Does Repatha Lower HDL Cholesterol?
No, Repatha (evolocumab) does not lower HDL cholesterol—it primarily reduces LDL cholesterol by 50-65% while improving other lipid parameters including lipoprotein(a), but HDL levels are not adversely affected by this PCSK9 inhibitor. 1
Mechanism and Primary Effects
Evolocumab is a fully human monoclonal antibody that targets PCSK9, preventing the degradation of LDL receptors and thereby dramatically increasing LDL cholesterol clearance from the bloodstream. 2 The drug's mechanism specifically upregulates LDL receptor recycling without interfering with HDL metabolism or production. 1
Lipid Profile Changes with Evolocumab
The primary lipid effects of evolocumab include:
- LDL cholesterol reduction of 50-65% when added to statin therapy, with many patients achieving levels below 25 mg/dL 1
- Lipoprotein(a) reduction up to 25%, which provides additional cardiovascular benefit 1
- Reductions in total cholesterol, non-HDL cholesterol, apolipoprotein B, and triglycerides 2, 3
- No adverse effect on HDL cholesterol levels—the drug does not lower HDL 1
Clinical Context
The guideline evidence specifically discusses evolocumab's effects on "other lipid parameters" beyond LDL cholesterol, mentioning improvements in apolipoprotein A1 (which is associated with HDL) and other beneficial changes. 3 Importantly, when comparing different lipid-lowering agents, the guidelines note that fenofibrate increases HDL cholesterol by approximately 2.4%, contrasting this with PCSK9 inhibitors like evolocumab that focus on LDL reduction without negatively impacting HDL. 1
Key Clinical Takeaway
Evolocumab's cardiovascular benefit derives from its profound LDL cholesterol lowering (achieving median levels of 30 mg/dL in the FOURIER trial), not from HDL modification. 4 The drug reduced cardiovascular death, myocardial infarction, and stroke by 20% through LDL reduction alone, demonstrating that HDL changes are not necessary for clinical benefit in this context. 4
Common Pitfall to Avoid
Do not confuse evolocumab with fibrates or niacin, which do raise HDL cholesterol. PCSK9 inhibitors work through an entirely different mechanism focused on LDL receptor biology and do not share the HDL-raising properties of those older agents. 1