Evolocumab and Alirocumab for treating dyslipidaemia

There are two new guidelines from NICE on the use of Evolocumab and Alirocumab for treating primary hypercholesterolaemia (both familial and non-familial) and mixed dyslipidaemia.

What are these drugs?

  • Both Evolocumab and Alirocumab are monoclonal antibodies that inhibit an enzyme that down-regulates LDL receptors. This therefore increases the number of LDL receptors and so increases LDL uptake and reduces plasma LDL levels.
  • They are given by subcutaneous injection.
  • In most patients, they will be used in triple therapy with statins and ezetimibe. They can be used with just statins, or just with ezetimibe or other lipid lowering drugs. They can also be used alone.

When can they be used?

Evolocumab comes in 2 doses, but only the 140mg every 2 weeks dose is recommended (the higher dose is not cost-effective enough). Alirocumab comes in 75 or 150mg doses and both can be used.

They can be used when LDL levels are persistently above those specified below, despite maximum tolerated lipid-lowering therapy.

1) Primary non-familial hypercholesterolaemia or Mixed dyslipidaemia:

  • Without CVD - Not recommended with LDL at any level
  • With high risk CVD - LDL > 4 mmol/L
  • With very high risk CVD - LDL > 3.5 mmol/L

2) Primary heterozygous familial hypercholesterolaemia:

  • Without CVD - LDL > 5 mmol/L
  • With high risk CVD - LDL > 3.5 mmol/L
  • With very high risk CVD - LDL > 3.5 mmol/L

High risk CVD is classified as a history of: ACS (eg MI or unstable angina requiring hospitalisation), coronary or other arterial revascularisation, chronic heart disease, ischaemic stroke, peripheral arterial disease.

Very high risk CVD is classified as a history of: recurrent cardiovascular events, or polyvascular disease (eg events in more than one area).

What else is worth knowing?

  • They are more effective at lowering LDL than statins or ezetimibe.
  • There is no current evidence that they bring a reduction in CV events as the trials were not powered to look at this. However there is good evidence that LDL lowering through other drugs does reduce CV events, so there is a presumption that these drugs will too.
  • In the Evolocumab guideline it is noted that there is a theoretical risk that its effects may be reduced over time due to production of neutralising antibodies. However there is no evidence that this happens in the trials. It is not mentioned in the Alirocumab guideline that I could see.
  • It is also noted in the Evolocumab guideline that the trials did not include some patients with diabetes. However, the experts (rather optimistically I thought), did not feel that this was an issue as ‘in clinical practice, people with diabetes would have their blood glucose levels controlled before being treated for primary hypercholesterolaemia’.

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