Pharmacological methods to lower lipoprotein(a) levels

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.