Effect of Repatha (Evolocumab) on Lipoprotein(a) Levels
Repatha (evolocumab) does reduce Lipoprotein(a) [Lp(a)] levels by approximately 25-27%, although this reduction is less pronounced than its effect on LDL cholesterol.
Mechanism and Evidence
- Evolocumab is a fully human monoclonal antibody that targets PCSK9 (proprotein convertase subtilisin/kexin type 9), increasing the availability of LDL receptors on liver cells 1
- The reduction in Lp(a) appears to be partly mediated through increased LDL receptor-mediated uptake, particularly when LDLR expression is increased and circulating LDL is low 2
- In a pooled analysis of 10 clinical trials involving 3,278 patients, evolocumab demonstrated:
- Median reduction in Lp(a) of 24.7% with biweekly dosing
- Median reduction of 21.7% with monthly dosing 2
- The FOURIER trial, which included 25,096 patients, showed evolocumab significantly reduced Lp(a) by a median of 26.9% at 48 weeks 3
Clinical Significance of Lp(a) Reduction
- Higher baseline Lp(a) levels are associated with increased cardiovascular risk independent of LDL-C levels 3
- In the FOURIER trial, patients with baseline Lp(a) above the median experienced:
Comparison to Other Lipid Parameters
- While evolocumab reduces Lp(a) by approximately 25%, it reduces LDL-C by 50-65% 1, 4
- The correlation between Lp(a) reduction and LDL-C reduction is moderate (r=0.37) 3
- Evolocumab also reduces:
- Total cholesterol
- Non-HDL cholesterol
- Apolipoprotein B
- Various lipoprotein particles including LDL-P, medium VLDL-P, small VLDL-P, and IDL-P 5
Clinical Implications
- For patients with elevated Lp(a) levels, evolocumab may provide additional cardiovascular risk reduction beyond LDL-C lowering
- Patients with higher baseline Lp(a) may derive greater benefit from evolocumab therapy 3
- Current guidelines recommend screening for Lp(a) in patients with:
- Premature cardiovascular disease
- Family history of premature CVD
- Familial hypercholesterolemia
- Recurrent or rapidly progressive vascular disease 6
Administration
- Repatha (evolocumab) is administered as:
- 140 mg subcutaneous injection every 2 weeks, or
- 420 mg subcutaneous injection once monthly 1
While evolocumab is not specifically approved for Lp(a) reduction, its ability to lower this independent cardiovascular risk factor provides an additional mechanism through which it may reduce cardiovascular events, particularly in patients with elevated baseline Lp(a) levels.