Current and Emerging Uses of Statins in Clinical Therapeutics: A Review

Abstract

Statins, a class of cholesterol-lowering medications that inhibit 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase, are commonly administered to treat atherosclerotic cardiovascular disease. Statin use may expand considerably given its potential for treating an array of cholesterol-independent diseases. However, the lack of conclusive evidence supporting these emerging therapeutic uses of statins brings to the fore a number of unanswered questions including uncertainties regarding patient-to-patient variability in response to statins, the most appropriate statin to be used for the desired effect, and the efficacy of statins in treating cholesterol-independent diseases. In this review, the adverse effects, costs, and drug-drug and drug-food interactions associated with statin use are presented. Furthermore, we discuss the pleiotropic effects associated with statins with regard to the onset and progression of autoimmune and inflammatory diseases, cancer, neurodegenerative disorders, strokes, bacterial infections, and human immunodeficiency virus. Understanding these issues will improve the prognosis of patients who are administered statins and potentially expand our ability to treat a wide variety of diseases.

Keywords: adverse effects; atherosclerotic cardiovascular disease; autoimmune and chronic inflammatory diseases; cancer; low-density lipoprotein cholesterol; statins.

Figure 1

Statin mechanism of action. (A) Statins attenuate HMG-CoA reductase enzymatic activity. (B) Intracellular cholesterol reduction. (C) SREBP cleavage and translocation. (D) SREBP promotes LDL-R gene expression. (E) LDL-R gene transcribed and translated. (F) LDL-R density is increased on cell surface. (G) LDL binding, endocytosis, and subsequent degradation. (H) Intracellular cholesterol increase toward cellular baseline. (I) Plasma LDL levels decrease.