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# PCSK9 inhibitors

Injectable antibodies that stop PCSK9 from destroying LDL receptors. They lower LDL strongly on top of a statin and reduce cardiovascular events.

Updated 2026-11-01

## What they are

Monoclonal antibodies against PCSK9 (evolocumab, alirocumab), injected under the skin every few weeks. Used when a statin and ezetimibe are not enough or in familial hypercholesterolemia.

## Mechanism of action

PCSK9 is a protein secreted by the liver that binds the LDL receptor and sends it to the lysosome for destruction, instead of letting it recycle to the cell surface. The antibodies bind circulating PCSK9 and block its contact with the receptor, so more LDL receptors stay on hepatocytes and clear LDL from the blood. Statins raise PCSK9 production (through SREBP-2), which is one reason the two work well together.

Target: PCSK9 (proprotein convertase subtilisin/kexin type 9)

## Key points

- Add a large further LDL reduction to a maximally tolerated statin; they lowered heart attacks and strokes in outcome trials.
- Used in established atherosclerotic disease and in familial hypercholesterolemia.
- Ezetimibe is usually tried before a PCSK9 inhibitor, partly because of cost.
- Main adverse effects: injection-site reactions, nasopharyngitis and flu-like symptoms; no known drug interactions.
- Inclisiran is a different approach: a small interfering RNA that blocks PCSK9 production.

## Drugs in this class

- [**Evolocumab** A monoclonal antibody against PCSK9, injected under the skin. It keeps LDL receptors working, lowers LDL strongly and… PCSK9 (circulating protein)](https://durgical.com/en/pharmacology/evolocumab/)
- [**Alirocumab** A monoclonal antibody against PCSK9, injected every 2 or 4 weeks. It lowers LDL strongly and reduces cardiovascular… PCSK9 (circulating protein)](https://durgical.com/en/pharmacology/alirocumab/)

## Others in the class

- inclisiran (siRNA, not an antibody)

## Test yourself

Think of the answer, then tap the question to see it.

## What does PCSK9 normally do to the LDL receptor?

It binds the receptor and directs it to lysosomal degradation, so fewer receptors return to the cell surface.

## Why do statins and PCSK9 inhibitors complement each other?

Statins raise LDL receptors but also raise PCSK9; the antibody removes PCSK9, so the extra receptors survive.

## Which genetic variants first pointed to PCSK9 as a drug target?

Gain-of-function variants cause familial hypercholesterolemia, and loss-of-function variants give low LDL and less coronary disease.

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Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: [Evolocumab Injection: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a615043.html) (MedlinePlus (U.S. National Library of Medicine), 2025); Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th ed., ch. 37 (McGraw Hill, 2023); [PCSK9:EGF-A complex](https://www.rcsb.org/structure/3BPS) (RCSB Protein Data Bank, 2008).

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