Lowering LDL-Cholesterol and CV Benefits: Is There a Limit to How Low LDL-C Needs to be for Optimal Health Benefits?

Atherosclerotic cardiovascular disease (ASCVD) is the number one cause of morbidity and mortality worldwide. Low-density lipoprotein cholesterol (LDL-C) has been implicated as one of the major risk factors causing ASCVD based on multiple hierarchical levels of evidence. The advent of powerful LDL-C lowering therapies, such as the proprotein convertase subtilisin/kexin type 9 inhibitor, have raised the question of how low to target LDL-C and whether there are any adverse safety events associated with a very low LDL-C level. The present review summarizes the available evidence and concludes that even a very low LDL-C is associated with cardiovascular benefit, although the magnitude of benefit depends on baseline ASCVD risk and the absolute change in LDL-C with pharmacologic therapy. The safety data in patients treated for very low LDL-C is reassuring, although it is inconsistent and requires longer term follow-up.