PCSK9 Inhibitors

Introduction
Illustrated mechanism of action
Examples of Medication Brand Names (with Images)
Indication
Side Effects
Precautions & Contraindications
Monographs
Reference

Introduction (Drug history )

PCSK9 inhibitors are a breakthrough cholesterol-lowering treatment developed after the discovery of the PCSK9 gene in 2003. Genetic studies showed that mutations in this gene affect cholesterol levels and heart disease risk. The first PCSK9 inhibitors, approved in 2015, significantly reduce LDL cholesterol and help patients who cannot reach targets with statins or who are statin intolerant. Administered by injection, these drugs have improved cardiovascular outcomes and represent an important advance in managing high cholesterol and preventing heart disease.

Mechanism of Action

PCSK9 inhibitors are a new class of cholesterol-lowering drugs that effectively reduce low-density lipoprotein cholesterol (LDL-C) levels in the blood. PCSK9 is a protein produced by the liver that binds to LDL receptors on liver cells, leading to their degradation and reducing the liver’s ability to remove LDL cholesterol from the bloodstream. By inhibiting PCSK9, these drugs prevent the destruction of LDL receptors, allowing more receptors to recycle back to the liver cell surface. This increases the clearance of LDL cholesterol from the blood, resulting in a significant reduction in LDL-C levels. PCSK9 inhibitors, such as alirocumab and evolocumab, are especially useful for patients who do not reach cholesterol goals with statins or who are statin-intolerant, and they have been shown to reduce cardiovascular risk effectively.

Medication brand name

praluent (alirocumab)

Leqvio (inclisiran)

Repatha (evolocumab)

Indication

PCSK9 inhibitors are primarily indicated for patients with established or high risk of cardiovascular disease and familial hypercholesterolemia who need additional lowering of LDL cholesterol despite maximally tolerated statin and/or ezetimibe therapy. They are used as adjuncts to diet and statin therapy to reduce LDL-C levels, particularly in those with clinical atherosclerotic cardiovascular disease (ASCVD) or familial hypercholesterolemia. These drugs can reduce LDL cholesterol by up to 60-70% and lower the risk of cardiovascular events such as heart attacks. They are also considered for patients who are statin-intolerant or have inadequate LDL-C lowering on conventional therapy

Side Effect

PCSK9 inhibitors like alirocumab and evolocumab are generally well tolerated. The most common side effects are:

- Injection site reactions (pain, redness, swelling)

- Flu-like symptoms (nasopharyngitis, upper respiratory infections, fatigue, feeling cold)

- Muscle-related symptoms (myalgia, back pain, arthralgia, muscle spasms)

- Headache and dizziness

- Occasionally, urinary tract infections

- Rarely, severe allergic reactions such as anaphylaxis

These side effects are usually mild to moderate and often resolve over time. Muscle symptoms are less frequent than with statins. Overall, PCSK9 inhibitors have a favorable safety profile in both clinical trials and real-world use

Dizziness

Muscle -related symptoms

Flu-like symptoms

Precautions & Contraindications

Contraindications of PCSK9 Inhibitors

- Known hypersensitivity or allergy to the drug (e.g., evolocumab, alirocumab) or any of its ingredients.

- History of severe allergic reactions such as angioedema to these medications.

- Latex allergy: Some formulations (e.g., certain needle covers) contain latex and should not be used in patients with latex sensitivity.

- Not recommended during pregnancy or breastfeeding.

Precautions:

- Injection Site Care: Avoid injecting into painful, thickened, bruised, red, or swollen skin; rotate injection sites to prevent irritation.

- Storage: Store refrigerated; do not freeze or heat. Can be kept at room temperature for a short period (usually up to 30 minutes) before use.

- Hypersensitivity Monitoring: Monitor for allergic reactions and advise patients to report unusual symptoms promptly.

- Latex Sensitivity:Use latex-free devices if the patient is sensitive to latex.

- LDL Monitoring: Regular LDL cholesterol checks are necessary to assess effectiveness and adjust therapy.

- Adjunct Therapy:PCSK9 inhibitors should be used in addition to, not as a replacement for, lifestyle changes and other cholesterol-lowering medications.

- Long-term Safety: Generally well tolerated, but rare neurocognitive or vitamin level changes have been reported; ongoing monitoring is advised.

- Pediatric Use: Not recommended in children unless specifically prescribed and closely monitored by a healthcare provider.

In summary, PCSK9 inhibitors are generally safe but require careful screening for allergies (including latex), monitoring for hypersensitivity, and ongoing assessment of cholesterol levels.

Monograph

Emailing DOC-20250323-WA0050..pdf

Emailing DOC-20250322-WA0002..pdf

Drug monograph-1.pdf

Reference

https://australianprescriber.tg.org.au/articles/pcsk9-inhibitors-mechanisms-of-action.html

https://journals.sagepub.com/doi/10.1177/10742484221100107

https://heartcare.sydney/pcsk9-inhibitors/

https://www.ncbi.nlm.nih.gov/books/NBK448100/

https://my.clevelandclinic.org/health/drugs/22550-pcsk9-inhibitors

https://www.webmd.com/cholesterol-management/pcsk9-inhibitors-treatment

https://pmc.ncbi.nlm.nih.gov/articles/PMC5079795/

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