What is the treatment for familial hypercholesterolemia (high cholesterol due to genetic disorder)?

Treatment of Familial Hypercholesterolemia

The treatment of familial hypercholesterolemia (FH) requires maximally tolerated high-potency statins (such as atorvastatin, rosuvastatin, or pitavastatin) combined with ezetimibe and/or bempedoic acid, along with a fat-modified, heart-healthy diet as the initial approach for most patients to achieve LDL-cholesterol goals. 1

Stepwise Treatment Approach

First-Line Therapy

• Maximally tolerated high-potency statins (atorvastatin, rosuvastatin, pitavastatin)
  • Starting dose of atorvastatin is typically 10-20 mg daily, with dosage range of 10-80 mg 2
  • For patients requiring >45% LDL-C reduction, starting at 40 mg daily may be appropriate 2
  • For pediatric patients (≥10 years) with HeFH, starting dose is 10 mg daily (range 10-20 mg) 2

Second-Line Therapy (if LDL-C goals not achieved)

• Add ezetimibe (reduces cholesterol absorption, lowers LDL-C by 18-25%) 3
• Consider bempedoic acid if available (provides additional 15-24% LDL-C reduction) 3

Third-Line Therapy

• Add PCSK9-targeted therapy (monoclonal antibodies or small interfering RNA) if LDL-C goals still not achieved
  • These agents reduce LDL-C by 40-65% 3
  • Examples include evolocumab (Repatha)

Additional Options

• Plant sterols/stanols or bile acid sequestrants (e.g., colesevelam) may be considered as adjunctive therapies 1
• For severe cases of homozygous FH, LDL apheresis may be required 4

Special Considerations

Extremely High-Risk HeFH Patients

For patients with extremely high-risk HeFH (e.g., after myocardial infarction or with multivessel coronary atherosclerosis), consider combination of high-potency statin, ezetimibe, and PCSK9-targeted therapy as first-line treatment 1

Pediatric Patients

• For children ≥10 years with HeFH, treatment approach is similar but with adjusted dosing
• Atorvastatin is approved for pediatric patients aged 10-17 years 2

Treatment Goals

LDL-C targets should be based on ASCVD risk level:

1. No ASCVD or major risk factors: LDL-C <2.5 mmol/L (<100 mg/dL)
2. Imaging evidence of ASCVD or major risk factors: LDL-C <1.8 mmol/L (<70 mg/dL)
3. Clinical ASCVD: LDL-C <1.4 mmol/L (<55 mg/dL)
4. Recurrent ASCVD event within 2 years on maximally tolerated statin: Consider lower goal of LDL-C <1.0 mmol/L (<40 mg/dL) 1

Monitoring

• Baseline liver enzymes, creatine kinase, glucose, and creatinine should be measured before starting therapy
• For stable patients, non-fasting lipid profiles can be used for monitoring
• When making treatment decisions, fasting LDL-C should be used, especially with concomitant hypertriglyceridemia 1
• Monitor liver enzymes in patients taking statins, particularly those with risk factors for hepatotoxicity
• Check creatine kinase if musculoskeletal symptoms develop 1

Lifestyle Modifications

All patients should receive counseling on:

• Fat-modified, heart-healthy diet
• Regular physical exercise
• Smoking cessation
• Management of other cardiovascular risk factors (hypertension, obesity, diabetes) 1

Family Screening

Cascade screening of family members is essential to identify additional cases of FH early and initiate appropriate treatment 3

By following this comprehensive approach to FH management, patients can achieve significant reductions in LDL-C levels and substantially lower their risk of premature cardiovascular disease.