PCSK9 inhibitors (evolocumab / alirocumab / inclisiran)
Metabolic Health · Monoclonal antibody or siRNA
Tier S
What this is
Reserved historically for familial hypercholesterolemia, statin intolerance, or high-risk secondary prevention with inadequate LDL on maximal statin. Cost has dropped substantially but remains high. Inclisiran's 2x/year dosing is attractive for adherence. Lerodalcibep (Lerochol), a small monthly anti-PCSK9 recombinant protein, has reached approval as a newer option in the class.
Mechanism
Block PCSK9 (which degrades LDL receptors) — resulting LDL receptor recycling drives circulating LDL-C down 50-60% on top of statin; inclisiran is siRNA silencing PCSK9 mRNA, dosed every 6 months
Dose & route
Evolocumab 140 mg subQ q2wk or 420 mg monthly; alirocumab 75-150 mg subQ q2wk; inclisiran 284 mg subQ at 0, 3 mo, then every 6 mo
Citations
- https://pubmed.ncbi.nlm.nih.gov/28304224/
- https://pubmed.ncbi.nlm.nih.gov/30403574/
- https://pubmed.ncbi.nlm.nih.gov/32302303/
- https://doi.org/10.30682/ildia2601f
- https://pubmed.ncbi.nlm.nih.gov/41746457/
- https://pubmed.ncbi.nlm.nih.gov/41546841/
- https://pubmed.ncbi.nlm.nih.gov/41478627/
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