Lifetime cumulative exposure to low-density lipoprotein cholesterol (LDL-C) is among the key modifiable risk factors for atherosclerotic cardiovascular disease (ASCVD). Absolute LDL-C levels and the duration of exposure have been repeatedly demonstrated in observational and experimental studies as the driving forces behind the atherosclerotic process. This knowledge is the foundation for an effort to develop long-acting potent LDL-C–lowering drugs to achieve sustained reductions in ASCVD risk.