Evolocumab and alirocumab are recommended by NICE as options for treating primary hypercholesterolaemia or mixed dyslipidaemia in patients with persistently raised LDL-C concentrations despite maximal tolerated lipid-lowering therapy.
The two antibodies, which belong to the class of injectable lipid-lowering drugs known as PCSK9 inhibitors, are recommended for NHS use at the following LDL-C thresholds:
|Without CVD||With CVD|
|High risk of CVD||Very high risk of CVD|
|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|
The drugs must be provided with the discount agreed in the patient access schemes, and evolocumab is only approved for NHS use at a dose of 140mg every 2 weeks.
High 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, chronic heart disease, ischaemic stroke, peripheral arterial disease.
Very high risk of cardiovascular disease is defined as recurrent cardiovascular events or cardiovascular events in more than 1 vascular bed (that is, polyvascular disease).
Evolocumab and alirocumab target the PCSK9 (proprotein convertase subtilisin kexin type 9) enzyme, preventing PCSK9-mediated degradation of LDL receptors on the surface of liver cells. This leads to an increase in the number of receptors available to clear LDL, thereby decreasing levels of LDL-C.