GUIDELINE
RECOMENDATIONS3

Assessment for cardiovascular
disease (CVD) risk

Systematic global CVD risk assessment is recommended to guide treatment decision-making. Individuals with FH are at high- or very-high risk of CVD. To improve risk assessment, the use of imaging techniques to detect asymptomatic atherosclerosis is recommended.

Very high risk
High risk

FH patients with

  • atherosclerotic cardiovascular disease (ASCVD) or

  • another major risk factor such as a calculated SCORE ≥ 10% for 10-year risk of fatal CVD, DM with target organ damage, etc.

FH patients without other risk factors

LDL-C goals

The 2019 ESC/EAS Dyslipidemia Guidelines recommends to reduce LDL-C to as
low a level as possible

Very high risk
High risk

LDL-C < 55 mg/dL
AND
≥ 50% LDL-C reduction from baseline*

LDL-C < 70 mg/dL
AND
≥ 50% LDL-C reduction from baseline*

* Baseline refers to the LDL-C level in a person not taking any lipid-lowering therapy or to the extrapolated baseline value for those who are on current treatment.

TREATMENT OPTIONS

FH management is composed of non-pharmacological and pharmacological elements.

Non-pharmacological: dietary, lifestyle modifications and smoking cessation2

Systematic global CVD risk assessment is recommended to guide treatment decision-making. Individuals with FH are at high- or very-high risk of CVD. To improve risk assessment, the use of imaging techniques to detect asymptomatic atherosclerosis is recommended.

Lifestyle interventions to
reduce LDL-C level 3
Magnitude of the effect
Avoid dietary trans fats
Reduce dietary saturated fats
Increase dietary fibre
Use functional foods enriched with phytosterols
Use red yeast rice nutraceuticals
Reduce excessive body weight
Reduce dietary cholesterol
Increase habitual physical activity

Some food choices to help lower LDL-C and improve the overall lipid profile

  • Wholegrains
  • Vegetables
  • Legumes
    (lentils, beans, fava
    beans, peas, chickpeas,
    soybean)
  • Fresh or frozen fruit
  • Lean and oily fish,
    poultry without skin
  • Skimmed milk and
    yoghurt
  • Vinegar, mustard,
    fat-free dressings
FH management is composed of pharmacological and non-pharmacological elements.

LDL-C lowering mechanisms.4,5

Evinacumab

Promotes VLDL processing and clearance upstream of LDL formation

Lomitapide

Inhibits synthesis of chylomicrons and VLDL and leads to decreased LDL-C

Statins

Interfere with HMG-CoA reductase, the critical enzyme in the biosynthesis of cholesterol

Bempedoic acid

ACL inhibitor; inhibits cholesterol synthesis in the liver; increases LDL receptor density

Inclisiran

siRNA targeting PCSK9; inhibits PCSK9 production in liver, thereby prolonging activity of LDL receptors

PCSK9 mAb (alirocumab, evolocumab)

Binds to PCSK9 and increases the number of LDL receptors available to clear circulating LDL-C

Bile acid resins

Bind bile acids, thus increasing the excretion of cholesterol in the stool

Ezetimibe

Blocks the
absorption of
cholesterol from the
small intestine

Cholesterol-lowering treatment should be initiated as soon as possible after a diagnosis has been made. Treatment should be initiated with high-intensity statin therapy, in most cases in combination with ezetimibe.3,5
HeFH3,5-7
HoFH2,3,5,7-9
Children withFH3,6,8,9
Treatment goal
Very high risk

LDL-C < 55 mg/dL
AND
≥ 50% LDL-C reduction from baseline*

High risk

LDL-C < 70 mg/dL
AND
≥ 50% LDL-C reduction from baseline*

LDL-C <135 mg/dL
at >10 years of age

Statins

Recommended
(often in combination with ezetimibe)

Recommended
(often in combination with ezetimibe)

Recommended(start from age 8 to 10 as long as proved safe for children)

Should be started with low doses and the dose should be increased to reach goals

Non statin therapies:
1st consider ezetimibe and/or PCSK9 mAbs
2nd May consider bempedoic acid or inclisiran
3rd May consider evinacumab, lomitapide and/or lipoprotein apheresis

Ezetimibe

Recommended
(often in combination with statin)

Recommended
(often in combination with statin)

PCSK9 mAbs*

If

  • The treatment goal is not achieved on maximal tolerated statin plus ezetimibe for very-high-risk patients
  • FH patients who cannot tolerate statin

Consider PCSK9 inhibitor with or without apheresis PCSK9 inhibitor is not recommended in patients with LDLR-/- mutations (LDLR activity < 2%)

According to ACC
2023 expert
consensus,
Recommend PCSK9
(evolucumab) in
patients ≥ 10 years
with HeFH as an
adjunct to diet and
other LDL-C lowering
therapies

Other

May consider bempedoic acid or inclisiran5

May consider evinacumab, lomitapide, and/or lipoprotein apheresis for HoFH under care of lipid specialist5

HeFH: ezetimibe, bile
acid-binding resin

HoFH: lipoprotein
apheresis (by age 5
and not later than 8
years)

* PCSK9 mAbs5: alirocumab and evolocumab

REFERENCES:
  1. Ison HE, et al. Familial Hypercholesterolemia. 2014 Jan 2 [Updated 2022 Jul 7]. In: GeneReviews®. Seattle (WA): University of Washington, Seattle. Available from: https://www.ncbi.nlm.nih.gov/books/NBK174884/
  2. Lui DTW, et al. Management of Familial Hypercholesterolemia: Current Status and Future Perspectives. J Endocr Soc. 2020;5(1):bvaa122.
  3. Mach F, et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J. 2020;41(1):111-188.
  4. Nurmohamed NS, et al. New and Emerging Therapies for Reduction of LDL-Cholesterol and Apolipoprotein B: JACC Focus Seminar 1/4. J Am Coll Cardiol. 2021;77(12):1564-1575.
  5. Writing Committee; et al. 2022 ACC Expert Consensus Decision Pathway on the Role of Nonstatin Therapies for LDL-Cholesterol Lowering in the Management of Atherosclerotic Cardiovascular Disease Risk: A Report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol. 2022;80(14):1366-1418.
  6. Catapano AL, et al. 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias: The Task Force for the Management of Dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS) Developed with the special contribution of the European Assocciation for Cardiovascular Prevention & Rehabilitation (EACPR). Atherosclerosis. 2016;253:281-344.
  7. Landmesser U, et al. European Society of Cardiology/European Atherosclerosis Society Task Force consensus statement on proprotein convertase subtilisin/kexin type 9 inhibitors: practical guidance for use in patients at very high cardiovascular risk. Eur Heart J. 2017;38(29):2245-2255.
  8. Cuchel M, et al. 2023 Update on European Atherosclerosis Society Consensus Statement on Homozygous Familial Hypercholesterolaemia: new treatments and clinical guidance. Eur Heart J. 2023;44(25):2277-9
  9. Nordestgaard BG et al. Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease: consensus statement of the European Atherosclerosis Society. Eur Heart J. 2013; 34:3478a-3490a.