There are two that are FDA approved: alirocumab (Praluent) and evolocumab (Repatha).
What is the biological basis of PCSK9 inhibitors?
LDL-R (for receptor) is found on the surface of hepatocytes. These receptors pick out LDL-c from the circulation, lowering the LDL level in the bloodstream. That’s a good thing!
PCSK9 is a protein that balances out the effect of LDL-R by binding to LDL-R and getting it degraded, thereby not allowing LDL-c to get reabsorbed. This means LDL levels may go up. (See this illustration and explanation) The PCSK9 inhibitors (mAbs) bind to PCSK9, which allows LDL-R to keep doing it’s job, and keep LDL-c levels low.
Are PCSK9 inhibitors effective?
Yes. They are especially effective at reducing LDL levels when combined with statins. This review goes into exhaustive detail about trial data. However, no one knows for sure if they, like statins, reduce mortality from cardiovascular disease.
What caveats do I need to know about these drugs?
- Injected, not in pill form. This may be a barrier for some patients who either can’t (or won’t) inject themselves
- These drugs are expensive! A year’s supply of evolocucamb is estimated to cost about $14,500. It’s unclear how much of that may be covered by insurance
- The most common side effects are nasopharyngitis, congestion, and myalgia, but there are concerns about allergic reactions (it’s a monoclonal antibody) and cognitive impairment (subjective, but was reported in the phase III trials).
- Patients with severe kidney and liver disease were excluded from studies, so if, for example, you have a patient with cirrhosis who wants to start one of these medications, talk with their hepatologist
- Long-term studies on these drugs are lacking; there is a Cochrane review that reports that overall, follow up times for PCSK9 inhibitor studies have been short (26 months at the longest) and there have been few reported events.