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What are PCSK9 Inhibitors and how do they work?

Medically reviewed by Leigh Ann Anderson, PharmD. Last updated on March 12, 2024.

Official Answer by Drugs.com

The PCSK9 inhibitors are used for the treatment of high-risk patients with elevated cholesterol, especially when statins aren't adequate. They work by blocking PCSK9, leaving more receptors available to capture your "bad" cholesterol (LDL) for break down and removal from the blood.

PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9) inhibitors include the following medications:

About 1 in 5 patients on statins cannot lower their cholesterol enough, sometimes due to a serious genetic defect called familial hypercholesterolemia (FH). In addition, some patients stop their statin treatment due to side effects, like intolerable or dangerous muscle aches, muscle or liver damage from statins, elevated blood sugar, or other side effects.

FDA Approved Uses for PCSK9 Inhibitors

Praleunt is approved to be used:

Repatha is approved to be used:

Leqvio is approved to be used:

Can PCSK9 inhibitors be used with statins?

Yes, for many patients PCSK9 inhibitors may be used in addition to a statin to help lower high LDL cholesterol levels. Statins are also known as HMG-CoA reductase inhibitors and have been the cornerstone of treatment to help regulate cholesterol production for over 3 decades.

Available since the late 1980's, statins include well-known blockbusters like:

Statins work so well because they block an enzyme involved in the production of cholesterol in the liver and boost the number of low density lipoprotein (LDL) receptors to help clear the body of LDL (also known as "bad cholesterol"). But not all people can tolerate them and they may not lower cholesterol levels enough in some patients.

Related questions

How do the PCSK9 inhibitors work?

The PCSK9 inhibitors are a class of injectable drugs approved in 2015 that have been shown to dramatically lower LDL cholesterol levels -- by up to 60% in some reports -- when combined with a statin.

Mechanism of Action

Although all three drugs inhibit a protein called PCSK9 (proprotein convertase subtilisin kexin 9), they work by different mechanisms.

It's important to block PCSK9 because it inactivates the needed receptors on the liver cell surface that transport LDL into the liver for metabolism (break down). Lower levels of LDL is better for the heart, and can help to protect against heart disease, heart attacks and stroke.

Ultimately, these agents all have the same action, and that is to free LDL receptors on liver cells to allow LDL (bad cholesterol) to be removed from the blood. In short - by blocking PCSK9, more receptors are available to capture your "bad" cholesterol for break down and removal from the blood.

This is not all the information you need to know about Praluent, Repatha and Leqvio for safe and effective use and does not take the place of your doctor’s directions. Review the full product information and discuss this information and any questions you have with your doctor or other health care provider.

References

Read next

What is the difference between Leqvio and Repatha?

Leqvio and Repatha are both injectable medicines that are used for the treatment of high cholesterol, by specifically lowering low density lipoprotein (LDL) levels. Although they both inhibit PCSK9 they work by different mechanisms. Repatha is a monoclonal antibody that binds directly to PCSK9 in the liver preventing it from binding to LDL receptors. Leqvio blocks the PCSK9 protein by interfering with the translation of PCSK9 messenger RNA. Both have the same result – and that is freeing up LDL receptors on the surface of liver cells which allows LDL cholesterol to be removed from the blood.

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What is the best time of day to take Repatha?

You can inject Repatha at any time of the day, but usually people prefer injecting Repatha during daylight hours because it takes 30 to 45 minutes for it to warm up to room temperature, and you need to be able to easily see what you are doing while you are injecting it. Continue reading

How long can Repatha be kept unrefrigerated?

Repatha can be left unrefrigerated for up to 30 days at room temperature between 68°F to 77°F (20°C to 25°C) as long as it is kept in its original box and is not kept somewhere that gets hotter than 77°F (25°C), for example, a car glove box. This makes it easier to take your medicine with you when you’re on the go. Do not put Repatha back in the refrigerator once you have taken it out. Continue reading

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