Lipoprotein(a)-apheresis in the light of new drug developments
1Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Ziemssenstrasse 1, 80336 Muenchen, Germany.
Insights
Elevated lipoprotein(a) (Lp(a)) significantly increases cardiovascular disease risk. While lipoprotein apheresis is effective, new drug therapies are needed to specifically lower Lp(a) levels and reduce cardiovascular events.
Area of Science:
- Cardiology
- Lipidology
- Pharmacology
Background:
- Elevated lipoprotein(a) (Lp(a)) is a significant risk factor for early and severe cardiovascular disease (CVD).
- A desirable Lp(a) level of <50 mg/dl is now recommended for clinical decision-making.
- Existing cholesterol-lowering therapies, except for poorly tolerated niacin, do not effectively reduce Lp(a).
Purpose of the Study:
- To review current strategies for managing elevated Lp(a) and cardiovascular risk.
- To evaluate the efficacy and limitations of lipoprotein apheresis.
- To explore emerging pharmacological therapies targeting Lp(a).
Main Methods:
- Review of existing literature on Lp(a) management, including apheresis and pharmacological interventions.
- Analysis of retrospective and prospective data on the effectiveness of lipoprotein apheresis in reducing cardiovascular events.
- Examination of clinical trial data for novel lipid-modifying drugs and specific Lp(a)-lowering agents.
Main Results:
- Lipoprotein apheresis effectively reduces Lp(a) levels by over 60% and is associated with reduced cardiovascular events.
- Newer lipid-modifying drugs show varying degrees of Lp(a) reduction (e.g., Mipomersen ~25%, CETP-inhibitors ~50%, PCSK9-inhibitors ~30%).
- An apo(a) antisense oligonucleotide demonstrated significant, dose-dependent Lp(a) reduction in a Phase 1 trial.
Conclusions:
- Lipoprotein apheresis remains the standard of care for high-risk patients with severe CVD and elevated Lp(a), despite its cost and accessibility limitations.
- Emerging drug therapies, particularly those specifically targeting Lp(a) like antisense oligonucleotides, hold promise for future treatment.
- Further prospective randomized trials are necessary to confirm the cardiovascular benefits of new Lp(a)-lowering therapies.
Abstract:
Elevated levels of lipoprotein(a) (Lp(a)) contribute to the risk of early and severe cardiovascular disease (CVD). Recently <50 mg/dl was recommended as the desirable level for clinical use and decision making. All established medical therapies to lower cholesterol levels have no impact on lowering Lp(a) except niacin which is all too often poorly tolerated and not obtainable everywhere. Lipoprotein apheresis is an extracorporeal treatment to lower levels of Lp(a) significantly by > 60%. In some countries it is recommended in very high risk patients with early or progressive CVD. Retrospective data indicate that regular apheresis reduces cardiovascular events, which was substantiated by a recent prospective observational trial. Apheresis is very well tolerated with very few side effects, but it is expensive, time consuming, and offered by specialised centres only. To improve the overall treatment new drug therapies are required. Some of the recently approved lipid modifying drugs lower Lp(a) in addition to LDL-cholesterol: Mipomersen ∼ 25%, CETP-inhibitors ∼ 50%, PCSK9-inhibitors ∼ 30%. If the Lp(a) lowering effect contributes to the expected reduction of CVD events has to be shown in the future. The apo(a) antisense oligonucleotide is the only approach to specifically lower Lp(a). A phase 1 trial showed a decrease in a dose dependant manner (up to 88.8%) in healthy volunteers. Despite the lack of prospective randomised trials apheresis these days remains the standard of care in patients with elevated Lp(a) and severe CVD.
