Lipoprotein(a) and Atherosclerotic Cardiovascular Disease, the Impact of Available Lipid-Lowering Medications on Lipoprotein(a): An Update on New Therapies

Objective To review evidence of existing and new pharmacological therapies for lowering lipoprotein(a) (Lp[a]) concentrations and their impact on clinically relevant outcomes. Methods We searched for literature pertaining to Lp(a) and pharmacological treatments in PubMed. We reviewed articles published between 1963 and 2020. Results We found that statins significantly increased Lp(a) concentrations. Therapies that demonstrated varying degrees of Lp(a) reduction included ezetimibe, niacin, proprotein convertase subtilisin/kexin type 9 inhibitors, lipoprotein apheresis, fibrates, aspirin, hormone replacement therapy, antisense oligonucleotide therapy, and small interfering RNA therapy. There was limited data from large observational studies and post hoc analyses showing the potential benefits of these therapies in improving cardiovascular outcomes. Conclusion There are multiple lipid-lowering agents currently being used to treat hyperlipidemia that also have a Lp(a)-lowering effect. Two RNA therapies specifically targeted to lower Lp(a) are being investigated in phase 3 clinical trials and, thus far, have shown promising results. However, evidence is lacking to determine the clinical relevance of reducing Lp(a). At present, there is a need for large-scale, randomized, controlled trials to evaluate cardiovascular outcomes associated with lowering Lp(a).