What the suboptimal rollout of LDL-C therapy should teach the field before Lp(a)-lowering drugs reach the clinic, Sarraju and Nissen argue (Am J Prev Cardiol 2025)

Reducing plasma low-density lipoprotein cholesterol (LDL-C) levels is a critical component of managing atherosclerotic cardiovascular disease (ASCVD) risk. However, LDL-C goal attainment and the use of LDL-C lowering therapies, which include cost-effective statins and multiple non-statin therapies, have remained suboptimal. In this setting, ASCVD remains the leading cause of morbidity and mortality in the US and globally. Due to persistent ASCVD risk despite LDL-C lowering, there has been strong interest in approaches to identify factors contributing to residual ASCVD risk beyond LDL-C levels. In particular, lipoprotein (a) [Lp (a)] has emerged as a leading target for multiple ongoing development programs of novel, potent pharmacologic agents that decrease Lp (a) levels, with ongoing clinical trials evaluating their effects on ASCVD events. This review outlines key lessons learned from the suboptimal implementation of LDL-C therapies that may be relevant to better implementation of future residual ASCVD risk reduction strategies, particularly for Lp (a) therapies that may be proven in clinical trials and approved by regulatory authorities in the future.