Ezetimibe's effect on platelet aggregation and LDL tendency to peroxidation in hypercholesterolaemia as monotherapy or in addition to simvastatin

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Statins demonstrate a pleiotropic effect which contributes beyond the hypocholesterolaemic effect to prevent atherosclerosis. WHAT THIS STUDY ADDS: Ezetimibe has an antioxidative effect when given as monotherapy or as an add-on to the statin, simvastatin. AIMS To investigate the effect of lowering low-density lipoprotein-cholesterol (LDL-C) on platelet aggregation and LDL tendency to peroxidation by ezetimibe alone or with simvastatin in hypercholesterolaemia. METHODS: Sixteen patients with LDL-C >3.4 mmol l(-1) received ezetimibe for 3 months (Part I). Twenty-two patients on fixed simvastatin dose with LDL-C >2.6 mmol l(-1) were enrolled (Part II). Part II patients continued simvastatin treatment 20 mg day(-1) for 6 weeks, then received 20 mg day(-1) simvastatin combined with ezetimibe 10 mg day(-1) for another 6 weeks. The tendency of LDL to peroxidation measured by lag time in minutes required for initiation of LDL oxidation and by LDL oxidation at maximal point (plateau) was measured before and after ezetimibe treatment. RESULTS: Part I: Ezetimibe 10 mg daily for 3 months decreased plasma LDL-C level 16% (P = 0.002), prolonged lag time to LDL oxidation from 144 +/- 18 min to 195 +/- 16 min (P < 0.001), decreasing maximal aggregation from 83 +/- 15% to 60 +/- 36% (P = 0.04). Part II: Serum level LDL-C decreased 23% (P = 0.02) and lag time in minutes to LDL oxidation was prolonged from 55.9 +/- 16.5 to 82.7 +/- 11.6 (P < 0.0001) using combined simvastatin-ezetimibe therapy. There were no differences in platelet aggregation. CONCLUSIONS: Ezetimibe was associated with decreased platelet aggregation and LDL tendency to peroxidation. Treatment with ezetimibe in addition to simvastatin has an additive antioxidative effect on LDL.