PCSK9 Inhibitors

Summary

PCSK9 Inhibitors are medications that include the drug names evolocumab and alirocumab. As lipid-lowering drugs, the PCSK9 inhibitors are used clinically to treat patients with hyperlipidemia.

These drugs work by inactivating the degradation of LDL receptors. This then increases the removal of LDL from blood.

In laboratory testing, patients taking PCSK9 inhibitors typically experience a very large lowering of LDL levels. This lowering of LDL is the primary effect of these drugs, although patients may also experience a lowering of triglyceride levels, and a raising of HDL levels. 

Side effects of taking PCSK9 Inhibitors include myopathy. Neurocognitive deficits.have also been associated with these drugs, which can present as dementia or delirium.

Key Points

• PCSK9 Inhibitors
  • Drug Names
    • Alirocumab
    • Evolocumab
  • Clinical Use
    • Lipid Lowering Drug
      • Used to lower levels of lipids like cholesterol and triglycerides in the bloodstream
  • Mechanisms
    • Inactivates LDL-Receptor Degradation
      • PCSK9 normally binds to and promotes degradation of LDL-Receptors within hepatocytes
      • PCSK9 Inhibitors are antibodies that bind to PCSK9, preventing them from binding to LDL-Receptors and causing their breakdown
    • Increases removal of LDL from bloodstream
      • LDL-Receptors normally function to remove LDL from the circulation
      • By increasing LDL-Receptor expression on hepatocytes, the liver removes more LDL from the bloodstream
  • Labs
    • ↓↓↓ LDL
      • Reduces LDL in a dose-dependent manner by as much as 70 percent from pre-treatment levels in patients
    • ↑ HDL
    • ↓ Triglycerides
  • Side Effects
    • Neurocognitive Defects
      • Declines in working memory, spatial memory, and reaction time
      • Delirium
      • Dementia
    • Myopathy (myalgia)
      • This is controversial; case reports have been documented but use of PCSK9 inhibitors has not been demonstrated to cause myopathy