What are PCSK9 Inhibitors and how do they work?
The PCSK9 inhibitors are used for the treatment of 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. They are given by subcutaneous (under the skin) injection
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.
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 close to 4 decades.
Statin medicines (also called HMG CoA reductase inhibitors) are easily identified because they all end in “statin.” They are available in brand name and generic options. Generic options are very affordable for most patients.
Some common statin examples include:
- atorvastatin (Lipitor)
- fluvastatin (Lescol XL)
- lovastatin (Altoprev)
- pitavastatin (Livalo, Zypitamag)
- pravastatin
- rosuvastatin (Crestor)
- simvastatin (Zocor).
FDA Approved Uses for PCSK9 Inhibitors
Praluent
Praleunt is approved by the FDA to be used:
- In adults with heart (cardiovscular) disease to reduce the risk of heart attack, stroke, and certain types of chest pain (unstable angina) requiring hospitalization.
- With diet, alone or in combination with other low-density lipoprotein cholesterol (LDL)-lowering therapies, in adults with high blood cholesterol (primary hyperlipidemia), including inherited heterozygous familial hypercholesterolemia (HeFH), to reduce LDL, or bad cholesterol.
- In addition to other LDL lowering therapies in adult patients with homozygous familial hypercholesterolemia (HoFH) to reduce LDL-C. HoFH is a rare genetic and possibly deadly condition characterized by very high levels of LDL-C and an elevated risk for early heart disease.
- In addition to diet and other LDL lowering therapies in children aged 8 years and older with inherited heterozygous familial hypercholesterolemia (HeFH) to reduce LDL.
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Repatha
Repatha is approved to be used:
- To reduce the risk of major adverse cardiovascular (CV) events, such as death from cardiovascular disease, heart attack, stroke, certain types of chest pain conditions (unstable angina) requiring hospitalization, or certain types of heart surgery, in adults at increased risk for these events.
Repatha is also used along with diet and exercise to reduce low-density lipoprotein (LDL) or bad cholesterol in:
- Adults with high blood cholesterol levels called hypercholesterolemia.
- Adults and children aged 10 years and older with a type of high cholesterol called heterozygous familial hypercholesterolemia (HeFH).
- Adults and children aged 10 years and older with a type of high cholesterol called homozygous familial hypercholesterolemia (HoFH).
It is not known if Repatha is safe and effective in children with HeFH or HoFH who are younger than 10 years of age or in children with other types of hypercholesterolemia.
Leqvio
Leqvio is approved to be used:
- In addition to diet and statin therapy (another type of cholesterol-lowering medicine) for the treatment of adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia (HeFH), to reduce low-density lipoprotein ("bad") cholesterol (LDL-C).
- It can be used first-line as monotherapy (by itself) or given with other cholesterol medications, including statins.
Leqvio is used in adults with high blood cholesterol levels (called primary hyperlipidemia), including heterozygous familial hypercholesterolemia (HeFH), to reduce low-density lipoprotein (LDL-C) levels alongside dietary changes. It can be used first-line as monotherapy (by itself) or given with other cholesterol medications, including statins. Leqvio is administered by subcutaneous (under the skin) injection, twice a year.
How do the PCSK9 inhibitors work?
PCSK9 Mechanism of Action
Although all three drugs inhibit a protein called PCSK9 (proprotein convertase subtilisin kexin 9), they work by different mechanisms.
Repatha and Praluent are monoclonal antibodies that bind to PCSK9 in the liver and prevent it from binding to LDL ("bad choleserol") sites (called receptors).
Leqvio blocks the PCSK9 protein by interfering with the instructions of PCSK9 messenger RNA (mRNA). It inhibits the intracellular synthesis of PCSK9. This prevents breakdown of receptors in the liver that remove LDL cholesterol from blood. This allows more receptors to be available and increases LDL-C removal from the bloodstream. Leqvio belongs to the drug class called small interfering RNAs (siRNA).
It's important to target 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, stroke and heart-related death.
Ultimately, PCSK9 inhibitors 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. 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
- Leqvio prescribing information. 7/2025. Novartis. Accessed Aug 27, 2025 at https://www.novartis.com/us-en/sites/novartis_us/files/leqvio.pdf
- Praluent Prescribing Information. 3/2024. Regeneron, Sanofi. Accessed Aug 27, 2025 at https://www.regeneron.com/downloads/praluent_pi.pdf
- Repatha prescribing information. Revised 8/2025. Amgen Inc. Thousand Oaks, CA. Accessed Aug 27, 2025 at https://www.pi.amgen.com/-/media/Project/Amgen/Repository/pi-amgen-com/Repatha/Repatha-Full-Prescribing-Information-Interstitial.pdf
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.
Continue reading
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
See also:
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