Beyond LDL-C reduction: molecular pleiotropy and emerging therapeutic roles of statins

Statins rank among the most prevalent pharmacological treatments for the prevention and management of atherosclerotic cardiovascular disease, chiefly by inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase and consequently reducing low-density lipoprotein cholesterol (LDL-C) levels. In addition to their recognized lipid-lowering properties, experimental, translational, and clinical research has uncovered various possible pleiotropic effects. These cholesterol-independent effects relate to the modulation of the mevalonate pathway and subsequent signaling molecules, which may affect endothelial function, nitric oxide availability, oxidative stress, inflammatory responses, atherosclerotic plaque stability, and thrombotic mechanisms. Nonetheless, the degree to which these processes yield clinically significant advantages apart from LDL-C lowering is still ambiguous. The clinical pharmacology of statins is examined, encompassing their pharmacokinetic and pharmacodynamic characteristics, molecular mechanisms of action, and novel therapeutic applications. Particular attention is directed at the molecular foundation and clinical relevance of statin pleiotropy in neurological conditions, metabolic disorders, inflammatory and autoimmune diseases, infectious illnesses, and cancer. The advantages and drawbacks of these prospective indications are rigorously assessed utilizing data from preclinical investigations, observational studies, randomized controlled trials, and meta-analyses. The evaluation additionally discusses safety factors, clinically significant drug–drug interactions, and the influence of pharmacogenomics in formulating individualized treatment approaches. Overall, statins have well-established cardiovascular benefits, whereas the clinical significance of their proposed pleiotropic effects and potential applications beyond cardiovascular disease varies across indications and remains incompletely established. Further high-quality, indication-specific clinical trials are needed to determine whether these effects provide additional therapeutic benefits and to define their appropriate clinical roles.