PCSK9 Inhibitors Mechanism of Action and Landmark Trials

What is PCSK9?

Our liver makes a protein called proprotein convertase subtilisin/kexin type 9 (PCSK9). PCSK9 regulates how many LDL receptors you have. Studies have shown that if you have naturally high PCSK9, you are more likely to have high cholesterol.

PCSK9 inhibitors decrease LDLR degradation by PCSK9, and thereby improve LDL-C clearance and lower plasma LDL-C

Here are some landmark trials on PCSK9 inhibitors:

Landmark Trials on PCSK9 Inhibitors

1. *FOURIER Trial (2017)*: Evaluated the efficacy and safety of evolocumab (Repatha) in reducing cardiovascular events in patients with established cardiovascular disease. Results showed a 15% reduction in major cardiovascular events.

2. *ODYSSEY OUTCOMES Trial (2018)*: Assessed the efficacy and safety of alirocumab (Praluent) in reducing cardiovascular events in patients with acute coronary syndrome. Results showed a 15% reduction in major cardiovascular events.

3. *SPIRE-1 and SPIRE-2 Trials (2014)*: Evaluated the efficacy and safety of bococizumab (not approved) in reducing LDL-C levels in patients with hypercholesterolemia. Although the trials showed significant LDL-C reductions, the drug was not approved due to immunogenicity concerns.

4. *GAUSS-3 Trial (2014)*: Assessed the efficacy and safety of evolocumab in reducing LDL-C levels in patients with statin intolerance. Results showed significant LDL-C reductions and improved tolerability.

These trials have demonstrated the efficacy and safety of PCSK9 inhibitors in reducing LDL-C levels and cardiovascular events, and have helped establish their role in the management of hypercholesterolemia and cardiovascular disease.

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𝘼𝙣𝙩𝙞𝙘𝙤𝙖𝙜𝙪𝙡𝙖𝙩𝙞𝙤𝙣 𝘼𝙛𝙩𝙚𝙧 𝙎𝙩𝙧𝙤𝙠𝙚

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