Does Repatha (evolocumab) lower lipoprotein(a) (Lp(a))?

From the Guidelines

Repatha (evolocumab) lowers lipoprotein(a) (Lp(a)) by 27%, as demonstrated in the FOURIER trial 1. This reduction is significant and suggests that evolocumab can have a beneficial effect on Lp(a) levels, in addition to its well-established efficacy in reducing LDL cholesterol.

Key Points

• The FOURIER trial, a large-scale randomized controlled trial, found that evolocumab reduced Lp(a) levels by 27% 1.
• This reduction in Lp(a) levels is considered clinically meaningful, as elevated Lp(a) is an independent cardiovascular risk factor.
• Evolocumab's mechanism of action, which involves inhibiting PCSK9, may have a broader impact on lipid metabolism than previously thought, including effects on Lp(a) levels.

Clinical Implications

• For patients with elevated Lp(a) levels, evolocumab may be a useful therapeutic option to reduce cardiovascular risk.
• However, it is essential to note that the reduction in Lp(a) levels with evolocumab is modest, and other therapeutic approaches may be needed for patients with very high Lp(a) levels.
• Further research is necessary to fully understand the clinical implications of evolocumab's effects on Lp(a) levels and to determine the optimal treatment strategies for patients with elevated Lp(a).

Evidence Summary

• The FOURIER trial provides high-quality evidence for the efficacy of evolocumab in reducing Lp(a) levels 1.
• The trial's findings suggest that evolocumab can be a valuable addition to the treatment arsenal for patients with elevated Lp(a) levels and cardiovascular disease.

From the Research

Effect of Repatha (Evolocumab) on Lipoprotein(a) (Lp(a))

• Repatha (evolocumab) has been shown to lower lipoprotein(a) (Lp(a)) levels in several studies 2, 3, 4, 5.
• A study published in the Journal of cardiovascular development and disease found that a single injection of evolocumab resulted in a decrease of Lp(a) of 14% in healthy individuals with hyperlipoproteinemia(a) 3.
• Another study published in the Journal of clinical apheresis found that evolocumab reduced Lp(a) levels by 45.5% in patients with familial hypercholesterolemia and high cardiovascular risk, which was significantly higher than the reduction achieved with LDL-apheresis 4.
• A pooled analysis of phase 2 and phase 3 studies published in the Journal of the American Heart Association found that evolocumab substantially reduced median lipoprotein(a) levels by 22-38% at 12 weeks, with effects persisting over 5 years 5.

Comparison with Other Treatments

• Evolocumab has been compared to LDL-apheresis in patients with familial hypercholesterolemia and high cardiovascular risk, and was found to be more effective in reducing Lp(a) levels 4.
• The combination of evolocumab and LDL-apheresis may be a therapeutic alternative to achieve lower Lp(a) levels in patients with very high cardiovascular risk 4.

Consistency of Effects

• The effects of evolocumab on Lp(a) levels have been consistent across various patient populations, including those with hypercholesterolemia, mixed dyslipidemia, statin intolerance, heterozygous familial hypercholesterolemia, and type 2 diabetes mellitus 5.
• The lipid-lowering effects of evolocumab, including the reduction of Lp(a) levels, have been maintained over 5 years in some studies 5.