How Low Can You Go? New Evidence Supports No Lower Bound to Low-Density Lipoprotein Cholesterol Level in Secondary Prevention

Reducing low density lipoprotein cholesterol (LDL-C) has been a cornerstone of atherosclerotic cardiovascular disease (ASCVD) risk reduction for over three decades. 1Guidelines from the US and Europe have delineated algorithms for LDL-C targeting, generally advocating for progressively lower values over time, tracking with the development of new therapies and evolving trial data. 2, 3However, along with the ability to achieve substantially lower LDL-C values has emerged a critical question-what are the benefits and safety of very low (10-40 mg/dL) LDL-C?Since their FDA approval in the late 1980's, statins have been the primary LDL-C reducing therapy in clinical practice.A central tenet that has emerged from over 20 statin randomized trials evaluated in a Cholesterol Treatment Trialists (CTT) meta-analysis is that for every 39 mg/dL (1mmol/L) LDL-C reduction with statins there is a 21% relative risk reduction in major adverse cardiovascular events (MACE). 4Early statin clinical trials largely applied low and moderate-intensity statins, with the first two trials achieving LDL-C values of 122 mg/dL and 98 mg/dL, respectively. 5,6 ccordingly, the US National Cholesterol Education Program Adult Treatment Panel (NCEP-ATP) revised recommendations for LDL-C goals from <130 mg/dL in secondary prevention in ATP I published in 1998 to <100 mg/dL in ATP II published in 1993.