What are PCSK9 Inhibitors and how do they work?
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:
- In adults with heart 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-C)-lowering therapies, in adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia (HeFH), to reduce LDL-C.
- In addition to other LDL-C-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-C-lowering therapies in pediatric patients aged 8 years and older with HeFH to reduce LDL-C.
Repatha is approved to be used:
- In adults with heart disease to reduce the risk of heart attack, stroke, and coronary revascularization (a procedure to restore blood flow in blocked arteries or veins).
- In adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia (HeFH), to reduce LDL. Used alone or with other LDL-lowering therapies, in addition to diet.
- In children aged 10 years and older with HeFH, to reduce LDL. Used in addition to diet and other LDL-C-lowering therapies.
- In adults and children aged 10 years and older with homozygous familial hypercholesterolemia (HoFH), to reduce LDL. Used in addition to other LDL-C-lowering therapies.
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 cholesterol (LDL-C).
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:
- atorvastatin (Lipitor)
- simvastatin (Zocor)
- rosuvastatin (Crestor)
- pravastatin
- fluvastatin
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.
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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.
- Praluent and Repatha may be used alone (with diet) OR as an add-on drug (with drugs like a statin) plus diet. These 2 agents can reduce the risk of heart attack, stroke, and other heart complications in adults with heart disease.
- Leqvio is only indicated by the FDA to be used in combination with a statin and diet at this time, and it is not known if it will lower the risk of cardiovascular morbidity and mortality.
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 receptors.
- Leqvio blocks the PCSK9 protein by interfering with the translation of PCSK9 messenger RNA. It inhibits the intracellular synthesis of PCSK9.
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
- Leqvio prescribing information. 7/2023. Novartis. Accessed March 12, 2024 at https://www.novartis.com/us-en/sites/novartis_us/files/leqvio.pdf
- Praluent Prescribing Information. 3/2024. Regeneron, Sanofi. Accessed March 12, 2024 at https://www.regeneron.com/downloads/praluent_pi.pdf
- Repatha prescribing information. Revised 9/2021. Amgen Inc. Thousand Oaks, CA. Accessed March 12, 2024 at https://www.pi.amgen.com/-/media/Project/Amgen/Repository/pi-amgen-com/repatha/repatha_pi_hcp_english.pdf
- FDA Approves Amgen's Repatha (evolocumab) to Prevent Heart Attack and Stroke. Drugs.com. Dec. 1, 2017. Accessed March 12, 2024 https://www.drugs.com/newdrugs/fda-approves-amgen-s-repatha-evolocumab-prevent-heart-attack-stroke-4655.html
- FDA Approves Leqvio (inclisiran), First-in-Class siRNA to Reduce Low-Density Lipoprotein Cholesterol (LDL-C). Dec. 22, 2021. Drugs.com. Accessed March 12, 2024 at https://www.drugs.com/newdrugs/fda-approves-leqvio-inclisiran-first-class-sirna-reduce-low-density-lipoprotein-cholesterol-ldl-c-5760.html
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
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