From the Guidelines
Therapies that target elevated lipoprotein(a) (Lp(a)) levels to reduce cardiovascular risk are primarily focused on aggressive control of other cardiovascular risk factors, as there are no approved therapies specifically targeting Lp(a) levels. The most recent and highest quality study 1 suggests that the primary management strategy for patients with high Lp(a) should focus on aggressive control of other cardiovascular risk factors. Some therapies that have shown promise in reducing Lp(a) levels include:
- Niacin, which can lower Lp(a) by 20-30% 1
- PCSK9 inhibitors (evolocumab and alirocumab), which can modestly reduce Lp(a) by 20-30% 1
- Lipoprotein apheresis, a procedure similar to dialysis that physically removes Lp(a) from blood, available in some countries for patients with extremely high levels and progressive cardiovascular disease despite optimal management of other risk factors
- Emerging therapies such as antisense oligonucleotides like pelacarsen, which can reduce Lp(a) levels by up to 80% in clinical trials, and small interfering RNA (siRNA) therapies that target Lp(a) production in the liver 1. However, these novel approaches are still in clinical development and not yet available for routine clinical use. It is essential to prioritize the management of other cardiovascular risk factors, such as LDL cholesterol, hypertension, smoking, diabetes, and obesity, to reduce the risk of cardiovascular disease in patients with elevated Lp(a) levels. In particular, the 2024 recommendations on the optimal use of lipid-lowering therapy in established atherosclerotic cardiovascular disease and following acute coronary syndromes suggest that upfront lipid-lowering combination therapy should be considered to improve access and adherence to lipid-lowering therapy in patients at very high risk of cardiovascular disease 1. Overall, while there are no approved therapies specifically targeting Lp(a) levels, a comprehensive approach to managing cardiovascular risk factors and emerging therapies offer promise for reducing the risk of cardiovascular disease in patients with elevated Lp(a) levels.
From the Research
Therapies Targeting Elevated Lipoprotein(a) Levels
Therapies that target elevated lipoprotein(a) (Lp(a)) levels to reduce cardiovascular risk include:
- Pharmacological approaches such as niacin, which has been shown to lower Lp(a) levels by 20-38% 2, 3, 4
- Lipoprotein apheresis, which can reduce Lp(a) levels by approximately 20-30% 3, 5, 4
- Emerging therapies such as small interfering RNA (siRNA) agents (e.g. olpasiran, SLN360) and an antisense oligonucleotide (pelacarsen) that target apolipoprotein(a) and can substantially reduce Lp(a) synthesis in the liver 3, 5, 6
- Proprotein convertase subtilisin/kexin type 9 inhibitors, which can reduce Lp(a) levels by approximately 20-25% 3, 5
Current Limitations and Future Directions
Current therapies for elevated Lp(a) have limited effectiveness, and more research is needed to determine the clinical implications of reducing Lp(a) levels on cardiovascular risk 2, 3, 5, 4, 6
- There is a need for more clinical trials to examine the effects of Lp(a) reduction on cardiovascular risk in primary and secondary prevention populations 3, 4, 6
- Emerging therapies that specifically target Lp(a) may provide a more effective approach to reducing cardiovascular risk associated with elevated Lp(a) levels 3, 5, 6
Agents with Lp(a)-Lowering Effects
Agents that have been shown to lower Lp(a) levels include:
- Niacin, which can lower Lp(a) levels by 20-38% 2, 3, 4
- Aspirin, which has been shown to have a modest Lp(a)-lowering effect 4
- Estrogens, which can lower Lp(a) levels, but are not recommended for primary or secondary prevention of cardiovascular disease due to potential side effects 4
- Ezetimibe, which has been shown to lower Lp(a) levels in some studies, but requires further investigation 4