**3. Conclusion**

Fenofibrate is a generalized, PPAR-α-mediated, serum lipid-lowering agent. In this chapter, the pleiotropic effects of fenofibrate other than serum lipid-lowering actions were primarily reviewed. Concerning to the anti-inflammatory actions, we examined the effects of fenofibrate in patients with a representative inflammatory disorder, RA. Although there were no significant changes in inflammation parameters including CRP and ESR, improvement in the ΔVAS and PSL dose was achieved in patients receiving fenofibrate. In particular, improvement in the ΔVAS was significantly correlated with a reduction in the ΔCRP level, suggesting that the anti-inflammatory effects of fenofibrate may contribute the improvement in the patient's quality of life (QOL).

In Japan, infectious diseases have been the major causes of death in patients with RA (Souen, 2007; Shinomiya et al., 2008). However, the proportion of cardiovascular events represented by cerebral/myocardial infarction has been increasing, probably because of the changes in life-style (Goto et al., 2008a). So, fenofibrate with lipid-lowering, antiinflammatory and anti-oxidant actions may be appropriate for reducing disturbances of lipid metabolism and also homeostasis in Japanese patients with RA.

With respect to antioxidant actions, fenofibrate, but not statin increased the plasma level of ubiquinol-10: a family of CoQ10. As fenofibrate exhibits antioxidant actions, combination

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therapy with fenofibrate and statins may be useful for achieving anti-aging effects and reducing oxidative stress. However, the evaluation methods for antioxidant activity in human should be strictly reviewed in the near future.

The serum uric acid-reducing actions of fenofibrate are regarded as one of its characteristic pleiotropic effects. The action mechanism may be mediated by a uric acid transporter, URAT1, but not by PPAR-. This may suggest that among fibrate preparations fenofibrate may be favorably administered to the patients with high serum TG and high uric acid levels, as no other fibrate preparations can reduce the serum level of uric acid.

The large-scale clinical study of fenofibrate (FIELD) showed that early administration to "primary prevention" diabetics without a history of cardiovascular events inhibited the onset of cardiovascular events. Furthermore, the DAIS, FIELD, and ACCORD-EYE studies suggested that early fenofibrate administration to all diabetics with dyslipidemia should inhibit the deterioration of diabetic complications regardless of the duration of disease or risk of events.

Fenofibrate shows pleiotropic actions, especially a variety of clinical effects that may not be achieved by statins. This agent may be useful for inhibiting the deterioration of arteriosclerosis, and may play a role as an anti-aging panacea if properly used.
