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Lipoprotein(a): cardiovascular risk and emerging therapies

Masashi Fujino¹, Stephen J Nicholls^1,2

¹Victorian Heart Institute, Monash University, Melbourne, Australia.

Expert Review of Cardiovascular Therapy

|April 3, 2023

Abstract

Introduction:

There is abundant evidence that elevated lipoprotein(a) [LP(a)] associates with cardiovascular risk. Most lipid modifying therapies don't reduce Lp(a), but new technologies are emerging that act upstream, such as antisense oligonucleotides (ASO) and small interfering RNAs (siRNAs) that inhibit the translation of mRNA for proteins specifically involved in lipid metabolism.

Areas Covered:

Despite the benefit of therapies for the prevention of atherosclerotic cardiovascular disease (ASCVD), Lp(a) is one of the 'residual risks,' established by observational and Mendelian randomization studies. Although current established lipid modifying therapies targeting low-density-lipoprotein cholesterol, such as statins and ezetimibe, do not lower Lp(a), ASOs and siRNAs demonstrated significant reduction of Lp(a) by -98 to -101% in recent clinical trials. However, we still don't know if specifically lowering Lp(a) reduced cardiovascular events, how much Lp(a) lowering is required to produce clinical benefit, and whether diabetes and inflammation have any impact. This review summarizes Lp(a), the knowns and unknowns about Lp(a), and focus emerging treatments.

Expert Opinion:

New Lp(a) lowering therapies have the potential to contribute to the personalized prevention of ASCVD.

Keywords:

ASO Lipoprotein(a)cardiovascular prevention inhibitors of apolipoprotein(a) synthesis siRNA

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