Existing and emerging strategies to lower Lipoprotein(a)

Abundant evidence links elevated levels of lipoprotein(a) (Lp(a)) to higher cardiovascular risk, leaving clinicians with the challenge of what measures to take to mitigate Lp(a)-associated risk. Some therapies that may reduce cardiovascular risk, such as aspirin, statins, fibrates, and ezetimibe, have little effect on Lp(a) and in some cases may even increase its concentration. Other agents that reduce levels of Lp(a), such as niacin or cholesteryl ester transfer protein inhibitors, have neutral or only slightly favorable effects on cardiovascular outcomes. The only currently available therapeutic approaches that lower Lp(a) and reduce cardiovascular risk are PCSK9 inhibitors and lipoprotein apheresis. For PCSK9 inhibitors, the magnitude of clinical benefit is associated with the baseline level of Lp(a) and appears to be associated with the degree of Lp(a) reduction. Antisense oligonucleotides and small interfering RNA agents targeting apolipoprotein(a) have the potential to reduce circulating Lp(a) concentrations by more than 70%. The results of cardiovascular outcomes trials will determine whether such substantial reductions in Lp(a) are associated with meaningful clinical benefit.