Statins, LDL-C and Beyond: A Contemporary Review of Atherosclerotic Cardiovascular Risk Assessment and Management

Cardiovascular disease has been the leading cause of death in the United States since 1921 and remains a substantial cause of morbidity and mortality worldwide. Since the discovery of statins, significant improvements in outcomes have been achieved as these drugs have direct atherogenic lipid lowering properties as well as pleiotropic effects on atherosclerotic cardiovascular disease (ASCVD). In recent years, the American Heart Association and the American College of Cardiology published a 10-year ASCVD event risk calculator to standardized risk assessment and guide statin therapy. Over the last quarter century statins have become a cornerstone of primary and secondary ASCVD management. Our review explores the evolution of statin therapy from early groundbreaking trials to shaping current ASCVD guidelines. We investigate the mechanism of action of statins, their lesser-known side effects, and their impact on other lipid particles, coronary artery calcium scoring, and C-reactive protein levels. We examine how the current understanding of ASCVD risk factors and risk enhancers provides new insights to guide indeterminate treatment decisions in individuals with intermediate ASCVD risk profiles. Additionally, we explore the evolving landscape of ASCVD therapy as new targets like proprotein convertase subtilisin/kexin 9, Lp(a), and specific inflammatory markers have garnered interest. Our comprehensive review provides an in-depth discussion of statins and novel therapies in their clinical applications for healthcare providers in the management of ASCVD.