Anti-PCSK9 treatment: Is ultra-low LDL always good?

Anti-pcsk9 (proprotein convertase subtilisin kexin 9) monoclonal antibodies (Mab) are novel, potent lipid-lowering drugs. They demonstrated to improve the lipid profile in high cardiovascular risk patients. Anti-pcsk9 Mab inhibit the targeted LDL-receptor degradation induced by pcsk9 protein and are able to reduce LDL cholesterol (LDL-C) levels on top of conventional lipid-lowering therapy.Though these drugs proved to be very safe in the short term, little is known about the possible long term effects, due to the short period of their marketing. The genetic low-cholesterol syndromes (LCS) represent the natural models of the lipid-lowering anti-PCSK9 therapy, and a valuable opportunity to predict the long term effects of these drugs. By looking at the clinical features of such models we could be able to foresee possible drug-induced side effects. In the present review the correspondences and discordances between the side effects of anti-pcsk9 therapy and the corresponding LCS models will be examined in the attempt to forecast possible long term consequences of these novel lipid lowering agents