PCSK9 inhibitors, management of uncontrolled familial hypercholesterolaemia

This guideline only refers to treatment of adult patients with heterozygous familial hypercholesterolaemia (HeFH) and

• LDL-C ≥5.0mmol/L, for primary prevention of cardiovascular events.
• LDL-C ≥3.5mmol/L, for secondary prevention of cardiovascular events.

Treatment will be managed by specialists within NHS GGC lipid clinics

• All patients with suspected HeFH should be referred to a Lipid Clinic for confirmation of the diagnosis, assessment and management.
• All known HeFH patients with uncontrolled hyperlipidaemia despite maximum treatment with a statin ± ezetimibe should be referred to a Lipid Clinic for consideration of a PCSK9 inhibitor.

N.B. Please refer to the Coronary Heart Disease and Stroke, Primary and Secondary Prevention Guideline for the management of hypercholesterolaemia in high-risk cardiovascular disease patients without FH.

Alirocumab and evolocumab are inhibitors of proprotein convertase subtilisin kexin type 9 (PCSK9).

The criteria for consideration of PCSK9 inhibitors in HeFH patients, with and without cardiovascular disease, is outlined in the attached flowcharts. These flowcharts are based on European Society of Cardiology guidance (1), amended to reflect SMC advice. (2,3)

Alirocumab

The usual starting dose is 75 mg every 2 weeks given by subcutaneous injection. This may be increased to 150mg every 2 weeks if target LDL-C is not achieved.

If a greater than 60% reduction in LDL-C is required, the higher dose of 150 mg every 2 weeks may be used as a starting dose. (4)

Evolocumab

The dose accepted for use in NHS Scotland is 140mg every 2 weeks given by subcutaneous injection (excludes 420mg once monthly). (5)

LDL-C plasma concentrations should be rechecked 4 weeks after commencement of therapy and after any dose changes.

The manufacturers of alirocumab (Sanofi) and evolocumab (Amgen) will arrange the provision of initial patient education, training on self-administration and ongoing support services for patients commenced on this medicine. This does not replace routine follow-up by prescribers.

Prescriptions for alirocumab and evolocumab will be issued by the patient’s GP on receipt of a written request from a Consultant Biochemist.

All routine follow-up of these patients, including any specific monitoring requirements for alirocumab and evolocumab, will be undertaken by the Lipid Clinic initiating treatment. The patient’s GP will continue to provide routine clinical care.

Please refer to the alirocumab and evolocumab summary of product characteristics for full prescribing advice.

This is a new medicine and therefore reporting suspected adverse reactions is important to allow quick identification of new safety issues. Healthcare professionals are asked to report any suspected adverse reactions via Yellow Card Scheme at: www.mhra.gov.uk/yellowcard

1. https://academic.oup.com/eurheartj/article-
   abstract/doi/10.1093/eurheartj/ehw480/2418178/European-Society-of-Cardiology-European?redirectedFrom=fulltext Accessed 17th January 2017
2. https://www.scottishmedicines.org.uk/SMC_Advice/Advice/1147_16_alirocumab_Praluent/alirocumab_Praluent Accessed 17th January 2017
3. https://www.scottishmedicines.org.uk/medicines-advice/?active-tab=0&node-id=6990&keywords=1148%2F16&filter-3561=&filter-3567=&filter-3803=&from=&to=&total-results-0=2&total-results-1=0 Accessed 28th February 2017
   
4. http://www.medicines.org.uk/emc/medicine/30956 Accessed 17th January 2017
5. http://www.medicines.org.uk/emc/medicine/30628 Accessed 28th February 2017