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Lipoprotein(a): the revenant.

Baris Gencer1, Florian Kronenberg2, Erik S Stroes3

  • 1Cardiology Division, Geneva University Hospitals, Switzerland.

European Heart Journal
|March 23, 2017
PubMed
Summary

Lipoprotein(a) [Lp(a)] is now recognized as a causal factor in cardiovascular disease. Promising therapies, including apheresis, PCSK9 inhibitors, and antisense therapy, are being developed to lower Lp(a) levels.

Keywords:
Cardiovascular preventionLipidsPharmacological therapiesRisk factors

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Area of Science:

  • Cardiovascular Medicine
  • Lipidology
  • Pharmacology

Background:

  • Lipoprotein(a) [Lp(a)] was historically underestimated but is now recognized for its causal role in cardiovascular disease and aortic valve stenosis.
  • Genetic studies, particularly Mendelian randomization, have provided strong evidence for the atherogenic nature of elevated Lp(a).
  • Previous therapeutic approaches primarily targeted LDL cholesterol, with Lp(a)-lowering effects being secondary.

Purpose of the Study:

  • To review current and emerging therapeutic strategies for lowering lipoprotein(a) [Lp(a)].
  • To highlight the significance of Lp(a) as a therapeutic target in cardiovascular disease.
  • To discuss the potential of novel drug developments in managing cardiovascular risk associated with high Lp(a).

Main Methods:

  • Review of genetic studies, including Mendelian randomization, establishing the causal link between Lp(a) and cardiovascular disease.
  • Analysis of existing and investigational therapies targeting Lp(a) reduction.
  • Evaluation of clinical trial data for lipid apheresis, PCSK9 inhibitors, and antisense therapy.

Main Results:

  • Lipid apheresis effectively reduces Lp(a) concentrations and cardiovascular endpoints.
  • PCSK9 inhibitors lower LDL cholesterol and decrease Lp(a) by approximately 30%.
  • Antisense therapy targeting apolipoprotein(a) has demonstrated up to 90% Lp(a) reduction in early trials without affecting other lipids.

Conclusions:

  • Multiple promising therapeutic avenues exist to specifically lower Lp(a) and mitigate cardiovascular risk.
  • Antisense therapy shows significant potential for substantial Lp(a) reduction, pending Phase 3 outcome data.
  • The development of targeted Lp(a)-lowering therapies represents a major advancement in cardiovascular disease prevention.