The following guidance is based on the best available evidence. The full guideline gives details of the methods and the evidence used to develop the guidance.
Unless otherwise indicated, recommendations are relevant for people with possible or definite familial hypercholesterolaemia (FH). Recommendations are also applicable to people with heterozygous or homozygous FH, unless otherwise indicated.
See also section 1.4 on 'Information needs and support'.
1.1.1 Healthcare professionals should consider the possibility of FH in adults with raised cholesterol (total cholesterol typically greater than 7.5 mmol/l), especially when there is a personal or a family history of premature coronary heart disease.
1.1.2 Healthcare professionals should exclude secondary causes of hypercholesterolaemia before a diagnosis of FH is considered.
1.1.3 A diagnosis of FH should be made using the Simon Broome criteria, which include a combination of family history, clinical signs (specifically tendon xanthomata), cholesterol concentration and DNA testing (see appendix E of the NICE guideline).
1.1.4 Healthcare professionals should inform people with a diagnosis of FH based on the Simon Broome criteria (see appendix E of the NICE guideline) that they have a clinical diagnosis of FH.
1.1.5 Healthcare professionals should consider a clinical diagnosis of homozygous FH in adults with a low-density lipoprotein cholesterol (LDL-C) concentration greater than 13 mmol/l and in children/young people with an LDL-C concentration greater than 11 mmol/l. All people with a clinical diagnosis of homozygous FH should be offered referral to a specialist centre.
1.1.6 To confirm a diagnosis of FH, healthcare professionals should undertake two measurements of LDL-C concentration because biological and analytical variability occurs.
1.1.7 Healthcare professionals should be aware that the absence of clinical signs (for example, tendon xanthomata) in adults and children/young people does not exclude a diagnosis of FH.
1.1.8 A family history of premature coronary heart disease should always be assessed in a person being considered for a diagnosis of FH (see Simon Broome criteria in appendix E of the NICE guideline).
1.1.9 When considering a diagnosis of FH, healthcare professionals with expertise in FH should use standardised pedigree terminology to document, when possible, at least a three-generation pedigree. This should include relatives' age of onset of coronary heart disease, lipid concentrations and smoking history. For deceased relatives, the age and cause of death, and smoking history should be documented. If possible, the index individual should verify this information with other family members.
1.1.10 Ultrasonography of the Achilles tendon is not recommended in the diagnosis of FH.
1.1.11 Coronary heart disease risk estimation tools such as those based on the Framingham algorithm should not be used because people with FH are already at a high risk of premature coronary heart disease.
1.1.12 Healthcare professionals should offer people with a clinical diagnosis of FH a DNA test to increase the certainty of their diagnosis and to aid diagnosis among their relatives.
1.1.13 Healthcare professionals should inform all people who have an identified mutation diagnostic of FH that they have an unequivocal diagnosis of FH even if their LDL-C concentration does not meet the diagnostic criteria (see appendix E of the NICE guideline).
1.1.14 In a family where a DNA mutation is identified, not all family members may have inherited the mutation. When DNA testing has excluded FH in a member of a family, healthcare professionals should manage the person's coronary heart disease risk as in the general population.
1.1.15 In children at risk of FH because of one affected parent, the following diagnostic tests should be carried out by the age of 10 years or at the earliest opportunity thereafter.
A DNA test if the family mutation is known.
LDL-C concentration measurement if the family mutation is not known. When excluding a diagnosis of FH a further LDL-C measurement should be repeated after puberty because LDL-C concentrations change during puberty.
1.1.16 In children at risk of homozygous FH because of two affected parents or because of the presence of clinical signs, for example, cutaneous lipid deposits (xanthomata), LDL-C concentration should be measured before the age of 5 years or at the earliest opportunity thereafter. If the LDL-C concentration is greater than 11 mmol/l then a clinical diagnosis of homozygous FH should be considered.
1.2.1 Healthcare professionals should use systematic methods (that is, cascade testing) for the identification of people with FH.
1.2.2 Healthcare professionals should offer all people with FH a referral to a specialist with expertise in FH for confirmation of diagnosis and initiation of cascade testing.
1.2.3 Healthcare professionals with expertise in FH should explain what is meant by cascade testing, and discuss its implications with all people with FH.
1.2.4 Cascade testing using a combination of DNA testing and LDL-C concentration measurement is recommended to identify affected relatives of those index individuals with a clinical diagnosis of FH. This should include at least the first- and second- and, when possible, third-degree biological relatives.
1.2.5 In families in which a mutation has been identified, the mutation and not LDL-C concentration should be used to identify affected relatives. This should include at least the first- and second- and, when possible, third-degree biological relatives.
1.2.6 In the absence of a DNA diagnosis, cascade testing using LDL-C concentration measurements should be undertaken to identify people with FH.
1.2.7 To diagnose FH in relatives of an index individual, the gender- and age-specific criteria for LDL-C concentration in appendix E of the NICE guideline should be used. The Simon Broome LDL-C criteria for index individuals should not be used because this will result in under diagnosis.
1.2.8 The use of a nationwide, family-based, follow-up system is recommended to enable comprehensive identification of people affected by FH.
1.2.9 Healthcare professionals should be aware of the latest guidance on data protection when undertaking cascade testing.
22.214.171.124 When offering lipid-modifying drug therapy to adults with FH, healthcare professionals should inform the person that this treatment should be lifelong.
126.96.36.199 Statins should be the initial treatment for all adults with FH.
188.8.131.52 Healthcare professionals should consider prescribing a high-intensity statin to achieve a recommended reduction in LDL-C concentration of greater than 50% from baseline (that is, LDL-C concentration before treatment).
184.108.40.206 The dose of statin should be increased to the maximum licensed or tolerated dose to achieve a recommended reduction in LDL-C concentration of greater than 50% from baseline (that is, LDL-C concentration before treatment).
220.127.116.11 Healthcare professionals should offer treatment with a statin with a low acquisition cost for adults with FH in whom the diagnosis is made after the age of 60 and who do not have coronary heart disease.
18.104.22.168 Ezetimibe monotherapy is recommended as an option for treating primary heterozygous‑familial hypercholesterolaemia in adults in whom initial statin therapy is contraindicated.
22.214.171.124 Ezetimibe monotherapy is recommended as an option for treating primary heterozygous‑familial hypercholesterolaemia in adults who cannot tolerate statin therapy (as defined in recommendation 126.96.36.199).
188.8.131.52 Ezetimibe, co‑administered with initial statin therapy, is recommended as an option for treating primary (heterozygous‑familial) hypercholesterolaemia in adults who have started statin therapy when:
serum total or low‑density lipoprotein (LDL) cholesterol concentration is not appropriately controlled (as defined in recommendation 184.108.40.206) either after appropriate dose titration of initial statin therapy or because dose titration is limited by intolerance to the initial statin therapy (as defined in recommendation 220.127.116.11) and
a change from initial statin therapy to an alternative statin is being considered.
18.104.22.168 When prescribing ezetimibe co‑administered with a statin, ezetimibe should be prescribed on the basis of lowest acquisition cost.
22.214.171.124 For the purposes of this guidance, appropriate control of cholesterol concentrations should be based on individual risk assessment according to national guidance on managing cardiovascular disease in the relevant populations.
126.96.36.199 For the purposes of this guidance, intolerance to initial statin therapy is defined as the presence of clinically significant adverse effects that represent an unacceptable risk to the patient or that may reduce compliance with therapy.
188.8.131.52 Prescribing of drug therapy for adults with homozygous FH should be undertaken within a specialist centre.
184.108.40.206 Healthcare professionals should offer adults with FH a referral to a specialist with expertise in FH if treatment with the maximum tolerated dose of a high-intensity statin and ezetimibe does not achieve a recommended reduction in LDL-C concentration of greater than 50% from baseline (that is, LDL-C concentration before treatment).
220.127.116.11 Healthcare professionals should offer adults with FH a referral to a specialist with expertise in FH for consideration for further treatment if they are assessed to be at very high risk of a coronary event, that is, if they have any of the following.
Established coronary heart disease.
A family history of premature coronary heart disease.
Two or more other cardiovascular risk factors (for example, they are male, they smoke, or they have hypertension or diabetes).
18.104.22.168 Adults with FH with intolerance or contraindications to statins or ezetimibe should be offered a referral to a specialist with expertise in FH for consideration for treatment with either a bile acid sequestrant (resin), nicotinic acid, or a fibrate to reduce their LDL-C concentration.
22.214.171.124 The decision to offer treatment with a bile acid sequestrant (resin), nicotinic acid or a fibrate in addition to initial statin therapy should be taken by a specialist with expertise in FH.
126.96.36.199 Healthcare professionals should exercise caution when adding a fibrate or nicotinic acid to a statin because of the risk of muscle-related side effects (including rhabdomyolysis). Gemfibrozil and statins should not be used together.
188.8.131.52 Adults with FH who are prescribed nicotinic acid should be offered advice on strategies that reduce flushing. Such advice should include taking low initial doses with meals and/or aspirin 30 minutes before the first daily dose.
Children and young people
184.108.40.206 Healthcare professionals should offer all children and young people diagnosed with, or being investigated for, a diagnosis of FH a referral to a specialist with expertise in FH in children and young people. This should be in an appropriate child/young person-focused setting that meets the standards within the 'National service framework for children, young people and maternity services'.
220.127.116.11 Lipid-modifying drug therapy for a child or young person with FH should usually be considered by the age of 10 years. The decision to defer or offer lipid-modifying drug therapy for a child or young person should take into account:
the age of onset of coronary heart disease within the family, and
the presence of other cardiovascular risk factors, including their LDL-C concentration.
18.104.22.168 When offering lipid-modifying drug therapy for children or young people, healthcare professionals should inform the child/young person and their parent/carer that this treatment should be lifelong.
22.214.171.124 When the decision to initiate lipid-modifying drug therapy has been made in children and young people, statins should be the initial treatment. Healthcare professionals with expertise in FH in children and young people should choose a statin that is licensed for use in the appropriate age group.
126.96.36.199 Statin therapy for children and young people with FH should usually be prescribed at the doses specified in the 'British national formulary (BNF) for children'.
188.8.131.52 In exceptional instances, for example, when there is a family history of coronary heart disease in early adulthood, healthcare professionals with expertise in FH in children and young people should consider offering:
a higher dose of statin than is licensed for use in the appropriate age group, and/or
more than one lipid-modifying drug therapy, and/or
lipid-modifying drug therapy before the age of 10 years.
184.108.40.206 In children and young people with homozygous FH, LDL-C concentration may be lowered by lipid-modifying drug therapy and this should be considered before LDL apheresis (see section 1.3.3).
220.127.116.11 In children and young people with FH who are intolerant of statins, healthcare professionals should consider offering other lipid-modifying drug therapies capable of reducing LDL-C concentration (such as bile acid sequestrants [resins], fibrates or ezetimibe).
18.104.22.168 Routine monitoring of growth and pubertal development in children and young people with FH is recommended.
Adults and children/young people
22.214.171.124 Decisions about the choice of treatment should be made following discussion with the adult or child/young person and their parent/carer, and be informed by consideration of concomitant medication, comorbidities, safety and tolerability.
126.96.36.199 Healthcare professionals should consider offering fat-soluble vitamin (vitamins A, D and K) and folic acid supplementation for adults or children/young people with FH who are receiving long-term treatment with bile acid sequestrants (resins).
188.8.131.52 Healthcare professionals should offer people with FH a referral to a specialist with expertise in FH if they are experiencing side effects that compromise concordance with lipid-modifying drug therapy.
184.108.40.206 When the decision has been made to offer adults or children/young people with FH treatment with a statin, baseline liver and muscle enzymes (including transaminases and creatine kinase, respectively) should be measured before initiation of therapy. However, people with raised liver or muscle enzymes should not routinely be excluded from statin therapy.
220.127.116.11 Routine monitoring of creatine kinase is not recommended in asymptomatic adults or children/young people with FH who are receiving treatment with a statin.
18.104.22.168 Healthcare professionals should regard lifestyle advice as a component of medical management, and not as a substitute for lipid-modifying drug therapy.
22.214.171.124 All people with FH should be offered individualised nutritional advice from a healthcare professional with specific expertise in nutrition.
126.96.36.199 People with FH should be advised to consume a diet in which:
total fat intake is 30% or less of total energy intake
saturated fats are 10% or less of total energy intake
intake of dietary cholesterol is less than 300 mg/day
saturated fats are replaced by increasing the intake of monounsaturated and polyunsaturated fats.
It may be helpful to suggest they look at Live Well for further practical advice.
188.8.131.52 Healthcare professionals should advise people with FH to eat at least five portions of fruit and vegetables a day, in line with national guidance for the general population. Examples of what constitutes a portion can be found at Live Well.
184.108.40.206 Healthcare professionals should advise people with FH to consume at least two portions of fish a week (one of which should be oily fish). Pregnant women with FH should be advised to limit their oily fish to two portions a week. Further information and advice on healthy cooking methods can be found at Live Well.
220.127.116.11 Healthcare professionals should advise people with FH that if they wish to consume food products containing stanols and sterols these need to be taken consistently to be effective.
18.104.22.168 People with FH should not routinely be recommended to take omega-3 fatty acid supplements. For people with FH who have already had a myocardial infarction (MI), refer to 'MI: secondary prevention' (NICE guideline CG48).
22.214.171.124 Healthcare professionals should advise people with FH to take at least 30 minutes of physical activity a day, of at least moderate intensity, at least 5 days a week, in line with national guidance for the general population.
126.96.36.199 Healthcare professionals should encourage people with FH who are unable to perform moderate-intensity physical activity at least 5 days a week because of comorbidity, disability, medical conditions or personal circumstances to exercise at their maximum safe capacity.
188.8.131.52 Recommended types of physical activity include those that can be incorporated into everyday life, such as brisk walking, using stairs and cycling.
184.108.40.206 Healthcare professionals should advise people with FH that bouts of physical activity of 10 minutes or more accumulated throughout the day are as effective as longer sessions.
220.127.116.11 Healthcare professionals should offer people with FH who are overweight or obese appropriate advice and support to achieve and maintain a healthy weight in line with NICE guidance on obesity.
18.104.22.168 As for the general population, alcohol consumption for adult men with FH should be limited to up to 3–4 units a day, and for adult women with FH up to 2–3 units of alcohol a day. Binge drinking should be avoided. Further information can be found at Live Well.
22.214.171.124 People with FH, especially children, who do not smoke should be strongly discouraged from starting because of their already greatly increased risk of coronary heart disease.
126.96.36.199 People with FH who smoke should be advised that, because of their already greatly increased risk of coronary heart disease, they should stop.
188.8.131.52 Healthcare professionals should offer people who want to stop smoking support and advice, and referral to an intensive support service, in line with the NICE guidance on smoking cessation.
184.108.40.206 People with FH who are unwilling or unable to accept a referral to an intensive support service should be offered pharmacotherapy in line with NICE guidance on nicotine replacement therapy and bupropion, and varenicline.
220.127.116.11 Healthcare professionals should consider offering LDL apheresis for the treatment of adults and children/young people with homozygous FH (see recommendations 1.1.5 and 1.1.16). The timing of initiation of LDL apheresis should depend on factors such as the person's response to lipid-modifying drug therapy and presence of coronary heart disease.
18.104.22.168 In exceptional instances (such as when there is progressive, symptomatic coronary heart disease, despite maximal tolerated lipid-modifying drug therapy and optimal medical and surgical therapy), healthcare professionals should consider offering LDL apheresis for the treatment of people with heterozygous FH. This should take place in a specialist centre on a case-by-case basis and data recorded in an appropriate registry.
22.214.171.124 Healthcare professionals should recommend arterio-venous fistulae as the preferred method of access for people with FH who are offered treatment with LDL apheresis. People should be counselled about possible benefits and complications of this procedure.
126.96.36.199 Routine monitoring of the person's iron status should be carried out and iron supplementation initiated as required for people with FH who are receiving treatment with LDL apheresis.
188.8.131.52 Angiotensin-converting enzyme (ACE) inhibitors should not be used in people with FH who are being treated with LDL apheresis. Instead, ACE inhibitors should be substituted with angiotensin-receptor blocking agents.
184.108.40.206 People with FH who are receiving blood pressure-lowering drug therapy should have this reviewed and considered for discontinuation on the morning of the day of LDL apheresis.
220.127.116.11 People with FH who are taking warfarin should have this discontinued approximately 4 days before LDL apheresis and substituted with low molecular weight heparin.
18.104.22.168 People with FH who are receiving anti-platelet therapy should have this continued if they are receiving treatment with LDL apheresis.
22.214.171.124 Healthcare professionals should consider offering liver transplantation as an option for the treatment of people with homozygous FH after treatment with lipid-modifying drug therapy and LDL apheresis.
126.96.36.199 The decision to refer for liver transplantation should take place in partnership with the patient and/or their relatives in an appropriate specialist setting, following a discussion of the benefits and potential harms of undertaking or declining transplantation.
188.8.131.52 During the assessment and communication of familial risk, people should receive clear and appropriate educational information about FH, the process of family testing, DNA testing and the measurement of LDL-C concentration.
184.108.40.206 A healthcare professional with expertise in FH should provide information to people with FH on their specific level of risk of coronary heart disease, its implications for them and their families, lifestyle advice and treatment options.
220.127.116.11 Healthcare professionals with expertise in FH should encourage people with FH to contact their relatives to inform them of their potential risk and so that cascade testing can take place.
18.104.22.168 When considering cascade testing, a healthcare professional with expertise in FH should offer to facilitate the sharing of information about FH with family members.
22.214.171.124 Healthcare professionals should offer people with FH and their families written advice and information about patient support groups.
126.96.36.199 When lipid-modifying drug therapy is first considered for women and girls, the risks for future pregnancy and the fetus while taking lipid-modifying drug therapy should be discussed. This discussion should be revisited at least annually.
188.8.131.52 Healthcare professionals should give women and girls with FH specific information tailored to their needs and should offer a choice of effective contraceptive methods.
184.108.40.206 Combined oral contraceptives (COCs) are not generally contraindicated for women and girls being treated with lipid-modifying drug therapy. However, because there is a potential small increased risk of cardiovascular events with the use of COCs, healthcare professionals should consider other forms of contraception. Prescribers should refer to the summary of product characteristics of COCs and the relevant lipid-modifying drugs for their specific contraindications.
220.127.116.11 Healthcare professionals should be aware that, in general, there is no reason to advise against pregnancy or breastfeeding in women with FH.
18.104.22.168 Healthcare professionals should advise women with FH that lipid-modifying drug therapy should not be taken if they are planning to conceive or during pregnancy, because of the potential risk of fetal abnormality. Women should be advised that lipid-modifying drug therapy should be stopped 3 months before they attempt to conceive.
22.214.171.124 Women with FH who conceive while taking statins or other systemically absorbed lipid-modifying drug therapy should be advised to stop treatment immediately and they should be offered an urgent referral (see appendix D) to an obstetrician for a fetal assessment. Women should be fully informed about the nature and purpose of the assessment.
126.96.36.199 Women with FH who have conceived while taking statins or other systemically absorbed lipid-modifying drug therapy and have had a fetal assessment should be given time, opportunity and full information to consider their options (including the advantages and disadvantages) of continuing with their pregnancy.
188.8.131.52 Shared-care arrangements, to include expertise in cardiology and obstetrics, should be made for women with FH who are considering pregnancy or are pregnant. Such care should include an assessment of coronary heart disease risk, particularly to exclude aortic stenosis. This is essential for women with homozygous FH.
184.108.40.206 Serum cholesterol concentrations should not be measured routinely during pregnancy.
220.127.116.11 Women with FH who are pregnant should be advised on the potential risks and benefits of re-starting lipid-modifying drug therapy for the mother and breastfed infant. Resins are the only lipid-modifying drug therapy that should be considered during lactation.
18.104.22.168 All people with FH should be offered a regular structured review that is carried out at least annually.
22.214.171.124 A baseline electrocardiogram (ECG) should be considered for adults with FH.
126.96.36.199 Healthcare professionals should record the progress of cascade testing among the relatives of a person with FH as part of the structured review. This should include at least the first- and second- and, when possible, third-degree biological relatives. If there are still relatives who have not been tested, further action should be discussed.
188.8.131.52 Healthcare professionals should update the family pedigree of a person with FH and note any changes in the coronary heart disease status of their relatives as part of the structured review. This should include at least the first- and second- and, when possible, third-degree biological relatives.
184.108.40.206 Structured review should include assessment of any symptoms of coronary heart disease and smoking status, a fasting lipid profile, and discussion about concordance with medication, possible side effects of treatment the patient may be experiencing, and any changes in lifestyle or lipid-modifying drug therapy that may be required to achieve the recommended LDL-C concentration (see section 1.3).
220.127.116.11 Healthcare professionals should offer people with FH an urgent referral (see appendix D) to a specialist with expertise in cardiology for evaluation if they have symptoms or signs of possible coronary heart disease which are not immediately life-threatening. A low threshold for referral is recommended.
18.104.22.168 A person with FH with symptoms or signs of possible coronary heart disease which are immediately life-threatening (for example, acute coronary syndrome) should be referred to hospital as an emergency in line with advice for the general population.
22.214.171.124 Healthcare professionals should consider offering people with FH a referral for evaluation of coronary heart disease if they have a family history of coronary heart disease in early adulthood, or two or more other cardiovascular risk factors (for example, they are male, they smoke, or they have hypertension or diabetes).
126.96.36.199 Upon diagnosis, healthcare professionals should offer all adults and children/young people with homozygous FH a referral for an evaluation of coronary heart disease.
188.8.131.52 In asymptomatic children and young people with heterozygous FH, evaluation of coronary heart disease is unlikely to detect clinically significant disease and referral should not be routinely offered.
 This recommendation has been adapted from 'Ezetimibe for treating primary (heterozygous-familial and non-familial) hypercholesterolaemia' (NICE technology appraisal guidance 385).
 'The clinical effectiveness and cost effectiveness of bupropion (Zyban) and Nicotine Replacement Therapy for smoking cessation' (NICE technology appraisal guidance 39).