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Novel Therapies for Lipoprotein(a): Update in Cardiovascular Risk Estimation and Treatment

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Abstract

Purpose of Review

Lipoprotein(a) is an important causal risk factor for cardiovascular disease but currently no available medication effectively reduces lipoprotein(a). This review discusses recent findings regarding lipoprotein(a) as a causal risk factor and therapeutic target in cardiovascular disease, it reviews current clinical recommendations, and summarizes new lipoprotein(a) lowering drugs.

Recent Findings

Epidemiological and genetic studies have established lipoprotein(a) as a causal risk factor for cardiovascular disease and mortality. Guidelines worldwide now recommend lipoprotein(a) to be measured once in a lifetime, to offer patients with high lipoprotein(a) lifestyle advise and initiate other cardiovascular medications. Clinical trials including antisense oligonucleotides, small interfering RNAs, and an oral lipoprotein(a) inhibitor have shown great effect on lowering lipoprotein(a) with reductions up to 106%, without any major adverse effects.

Summary

Recent clinical phase 1 and 2 trials show encouraging results and ongoing phase 3 trials will hopefully result in the introduction of specific lipoprotein(a) lowering drugs to lower the risk of cardiovascular disease.

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Data Availability

No datasets were generated or analysed during the current study.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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Acknowledgements

We thank the staff and participants from the Copenhagen General Population Study for their valuable contributions.

Funding

Novo Nordisk Foundation (grant NNF21OC0071977) (ABW), Aase and Ejnar Danielsen Fund (BGN), Independent Research Fund Denmark (BGN). The funders had no role in the design of the study or in the collection, analysis, interpretation of data, writing the manuscript, or the decision to submit the article for publication.

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Authors and Affiliations

  1. Department of Clinical Biochemistry, Copenhagen University Hospital - Herlev and Gentofte, Herlev, Denmark

    Anders Berg Wulff & Børge G. Nordestgaard

  2. The Copenhagen General Population Study, Copenhagen University Hospital - Herlev and Gentofte, Herlev, Denmark

    Anders Berg Wulff, Børge G. Nordestgaard & Anne Langsted

  3. Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

    Anders Berg Wulff, Børge G. Nordestgaard & Anne Langsted

  4. The Copenhagen City Heart Study, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Frederiksberg, Denmark

    Børge G. Nordestgaard

  5. Department of Clinical Biochemistry, Copenhagen University Hospital - Rigshospitalet, Blegdamsvej 9, DK-2100, Copenhagen Ø, Denmark

    Anne Langsted

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  1. Anders Berg Wulff
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Contributions

ABW performed the literature search and wrote the first draft of the manuscript. ABW, BGN, and AL revised the manuscript for critical scientific content. All authors read and approved the final manuscript.

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Correspondence to Anne Langsted.

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Conflict of Interest

BGN reports consultancies and talks sponsored by AstraZeneca, Sanofi, Regeneron, Akcea, Ionis, Amgen, Kowa, Denka, Amarin, Novartis, Novo Nordisk, Esperion, Abbott, Silence Therapeutics, Mankind, Ultragenyx, and Lilly. AL reports a talk sponsored by Amarin. ABW does not have any financial competing interests.

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All reported studies/experiments with human or animal subjects performed by the authors have been previously published and complied with all applicable ethical standards (including the Helsinki declaration and its amendments, institutional/national research committee standards, and international/national/institutional guidelines).

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Wulff, A.B., Nordestgaard, B.G. & Langsted, A. Novel Therapies for Lipoprotein(a): Update in Cardiovascular Risk Estimation and Treatment. Curr Atheroscler Rep 26, 111–118 (2024). https://doi.org/10.1007/s11883-024-01192-9

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