Early Therapeutic Effects of Statins and Fibrates on Unstable Atherosclerotic Plaques

Rupture of unstable atherosclerotic plaques is the underlying pathophysiologic mechanism of acute coronary syndromes and thus also of perioperative myocardial ischemia. Lipid lowering drugs such as statins and fibrates have been shown to improve the outcomes of patients with atherosclerosis. This is not only mediated through their therapeutic actions on lipid metabolism, but relies on a multitude of pleiotropic effects of these substances. One of the most interesting of these effects is the stabilisation of atherosclerotic plaques. To investigate these effects in a perioperative setting, patients scheduled for thromboendarterectomy of the carotid artery will be recruited. They will be randomised to receive either atorvastatin 10mg/d, gemfibrozil 1200mg/d or placebo for two weeks preoperatively. Specimens of carotid plaques will be obtained intraoperatively. After microscopic characterisation of plaques, DNA-microarray analyses will be done to gain insights into the transcriptional regulation and expression profiles of various types of atherosclerotic plaques under different pharmacological circumstances (stable or unstable with statin/fibrate/placebo).