From the Guidelines
The American Heart Association (AHA) and American College of Cardiology (ACC) guidelines for treating familial hypercholesterolemia (FH) recommend aggressive LDL-cholesterol lowering therapy, with high-intensity statins as first-line treatment, as stated in the international atherosclerosis society guidance for implementing best practice in the care of familial hypercholesterolaemia 1.
Treatment Approach
For heterozygous FH, treatment should begin with maximum tolerated statin therapy, with a goal of reducing LDL-C by at least 50% from baseline. If LDL-C remains above 100 mg/dL (or 70 mg/dL for those with clinical atherosclerotic cardiovascular disease), ezetimibe 10 mg daily should be added. For patients not achieving target LDL-C levels with statins and ezetimibe, PCSK9 inhibitors (evolocumab or alirocumab) are recommended 1.
Homozygous FH Treatment
Homozygous FH requires more aggressive treatment, often including LDL apheresis, lomitapide, or evinacumab. Treatment should begin early, with statins recommended from age 2 years for children with homozygous FH, and ideally by the age of 2 years, with counselling on heart-healthy lifestyles, psychological support for the family and LDL-cholesterol-lowering medications 1.
Lipoprotein Apheresis
Lipoprotein apheresis should be undertaken, if feasible, in children (aged ≥3 years and <8 years) and adults with HoFH who do not achieve guideline-recommended LDL-cholesterol goals, despite maximally tolerated, combination drug therapy 1.
Key Recommendations
- Treatment of patients with HoFH should begin at diagnosis and ideally by the age of 2 years, with counselling on heart-healthy lifestyles, psychological support for the family and LDL-cholesterol-lowering medications 1.
- The following treatment goals should be considered: (a) LDL-cholesterol concentration <2.5 mmol/l (<100 mg/dl) in the absence of ASCVD or other major risk factors for ASCVD; (b) LDL-cholesterol concentration <1.8 mmol/l (<70 mg/dl) with imaging evidence of ASCVD alone or additional major risk factors for ASCVD; (c) LDL-cholesterol concentration <1.4 mmol/l (<55 mg/dl) with a previous ASCVD event 1.
- To achieve LDL-cholesterol goals, all currently approved medications (such as high-potency statin, ezetimibe and colesevelam) should be used; medications should be used sequentially, starting with a statin with rapid up-titration to maximally tolerated and approved doses, followed within 8 weeks by the addition of ezetimibe and possibly colesevelam if tolerated 1.
From the FDA Drug Label
To reduce the risk of myocardial infarction, stroke, and unstable angina requiring hospitalization in adults with established cardiovascular disease. As an adjunct to diet, alone or in combination with other low density lipoprotein cholesterol (LDL-C)-lowering therapies, in adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia (HeFH), to reduce LDL-C. As an adjunct to other LDL-C-lowering therapies in adult patients with homozygous familial hypercholesterolemia (HoFH) to reduce LDL-C. As an adjunct to diet and other LDL-C-lowering therapies in pediatric patients aged 8 years and older with HeFH to reduce LDL-C.
The American Heart Association (AHA) and American College of Cardiology (ACC) guidelines for treating familial hypercholesterolemia (FH) recommend the following:
- LDL-C reduction: The primary goal of treatment is to reduce LDL-C levels.
- Pharmacotherapy: Alirocumab (SQ) 2, rosuvastatin (PO) 3, and atorvastatin (PO) 4 are indicated as adjuncts to diet for the treatment of heterozygous familial hypercholesterolemia (HeFH) and homozygous familial hypercholesterolemia (HoFH).
- Treatment approach: Treatment should be individualized based on the patient's risk factors, LDL-C levels, and response to therapy.
From the Research
American Heart Association and American College of Cardiology Guidelines for Treating Familial Hypercholesterolemia
The American Heart Association (AHA) and American College of Cardiology (ACC) provide guidelines for the treatment of familial hypercholesterolemia (FH), a genetic condition characterized by high levels of low-density lipoprotein cholesterol (LDL-C) and increased risk of cardiovascular disease.
- The 2013 ACC/AHA guidelines emphasize the importance of identifying patients with FH, initiating high-intensity statin therapy, and monitoring lipid levels to assess treatment efficacy and compliance 5.
- Statins are the first-line therapy for lowering LDL-C in FH, particularly in heterozygous patients, and are safe for use in children and adolescents with FH 6.
- The guidelines also recommend the use of non-statin drugs, such as ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, when needed to achieve optimal LDL-C levels 7, 8.
- PCSK9 inhibitors, such as alirocumab and evolocumab, have been shown to reduce LDL-C levels by 50-60% in patients with heterozygous FH, allowing many to achieve their LDL-C goals 7.
- Inclisiran, a long-acting small interfering RNA therapeutic agent, has also been shown to reduce LDL-C levels by more than 50% for at least 6 months in patients with FH 7.
Treatment Options for Heterozygous and Homozygous FH
- For heterozygous FH, statin therapy is often combined with ezetimibe and/or PCSK9 inhibitors to achieve optimal LDL-C levels 8, 6.
- For homozygous FH, treatment options may include statins, ezetimibe, PCSK9 inhibitors, and other lipid-lowering therapies, such as mipomersen and lomitapide 8, 9.
- Rosuvastatin has been shown to be effective in reducing LDL-C levels in children with homozygous FH, with a mean reduction of 22.3% 9.
Importance of Early Treatment and Genetic Mutations
- Early treatment of FH is crucial to prevent cardiovascular disease, and statin therapy should be initiated as soon as possible after diagnosis 6.
- The effectiveness of treatment may depend on the underlying genetic mutations, with patients having 2 defective LDL receptor mutations tend to have a better response to statin therapy than those with 2 negative LDL receptor mutations 9.