PCSK9 inhibitors (evolocumab / alirocumab / inclisiran)
Metabolic Health · Monoclonal antibody or siRNA
Tier S
Bottom line
Read Off Label grades PCSK9 inhibitors (evolocumab / alirocumab / inclisiran) as S (8.7/10) based on strong evidence, very strong benefit magnitude, and a low-risk safety profile.
Reserved historically for familial hypercholesterolemia, statin intolerance, or high-risk secondary prevention with inadequate LDL on maximal statin.
Typical use: Evolocumab 140 mg subQ q2wk or 420 mg monthly; alirocumab 75-150 mg subQ q2wk; inclisiran 284 mg subQ at 0, 3 mo, then… — Rx.
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/
Links go to the source. If a link is dead or you want something re-checked, let me know.
Common questions
- Does PCSK9 inhibitors (evolocumab / alirocumab / inclisiran) work?
- Read Off Label rates the evidence for PCSK9 inhibitors (evolocumab / alirocumab / inclisiran) as Strong and the benefit magnitude as very strong, producing an overall grade of S (8.7/10). Reserved historically for familial hypercholesterolemia, statin intolerance, or high-risk secondary prevention with inadequate LDL on maximal statin.
- Is PCSK9 inhibitors (evolocumab / alirocumab / inclisiran) safe?
- PCSK9 inhibitors (evolocumab / alirocumab / inclisiran) has a low risk profile in published human data. Legal status: Rx (expensive at list; list prices now lower — ~$500-600/month after 2018 price cuts). This is not medical advice — see the disclaimer.
- What is the typical dose for PCSK9 inhibitors (evolocumab / alirocumab / inclisiran)?
- 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
- How does PCSK9 inhibitors (evolocumab / alirocumab / inclisiran) work?
- 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
This is an independent synthesis of published research by a non-clinician. Scores are opinions supported by citations, not prescriptions. See the full disclaimer and methodology for how this score was produced and what it does and doesn't mean.