Although statins are the first-line treatment for individuals with high LDL cholesterol, familial hypercholesterolemia (FH), or high lipoprotein(a), also known as Lp(a), not all patients reach their LDL Safe Zone with statins.

In those cases, your healthcare provider may recommend the addition of a PCSK9 inhibitor.

There are currently two monoclonal antibodies available today in the United States to lower LDL cholesterol:

• Alirocumab (Praluent)
• Evolocumab (Repatha)

These drugs target proprotein convertase subtilisin kexin type 9 (PCSK9). This protein makes it harder for the body to remove LDL cholesterol from the blood.

PCSK9 inhibitors disable the PCSK9 protein, letting the liver perform its normal clearance process and remove LDL cholesterol from the bloodstream.

Alirocumab and evolocumab can help reduce LDL cholesterol by 50 to 60% and have been shown to reduce cardiovascular events. They are self-injections taken at home every 2 or 4 weeks.

There is currently one siRNA drug in the United States approved to lower LDL cholesterol:

• Inclisiran (Leqvio)

While inclisiran is also a PCSK9 inhibitor, it works differently from alirocumab and evolocumab. Inclisiran works inside the cells to prevent PCSK9 from being produced. With less PCSK9 around, cells can remove more LDL from the bloodstream.

Inclisiran was approved in late 2021 for individuals with heterozygous FH and for those with cardiovascular disease who have tried diet and maximally tolerated statins to lower their LDL.

This medication is given as an injection in the healthcare provider’s office. You’ll get your first shot, another one 3 months later, and then every 6 months after that – all in the healthcare provider’s office.

Inclisiran can help reduce LDL cholesterol by 50%.

Do not use PCSK9 inhibitors during pregnancy or while nursing, even though adverse pregnancy events have not been reported.