Beyond lipid lowering: Pleiotropic effects of statins in inflammation, coagulation, and cell proliferationmechanisms and clinical implications

Abstract

Statins are widely used lipid-lowering agents that substantially reduce cardiovascular morbidity and mortality by inhibiting 3-hydroxy-3-methylglutaryl coenzyme A reductase. Beyond their cholesterol-lowering properties, increasing evidence indicates that statins exert several pleiotropic effects that are independent of lipid reduction. These effects include anti-inflammatory, antithrombotic, and antiproliferative actions mediated primarily via the inhibition of the mevalonate pathway and downstream signaling molecules such as Rho, Rac, and Ras. Experimental and clinical studies have suggested potential benefits of statins in various noncardiovascular conditions, including autoimmune diseases, venous thromboembolism, sepsis-associated coagulopathy, and certain malignancies. In addition, pharmacoepidemiologic studies have provided insights into the real-world effects and safety profile of statins, including the risk of new-onset diabetes mellitus. This review summarizes the current evidence on the molecular mechanisms and clinical implications of statin pleiotropic effects beyond its lipid-lowering properties. However, much of the evidence supporting noncardiovascular benefits is derived from observational studies. Therefore, further randomized controlled trials are required to clarify causality, optimal patient selection, and therapeutic strategies for statin repurposing.