PURPOSE OF REVIEW: Statins are the most widely prescribed class of drugs for cardiovascular (CV) disease (CVD) prevention due to their potent lipid-lowering effects. However, accumulating evidence demonstrates additional cardioprotective properties of statins mediated through pleiotropic mechanisms unrelated to cholesterol modulation. We aimed to discuss the pleiotropic effects of statins and their relevance to clinical outcomes in 2 reviews: Part I focuses on anti-inflammatory, antioxidant and immunomodulatory effects of statins, whereas Part II on statin-induced endothelial function improvement, plaque stabilization and anti-thrombotic effects. Part II also includes a clinical applications and future directions section. RECENT FINDINGS: A literature search was conducted in Embase, Scopus, web of science, PubMed and Cochrane Library databases for experimental and clinical studies investigating the effects of statins on inflammation, oxidative stress and immune function. Statins exert potent anti-inflammatory, antioxidant and immunomodulatory activities that can be linked to reduced CV events. Statins confer cardio protection via diverse pleiotropic pathways distinct from cholesterol modulation. Future directions involve optimizing regimens to maximize clinical benefits, addressing controversies, and exploring statins' therapeutic potential beyond CVD through non-lipid mechanisms. A comprehensive understanding of statins' pleiotropic profile will uncover new preventive strategies and therapeutic applications.

3rd Department of Medicine 1st Faculty of Medicine Charles University General University Hospital Prague Czech Republic

Applied Biomedical Research Center Basic Sciences Research Institute Mashhad University of Medical Sciences Mashhad Iran

Biotechnology Research Center Pharmaceutical Technology Institute Mashhad University of Medical Sciences Mashhad Iran

Centre for Research Impact and Outcome Chitkara College of Pharmacy Chitkara University Rajpura Punjab 140401 India

Department of Basic Medical Sciences Faculty of Medicine Abadan University of Medical Sciences Abadan Iran

Department of Nutritional Sciences and Dietetics International Hellenic University Thessaloniki 57400 Greece

School of Medicine European University Cyprus Nicosia 2404 Cyprus

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