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Differential Effects of Lipid-lowering Drugs in Modulating Morphology of Cholesterol Particles
Published on: November 10, 2017
Emerging therapeutic agents to lower lipoprotein (a) levels
Brian Kolski1, Sotirios Tsimikas
1Division of Cardiology, Department of Medicine, University of California San Diego, La Jolla, California 92093-0682, USA.
Current Opinion in Lipidology
|October 9, 2012
Summary
Lipoprotein (a) [Lp(a)] is a key cause of cardiovascular disease. Emerging therapies, including antisense oligonucleotides and novel apo(a) inhibitors, show promise for lowering Lp(a) levels.
Area of Science:
- Cardiovascular Medicine
- Lipidology
- Pharmacology
Background:
- Lipoprotein (a) [Lp(a)] is increasingly recognized as a causal risk factor for cardiovascular disease (CVD).
- Genetic and epidemiological studies strongly support Lp(a)'s role in CVD pathogenesis.
- There is a significant unmet need for targeted therapies to reduce Lp(a).
Purpose of the Study:
- To review and summarize emerging therapeutic agents designed to lower Lp(a) levels.
- To discuss the potential of Lp(a) as a therapeutic target for CVD prevention.
- To highlight recent advancements in pharmacological and apheresis-based Lp(a) reduction.
Main Methods:
- Review of recent epidemiological and genetic studies on Lp(a) and CVD.
- Analysis of data on various emerging therapeutic strategies targeting Lp(a).
- Examination of agents including antisense oligonucleotides, monoclonal antibodies, and specific apo(a) inhibitors.
Main Results:
- Apheresis is currently the most effective method for Lp(a) reduction.
- Several drug classes, including antisense oligonucleotides to apoB and PCSK9 inhibitors, can lower Lp(a) alongside other lipoproteins.
- Novel apolipoprotein (a) [apo(a)] inhibitors demonstrate significant reductions in apo(a) mRNA and protein levels (up to 86%) without affecting other lipoproteins.
Conclusions:
- Lipoprotein (a) is the last major lipoprotein disorder lacking specific therapy.
- The robust evidence linking Lp(a) to CVD risk provides a strong rationale for developing novel Lp(a)-lowering agents.
- Future research should focus on testing whether reducing Lp(a) levels translates to decreased cardiovascular events.
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