Statins: Pharmacology, medical uses and clinical outcomes

The use of statins has recently attracted the attention of clinicians. Indeed, statins are probably the most common chronic treatment used for cardiovascular disease (18 million prescription purchase in France and 173.7 million in United States, per year). Moreover, their so-called pleiotropic effects open the gates to much larger medical applications. However, it is still difficult to predict the individual's response to statin therapy. Recent research has shown that variants of candidate genes affect statin efficacy and safety. Clinicians often assume that symptoms occurring with statins are caused by statins, encouraging discontinuation. But so far, only asymptomatic liver enzymes, muscle aches and development of new-onset diabetes mellitus has been proven to be related to statin therapy. To lower cholesterol levels, clinicians could prescribe statin monotherapy or a statin in combination with another agent. There are potential benefits to treating with multiple agents, such as the different mechanisms of action of other lipid-modifying agents, may be a solution against the adverse effects of statins and their intolerance. Given their pleiotropic effects, statins could be used in non-dyslipidemic diseases. In this chapter, we will first examine the properties of statins including their structure, metabolism, and potency. We will also look at the pharmacogenomics of statins as well their mechanisms of action from their lipid-lowering effects to the more complex anti-inflammatory, immunomodulatory, anti-thrombotic, and anti-oxidant properties found independently of the lipid-lowering properties. Following this, we will review the potential adverse effects of statins including the mechanisms leading to myopathy and new-onset diabetes mellitus. In this regard, we will assess the benefits and harmful intensification of statin monotherapy compared to the combination of statins and other lipid-modifying medications. Then, we will discuss the guidelines regarding the use of statins in the well-established scope of cardiovascular diseases. Finally, we will review the potential benefits of statins in non-dyslipdemic disorders in chronic diseases such as rheumatoid arthritis, venous thromboembolism, and polycystic ovary syndrome, as well as in critical illnesses such as sepsis, acute lung injury / acute respiratory distress syndrome or after subarachnoidal hemorrhage. We will particularly focus on the latter..