or adjunctive therapies 3
• Novel drug therapies that target the pathophysiologic defects of the condition are continuously emerging, including mipomersen, lomitapide, and PCSK9 inhibitors 5
• Combinations of cholesterol-lowering therapies are often used to lower LDL-cholesterol in patients with FH; however, current treatment goals for LDL-cholesterol are rarely achieved in patients with homozygous FH (HoFH) and are difficult to achieve in patients with heterozygous FH (HeFH) 6

Treatment Outcomes

• LDL cholesterol reduction ranged from 30.2 ± 17.0% with simvastatin 10 mg to 48.2 ± 14.7% with rosuvastatin 40 mg in patients with HeFH 7
• A suboptimal response (<15% or <30% reduction in LDL cholesterol levels, respectively with low-/moderate-intensity and high-intensity statin therapy) was observed in 13.5% and, respectively, 20.3% of the subjects with HeFH 7
• The ranking for more to less potent statins was rosuvastatin, atorvastatin and simvastatin; however, at maximum dosage, atorvastatin and rosuvastatin were nearly equivalent 7