Update of NICE Guidelines on management of Familial hypercholesterolemia

One in 500 people are born with a type of high cholesterol that runs in families, called familial hypercholesterolemia, or FH. Without treatment, people with FH have a high chance of developing heart disease earlier than most people. Starting with the right treatment as soon as possible is important, but many people don’t know they have the condition.NICE updates its guidelines for identifying and managing familial hypercholesterolemia (FH), a specific type of high cholesterol that runs in the family, in children, young people, and adults. The update of original guidelines published in 2008 aims to help identify people at increased risk of coronary heart disease as a result of having FH.

KEY RECOMMENDATIONS :

Management

Drug treatment

Adults

• The patients with FH should be informed that this treatment should be lifelong.


• High-intensity statin with the lowest acquisition cost should be offered as the initial treatment for all adults with FH and aim for at least a 50% reduction in LDL-C concentration from the baseline measurement


• 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)


• Ezetimibe monotherapy is recommended as an option for treating primary heterozygous-familial hypercholesterolaemia in adults in whom initial statin therapy is contraindicated


• Ezetimibe monotherapy is recommended as an option for treating primary heterozygous-familial hypercholesterolaemia in adults who cannot tolerate statin therapy


• 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 either after appropriate dose titration of initial statin therapy or because dose titration is limited by intolerance to the initial statin therapy and
  
  
  • a change from initial statin therapy to an alternative statin is being considered
  
  
  
  


• For the purposes of this guidance, appropriate control of cholesterol concentrations should be based on individualised risk assessment according to national guidance on managing cardiovascular disease in the relevant populations


• 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


• Prescribing of drug therapy for adults with homozygous FH should be undertaken within a specialist centre


• 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)


• 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)
  
  
  
  


• For recommendations on managing primary heterozygous familial hypercholesterolaemia in people whose LDL-C levels are not adequately controlled despite maximal tolerated lipid-lowering therapy,Alirocumab is recommended as an option for treating primary hypercholesterolaemia or mixed dyslipidaemia, only if:
  
  
  

  
  
  • Low‑density lipoprotein concentrations are persistently above the thresholds specified in table despite maximal tolerated lipid‑lowering therapy
  
  

  
  
  
  

  Low‑density lipoprotein cholesterol concentrations above which alirocumab is recommended

  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  

  	Without CVD	With CVD
  		High risk of CVD 1	Very high risk of CVD 2
  Primary non‑familial hypercholesterolaemia or mixed dyslipidaemia	Not recommended at any LDL‑C concentration	Recommended only if LDL‑C concentration is persistently above 4.0 mmol/l	Recommended only if LDL‑C concentration is persistently above 3.5 mmol/l
  Primary heterozygous‑familial hypercholesterolaemia	Recommended only if LDL‑C concentration is persistently above 5.0 mmol/l	Recommended only if LDL‑C concentration is persistently above 3.5 mmol/l
  1High risk of cardiovascular disease is defined as a history of any of the following: acute coronary syndrome (such as myocardial infarction or unstable angina requiring hospitalisation), coronary or other arterial revascularisation procedures, coronary heart disease, ischaemic stroke, peripheral arterial disease. 2Very high risk of cardiovascular disease is defined as recurrent cardiovascular events or cardiovascular events in more than 1 vascular bed (that is, polyvascular disease). Abbreviations: CVD, cardiovascular disease; LDL‑C, low‑density lipoprotein cholesterol.

  
  


• 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) or a fibrate to reduce their LDL-C concentration


• The decision to offer treatment with a bile acid sequestrant (resin) or a fibrate in addition to initial statin therapy should be taken by a specialist with expertise in FH


• Healthcare professionals should exercise caution when adding a fibrate to a statin because of the risk of muscle-related side effects (including rhabdomyolysis). Gemfibrozil and statins should not be used together

Children and young people

• All children and young people diagnosed with, or being investigated for, a diagnosis of FH should be referred l to a specialist with expertise in FH in children and young people .


• 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:
  
  
  
  • their age
  
  
  • the age of onset of coronary heart disease within the family, and
  
  
  • the presence of other cardiovascular risk factors, including their LDL-C concentration
  
  
  
  

Adults and children/young people

• 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


• 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)


• 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


• Routine monitoring of creatine kinase is not recommended in asymptomatic adults or children/young people with FH who are receiving treatment with a statin

Lifestyle interventions

• Healthcare professionals should regard lifestyle advice as a component of medical management, and not as a substitute for lipid-modifying drug therapy

Diet

• 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 fat
  
  
  
  


• Healthcare professionals should advise people with FH to eat at least five portions of fruit and vegetables a day


• Healthcare professionals should advise people with FH to consume at least two portions of fish a week (one of which should be oily fish).

Physical activity

• Healthcare professionals should advise people with FH to take at least 30 minutes of physical activity a day, of at least moderate intensity such as brisk walking, using stairs and cycling, at least 5 days a week


• 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

Weight management

• 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

Alcohol consumption

• 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.

Smoking advice

• 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.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

Information needs and support

Information and counselling on contraception for women and girls with FH

• 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.

Ongoing assessment and monitoring

Review

• All people with FH should be offered a regular structured review that is carried out at least annually.


• A baseline electrocardiogram (ECG) should be considered for adults with FH


• 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

Referral for evaluation of coronary heart disease

• Healthcare professionals should offer people with FH an urgent referral 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


• 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

For more details click on the link: www.nice.org.uk/guidance/CG71