3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) inhibit the biosynthesis of cholesterol. Statins have therefore become established in the treatment of hypercholesterolaemia and attained a central place in cardiovascular medicine because of their proven benefits in both primary and secondary prevention of cardiovascular events (for review see [1
Analyses of major trials, coupled with animal experimentation and studies in vitro
, have suggested that some of the benefits of statins may be due to multiple, pleiotropic effects independent of direct reductions in low density lipoprotein cholesterol (LDL-C). Such effects can include improvements in endothelial function, decreases in smooth muscle proliferation and vascular inflammation and antiplatelet actions (), as well as effects on other lipids and lipoproteins [2
]. Pleiotropic effects may play an important part in reducing cardiovascular mortality and morbidity [3
], and differences in the spectrum of such effects between members of the class could be relevant when formulating management plans for individual patients. Furthermore, different enzymes are involved in the metabolism of different statins, leading to unique drug–drug interaction profiles. Such differences are particularly important for patients at high risk of developing atherosclerosis, who are frequently polymedicated.
Table 1 Pleiotropic effects of statins. Adapted from Sadowitz et al. 
In an era in which clinicians are increasingly aware of the need to tailor therapeutic approaches to individual patients [5
], insight into the potential benefits of statins on factors other than LDL-C reduction is particularly important. Recent research, for example, has highlighted the potential of novel statin derivatives to improve the anti-inflammatory [6
] and antithrombotic [7
] effects of available statins.
Pitavastatin is a novel synthetic lipophilic statin shown to reduce serum concentrations of LDL-C and triglycerides, and increase high density lipoprotein cholesterol (HDL-C), in dyslipidaemic patients [8
]. At doses of 2–4 mg daily, pitavastatin has been shown to have a similar effect on LDL-C as atorvastatin 10–20 mg [10
], with greater effects on HDL-C [11
This paper reviews the main pleiotropic effects of pitavastatin on endothelial function, vascular inflammation, oxidative stress and thrombosis. Together with the direct effects of pitavastatin on serum LDL-C concentrations, pleiotropic effects not directly related to cholesterol synthesis may help to explain the unique pharmacological profile of this statin.
Publications included in this review were based mainly on a search of the PubMed and EMBASE databases carried out in December 2010. The strategy used was to search for English language publications on pitavastatin in ‘all fields’ on PubMed or in the ‘title/abstract’ field in EMBASE. This global search yielded a total of 756 articles (PubMed 329, EMBASE 427). After exclusion of foreign language references and duplicate entries, a total of 431 non-duplicate individual references were screened for relevance to the pleiotropic effects of pitavastatin. Screening removed all conference abstracts, review articles or correspondence (editorials and letters) and articles not relevant to the pleiotropic effects of pitavastatin, yielding a total of 134 relevant articles for further assessment. Relevant papers published after December 2010 were also included as appropriate. References were then grouped under category headings (endothelial function, inflammation and immunomodulation, oxidative stress and lipoprotein oxidation, effects of pitavastatin on lipids other than LDL-C, thrombosis and fibrinolysis, cardiovascular and organ-protective effects).