How Do PCSK9 Lipid Lowering Therapies Work for FH

Expanded PBS access to PCSK9 inhibitors may offer new options for people with FH.

For people living with familial hypercholesterolaemia (FH), lowering LDL-cholesterol (“bad cholesterol”) is essential to reduce the risk of heart attack and stroke. While diet and lifestyle changes are important, most people with FH need medication to reach safe cholesterol levels.

In recent years, medications called PCSK9 inhibitors have become an increasingly important part of cholesterol treatment, and access to these therapies on the PBS has broadened. The importance of PCSK9 was first recognised through studies of people who naturally have very low levels of this protein. These individuals have lifelong low LDL-cholesterol levels and a markedly reduced risk of cardiovascular disease, providing the basis for developing PCSK9-targeting therapies.

PCSK9 is a protein that reduces the liver’s ability to remove LDL-cholesterol from the blood. PCSK9 inhibitors work by reducing the effect of this protein, allowing the liver to clear more LDL-cholesterol and significantly lower cholesterol levels. There are currently two PCSK9 inhibitors available in Australia. One – Repatha® (evolocumab) – is given as a self-injection every two weeks. Another – Leqvio® (inclisiran) – works by reducing PCSK9 production in the liver and is given twice yearly.

PCSK9 inhibitors do not replace cholesterol tablets. They are ideally used alongside statins and ezetimibe, which work in different ways. Using these treatments together can help people with FH achieve larger reductions in LDL-cholesterol. PBS access to PCSK9 inhibitors now reflects this evolving role. In general terms, treatment may be considered for those with FH whose LDL-cholesterol remains above 5.0 mmol/L despite treatment, or people at high cardiovascular risk with a previous heart attack or stroke whose LDL-cholesterol remains above 1.8 mmol/L.

Key points:

PCSK9 inhibitors are based on natural genetic insights into lifelong low cholesterol.
Access on the PBS has broadened for people with FH and those with high cardiovascular risk.
There are now different dosing options, including twice-yearly treatment.
PCSK9 inhibitors are usually added to statins and ezetimibe in order to obtain optimal LDL reduction.
Your doctor can help decide whether this treatment is right for you.