From the Guidelines
The treatment approach for individuals with elevated Apolipoprotein(a) (Apo(a)) levels should focus on aggressive management of overall cardiovascular risk factors, with first-line therapy including high-intensity statins and lifestyle modifications. The primary goal is to reduce the risk of cardiovascular disease, as elevated Apo(a) levels are a known risk factor for cardiovascular disease and calcific aortic valve disease 1. Key components of the treatment approach include:
- High-intensity statins such as atorvastatin 40-80mg daily or rosuvastatin 20-40mg daily to lower LDL cholesterol
- Lifestyle modifications, including a heart-healthy diet low in saturated fats, regular physical activity, smoking cessation, and weight management
- Consideration of specialized treatments like PCSK9 inhibitors (evolocumab or alirocumab) for patients with very high Lp(a) levels and established cardiovascular disease
- Lipoprotein apheresis in extreme cases for those with recurrent cardiovascular events despite maximal therapy It is essential to note that novel therapies specifically targeting Lp(a), such as antisense oligonucleotides, are in development but not yet widely available 1. The comprehensive approach is necessary because Apo(a) is genetically determined and not significantly reduced by conventional lipid-lowering therapies, making overall cardiovascular risk reduction the primary goal while specific Lp(a)-lowering treatments continue to evolve. In clinical practice, it is crucial to prioritize the management of overall cardiovascular risk factors, as the current evidence suggests that this approach can help reduce the risk of cardiovascular events in individuals with elevated Apo(a) levels 1.
From the Research
Apo(a) Screening and Treatment Approach
- The treatment approach for individuals with elevated Apolipoprotein(a) (Apo(a)) levels is complex, and current guidelines recommend measuring Lp(a) for risk assessments 2.
- Lipoprotein apheresis is the only approved treatment for elevated Lp(a), but it is time-intensive for the patient and only modestly effective 2.
- Pharmacological approaches to reduce Lp(a) levels and its associated risks are of significant interest, but currently available lipid-lowering therapies have limited effectiveness in reducing Lp(a) levels 2, 3.
Current Therapies for Elevated Lp(a) Levels
- Statins are first-line agents to reduce LDL cholesterol levels, but they modestly increase Lp(a) levels and have not been shown to change Lp(a)-mediated ASCVD risk 2, 4.
- Proprotein convertase subtilisin/kexin-type 9 (PCSK9) inhibitors effectively reduce plasma Lp(a) levels, which is believed to decrease residual cardiovascular risk 3, 5.
- Niacin also lowers Lp(a) levels, but its effectiveness in mitigating Lp(a)-mediated ASCVD risk remains unclear, and its side effects have limited its utilization 2, 6.
Emerging Therapies for Elevated Lp(a) Levels
- Investigational compounds targeting Lp(a), including small interfering RNA (siRNA) agents (olpasiran, SLN360) and an antisense oligonucleotide (pelacarsen), are in various stages of development 2, 6.
- These compounds block the translation of messenger RNA (mRNA) into apo(a), a key structural component of Lp(a), thereby substantially reducing Lp(a) synthesis in the liver 2.
- Emerging nucleic acid-based therapies have potent Lp(a)-lowering effects and appear safe, but phase 3 trials will establish whether they improve cardiovascular outcomes 6.