II. Mechanism
- PCSK9 Inhibitors are monoclonal antibodies
- Inhibit PCSK9 (Proprotein Convertase subtilisin/kexin type 9)
- Antibodies bind PCSK9 and prevent their binding to LDL receptors
- Results in lowering of LDL Cholesterol
- PCSK9 binds to LDL receptors on hepatocytes
- Promotes LDL receptor degradation on binding
- Prevents LDL Cholesterol clearance from circulation
- Raises serum LDL Cholesterol levels
III. Indications
- Severe Familial Hypercholesterolemia (e.g. LDL Cholesterol >190 mg/dl)
IV. Background
- Available in U.S. as of 2015
V. Medications
- PCSK9 Inhibitor
- See PCSK9 Small Interfering RNA
VI. Efficacy
- See disadvantages below
- Lower LDL Cholesterol up to 60%
- Repatha added to Statin for 2 years prevents one more CV event per 74 treated ($2,000,000 per CV event prevented)
VII. Disadvantages
- Very expensive agents (>$10,000 per year in 2022)
- New, with only short-term data
- Unknown longterm safety
- Unknown mortality reduction (contrast with proven Statin efficacy)
VIII. References
- (2015) Presc Lett 22(9): 50-1
- (2022) Non-StatinLipid Lowering Agents, Presc Lett, #380202
- (2022) Med Lett Drug Ther 64(1659): 145-52
- Robinson (2015) N Engl J Med 372(16):1489-99 +PMID:25773378 [PubMed]
- Stroes (2014) J Am Coll Cardiol 63(23):2541-8 [PubMed]