Vol 9, No 1 (2024)
Review article
Published online: 2024-02-14

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Pharmacological methods to lower lipoprotein(a) levels

Natalia Wierzbowska1, Joanna Olejnik-Wojciechowska1, Aleksandra Dąbrowska1, Karolina Żurawska1
Medical Research Journal 2024;9(1):96-102.

Abstract

Lipoprotein(a) exhibits proatherogenic properties, thus promoting the development of atherosclerotic
cardiovascular disease. Lp(a) levels are genetically determined and relatively constant at the turn of a
patient’s life. Even a single measurement could be an important screening test to distinguish a group of
patients with increased cardiovascular risk. Despite the lack of specific therapies, drugs with potential
effects on reducing Lp(a) levels include ezetimibe, PCSK-9 inhibitors, fibrates, inclisiran, olparisan, aspirin,
tocilizumab or mipomersen.

Although ezetimibe has shown a moderate effect on lowering Lp(a) in monotherapy, its combination with
statins does not provide a significant additional benefit in reducing Lp(a). PCSK-9 inhibitors contribute
to a significant reduction in cardiovascular risk in patients in whom maximum-dose statin therapy fails to
achieve lipoprotein targets. Patients with baseline higher Lp(a) levels receive greater benefit from PCSK9
inhibitor therapy. The use of aspirin to reduce Lp(a) levels could be most significant in rs3798220 carriers,
but the European Atherosclerosis Society does not support the advisability of such a drug. Studies involving
tocilizumab are promising, but data on non-RA groups are lacking. Mipomersen, on the other hand, has
shown significant lipoprotein(a)-lowering effects, but is only used to treat familial hypercholesterolemia
due to the risk of side effects.

The aim of this systematic review was to discuss lipoprotein(a)’s potential as an independent cardiovascular
risk factor and summarize pharmacological approaches available to lower its levels according to
currently available knowledge based on the main findings of randomized clinical studies, review studies
and meta-analyses.

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