PCSK9 inhibitors

PCSK9 inhibitors (sometimes also shown as PCSK9i) are a new type of medicine for lowering cholesterol in the blood.

These medications are known as monoclonal antibodies, which means they are a type of laboratory-made protein that can bind to certain targets in the body. In this case they work by inhibiting a protein called PCSK9, which is made in the liver.

Research has shown that people with high levels of this protein tend to have high cholesterol throughout their lives and develop heart disease early, but people with low levels tend to have low cholesterol and a lower risk of heart disease. This discovery led to the development of PCSK9 inhibitors to lower cholesterol.

There are currently two PCSK9 inhibitors – Repatha (Evolocumab) and Praluent (Alirocumab) – and others are being developed at the moment.

In clinical studies, these medicines have lowered people’s cholesterol levels by more than half and are proven to lower the risk of cardiovascular disease (diseases of the heart and blood vessels, such as heart attacks and strokes). 

Who can take PCSK9 inhibitors?

PCSK9 inhibitors are usually prescribed by hospital specialists such as cardiologists and lipid clinics. They can be prescribed for people who are already taking statins and ezetimibe but their cholesterol level has not yet been brought down to target. They can also be an option for people who can’t take statins or ezetimibe.

If you have FH 

PCSK9 inhibitors have been approved for people who have FH (familial hypercholesterolaemia) and:

  • do not have cardiovascular disease and your LDL cholesterol is above 5mmol/L despite taking medications such as statins and ezetimibe 
  • have known cardiovascular disease and your LDL cholesterol is above 3.5mmol/L.

If you don’t have FH

They have also been approved for people who don’t have FH but have known diseases of the heart and blood vessels (cardiovascular disease). They can be prescribed for you if:

  • You are seen as ‘high risk’ and your LDL cholesterol is above 4mmol/L. ‘High risk’ means you have had a heart attack, have been in hospital with pain due to unstable angina, have had a procedure such as an angioplasty or stent, have heart disease, a previous stroke or peripheral arterial disease (PAD).
  • You are seen at ‘very high risk’ and your LDL cholesterol is above 3.5mmo/L. ‘Very high risk’ means you have had multiple episodes of the above illnesses or events or extensive cardiovascular disease.

How do PCSK9 inhibitors work?

Our liver cells have LDL receptors on the outside of them. These receptors attach to LDL cholesterol (sometimes called 'bad cholesterol') when it passes by in the blood. The receptor takes the cholesterol out of the blood and into the liver to be broken down. The more LDL receptors we have, the easier it is for us to keep our blood cholesterol low.

The PCSK9 protein breaks down the LDL receptors, meaning we have less of them and our blood cholesterol rises. PCSK9 inhibitors stop the protein from working so that we have more LDL receptors on our liver cells and less cholesterol in the blood.

How do you take PCSK9 inhibitors?

PCSK9 inhibitors are given by injection once every two to four weeks. Your doctor or nurse will show you how to give yourself the injections if possible, so you don’t need to go to hospital or your GP surgery to have them. Your doctor or nurse will support you with this.

After two to three months, you will have an appointment and a blood test to see how well the PCSK9 inhibitors are working. Depending on your results, your doctor will let you know how often you will need further blood tests.

Side effects of PCSK9 inhibitors

All medicines can have side effects, including PCSK9 inhibitors, but clinical studies have shown that they usually cause very few.

The most common side effects, which affect somewhere between 1 in 10 and 1 in 100 people, are:

  • flu-like symptoms such as cold, nausea, back pain and joint pain
  • soreness or itchiness where you give the injection
  • muscle pain.

If you do experience any side effects, contact your doctor.