Latest developments in the treatment of lipoprotein (a)

Lipoprotein (a) [Lp(a)] is an independent risk factor for cardiovascular disease. The aim of this review is to provide an overview of treatment options for Lp(a) lowering. Recent studies confirmed that lifestyle intervention and statins do not affect Lp(a) levels, whereas Lp(a) is lowered by oestrogens, niacin, and lipoprotein apheresis. Cholesterol ester transfer protein inhibitors and proprotein convertase subtilisin/kexin type 9 antibodies, currently studied in phase 3 trials, also lower Lp(a) concentrations by 30-50%. However, all of these compounds have modifying effects on multiple lipoprotein classes. An antisense oligonucleotide directed to apolipoprotein (a) has recently been developed to specifically lower circulating Lp(a) levels. This compound lowers Lp(a) mRNA up to 90%, and Lp(a) levels up to 82% in human volunteers independent of Lp(a) levels at baseline. Multiple agents, including the next generation RNA-based antisense therapeutics have Lp(a) lowering properties. However, it remains to be established whether lowering Lp(a) reduces cardiovascular disease events with specific Lp(a) lowering therapies.