Lipid Management Pathway

The AHSN NENC Cardiovascular Disease Prevention Programme has a focus on optimising the treatment of disordered lipids to give patients the best chance of avoiding cardiac events. This page has been created to provide information to healthcare professionals about the treatment options for disordered lipids, as outlined in the Lipid Management Pathway.

Until recently, statins has been the only treatment option to help lower patients’ cholesterol. However, newer drugs have now been approved for use including bempedoic acid, ezetimibe, Inclisiran and PCSK9i. These all have different uses within the pathway, but all give clinicians options for treating patients. Read more about these treatment options below, and for clinical use, please see the local NEELI (Northern England Evaluation and Lipid Intensification) guidelines.

To support the optimisation of lipid management, as part of our broader work to reduce the prevalence of Cardiovascular Disease (CVD), we have created a number of educational resources for healthcare professionals working in primary care which can be downloaded here.

What is a statin?

Statins are a class of lipid-lowering medications that reduce cholesterol levels in those who are at high risk of Cardiovascular Disease. They are the most common cholesterol-lowering drugs.

Large clinical research studies, involving many thousands of people, have shown that lowering bad cholesterol reduces your risk of heart disease – especially heart attacks.

Prescribing statins

There are several statins available in the UK. They all work in the same way, but have slightly different chemical structures. Statin choice and dose will be made depending on medical history and target cholesterol level. Most statins are taken at night, because more cholesterol is produced whilst people sleep, although some statins can be taken at any time of the day.

What is a Ezetimibe?

Ezetimibe is a “cholesterol absorption inhibitor” which works by partially blocking the absorption of cholesterol in the small intestine. This means less cholesterol enters your blood from food and bile so the liver has to take more cholesterol out of the blood to make more bile, which is needed for digestion.

The liver does this by increasing the number of low-density lipoprotein (LDL) receptors on your liver cells. These receptors catch LDL cholesterol as it passes by and removes it from the blood.

Prescribing Ezetimibe

Ezetimibe 10mg tablet taken once daily. It might be combined with a statin or taken on its own if a patient is unable to take statins.

Taking ezetimibe with a statin 

Ezetimibe works well in combination with a High Intensity Statin (HIST), such as Atorvastatin or Rosuvastatin, when statins alone are not reducing cholesterol levels down to target on their own, including for rare conditions such as homozygous FH and sitosterolaemia.

Taking ezetimibe only

Ezetimibe is licensed to be used on its own if a patient has primary hypercholesterolaemia, which includes heterozygous FH as well as other conditions, and is unable to take statins or they are not working.

Ezetimibe is not suitable during pregnancy or if someone is breastfeeding.

More information

Ezetimibe 10 mg tablets – Summary of Product Characteristics (SmPC) – (emc) (medicines.org.uk)

Overview | Ezetimibe for treating primary heterozygous-familial and non-familial hypercholesterolaemia | Guidance | NICE

What is a Bempedoic acid?

Bempedoic acid is a new treatment option for people with high cholesterol. It can be used when statins are not suitable, and ezetimibe is not working well enough on its own.

Like statins, bempedoic acid lowers cholesterol in the blood by reducing the production of cholesterol in the liver. Statins block an enzyme known as HMG-CoA reductase. Bempedoic acid works in a similar way, by slowing down a different enzyme in the cholesterol production pathway known as ATP citrate lyase – but only in the liver. This means there are more low-density lipoprotein (LDL) receptors in the liver, which helps to remove more LDL cholesterol from the blood.

Unlike statins, bempedoic acid only works in the liver so it is much less likely to cause side effects in the muscles – one of the main reasons some people do not take statins.

Prescribing Bempedoic Acid 

Bempedoic acid 180 mg once daily is indicated in adults with primary hypercholesterolaemia (heterozygous familial and non-familial) or mixed dyslipidaemia, as an adjunct to diet:

  • In combination with a statin or statin with other lipid-lowering therapies in patients unable to reach LDL-c goals with the maximum tolerated dose of a statin, or
  • Alone or in combination with other lipid-lowering therapies in patients who are statin intolerant, or for whom a statin is contraindicated.

More information

Overview | Bempedoic acid with ezetimibe for treating primary hypercholesterolaemia or mixed dyslipidaemia | Guidance | NICE

Nilemdo 180mg film-coated tablets – Summary of Product Characteristics (SmPC) – (emc) (medicines.org.uk)

What is Inclisiran?

Inclisiran is a first-in-class small interfering RNA therapy which received a licence from the European Commission in December 2020 following the results of a robust clinical development programme. The drug also gained NICE approval on 1 September 2021, recommending the drug for people with high cholesterol who have already had a previous cardiovascular event to reduce their LDL (low-density lipoproteins) cholesterol, which is a key risk factor for them having a subsequent event.

The drug removes harmful LDL cholesterol (LDL-c) from the blood and in three studies across over 3,700 patients is proven to reduce LDL-c by 50% by using RNA interference (RNAi) to boost the liver’s ability to remove it from the blood.

Prescribing Inclisiran 

Inclisiran is an LDL-c lowering therapy that, with two maintenance doses a year (following an initial dose and a follow-up dose at 3 months), delivers effective and sustained LDL-c reduction.

Inclisiran is indicated in adults for secondary prevention with primary hypercholesterolaemia or mixed dyslipidaemia as an adjunct to diet:

  • In combination with a statin or statin with other lipid lowering therapies, in patients unable to reach LDL-c goals with the maximum tolerated dose or a statin, or
  • Alone or in combination with other lipid-lowering therapies in patients who are statin intolerant, or for whom a statin is contraindicated.

Find out more about inclisiran and AHSN NENC’s role in rolling out this treatment here.

What is PCSK9i?

PCSK9i is a lipid lowering therapy (LLT) only prescribed to patients who have previously taken other forms of LLT (including high intensity statins and ezetimibe), however their cholesterol levels still remain above recommended levels.  It can also be administered to people who cannot tolerate statins.

Prescribing PCSK9i 

It is a self administered injection every 2 to 4 weeks and works differently to statins by reducing the amount of PCSK9 protein in the body, produced by the liver. In reducing the amount of PCSK9 protein, the inhibitors allow the body to remove cholesterol more effectively.

PCSK9i is much more expensive than a statin, however, cost savings are made against the number of heart attacks and strokes prevented.

As it is classed as a ‘red drug’, it can only be prescribed by a specialist in secondary care.

Find out more about AHSN NENC’s work as part of the Cardiovascular Disease Prevention programme here.