PCSK9 Inhibitors

Summary for Physicians:

PCSK9i are a class of monoclonal antibodies that effectively lower LDL-C levels and are particularly useful for patients with high cardiovascular risk, including those with acute coronary syndrome (ACS) or familial hypercholesterolemia. Currently, 2 PCSK9i have been approved for clinical use.

Available PCSK9i:

1. Alirocumab (Praluent):
   1. Mechanism: Alirocumab is a fully human monoclonal antibody that targets PCSK9, preventing it from binding to LDL receptors on hepatocytes, which enhances the liver’s ability to clear LDL-C from the blood.
   2. Indications: It is approved for patients with heterozygous familial hypercholesterolemia or atherosclerotic cardiovascular disease (ASCVD) who need additional LDL-C level lowering, particularly in those not achieving sufficient reduction with statins or who are statin-intolerant.
   3. Dosing: Alirocumab is typically administered via subcutaneous injection every 2 weeks or every 4 weeks, depending on the patient's LDL-C level and response to treatment.
2. Evolocumab (Repatha):
   1. Mechanism: Similar to alirocumab, evolocumab is a monoclonal antibody that inhibits PCSK9, allowing for increased LDL receptor availability on liver cells and enhancing LDL-C clearance.
   2. Indications: Evolocumab is approved for patients with heterozygous familial hypercholesterolemia, ASCVD, and those requiring additional LDL-C level lowering beyond what statins alone can provide. It is also approved for primary hyperlipidemia and mixed dyslipidemia.
   3. Dosing: Evolocumab is typically administered via subcutaneous injection every 2 weeks or every 4 weeks, depending on the patient’s needs. In some cases, more frequent dosing may be necessary depending on LDL-C level goals.

Both medications have demonstrated significant efficacy in lowering LDL-C levels and improving cardiovascular outcomes in high-risk patients, particularly those who do not achieve adequate LDL-C level reduction with statin therapy alone. These PCSK9 inhibitors are generally well tolerated, with adverse effects being relatively rare and typically mild, such as injection site reactions.

In conclusion, alirocumab and evolocumab are the 2 PCSK9i currently available, offering valuable options for intensive LDL-C level lowering in high-risk patients, especially those with statin resistance or intolerance.