Homocysteine and lipid lowering agents. A comparison between atorvastatin and fenofibrate in patients with mixed hyperlipidemia

Background: Hyperhomocysteinemia is a risk factor for cardiovascular disease. Elevation in homocysteine levels has recently been demonstrated during lipid lowering treatment with fibrates. We compared the effect of a statin and a fibrate (atorvastatin and fenofibrate) on plasma levels of homocysteine and other thiol compounds in hyperlipidemic patients. Method and results: The study was of open randomized, parallel design with a preliminary screening phase, and a 6 week placebo period. After the placebo period, patients were allocated randomly to atorvastatin or fenofibrate for a 6 month period. Plasma thiols were assayed by high pressure liquid chromatography with fluorescence detection. There were 29 patients in the fenofibrate group and 24 in the atorvastatin group. Fenofibrate induced a significant increase in both homocysteine and cysteine plasma levels (+35.8 and +18%, respectively, P<0.0001); by contrast, cysteinylglycine remained stable. There were no significant changes in any thiol compounds in the atorvastatin group. Both treatments induced a significant decrease in uric acid, although fenofibrate was noticeably more effective than atorvastatin (−22.8 and −6.4%, respectively). Fenofibrate induced a non-significant increase in creatinine (12%) while atorvastatin reduced it (4.7%, NS). Conclusion: Our study confirms that the induction of elevations in plasma homocysteine and cysteine levels are a distinct feature of the pleiotropic effects of fibrates. Further studies are needed not only to investigate the potential deleterious effects of this modification, but also to define the specific mechanism which underlies such fibrate-mediated action.