Effects of ezetimibe on plasma lipoproteins in severely hypercholesterolemic patients treated with regular LDL-apheresis and statins.

Ezetimibe, a cholesterol absorption inhibitor, can be combined with statins to lower LDL-cholesterol. We evaluated additional ezetimibe (10 mg/day) in a placebo-controlled, double blind, randomized cross-over study in 20 patients (age 56+/-9 years, m:f 10:10, BMI 27.5+/-4.0 kg/m(2)) suffering from severe hypercholesterolemia and CHD who were treated by statins and regular LDL-apheresis. Lipoproteins (cholesterol, triglycerides, LDL-cholesterol, HDL-cholesterol, VLDL-cholesterol, VLDL-triglycerides, lipoprotein(a)) were determined twice (before and during ezetimibe/placebo, each given for 5 weeks), dietary behaviour was analyzed once (3-days-protocol) during each treatment period. During ezetimibe the mean (+/-S.D.) preapheresis LDL-cholesterol concentration decreased from 159+/-26 mg/dl (4.11+/-0.67 mmol/l) to 133+/-28 mg/dl (3.44+/-0.72 mmol/l) (-16+/-11%, P<0.0001, Wilcoxon test) and the postapheresis LDL-cholesterol from 51+/-9 mg/dl (1.32+/-0.23 mmol/l) to 43+/-8 mg/dl (1.11+/-0.21 mmol/l) (-14+/-25%, P<0.05), while there was no significant change during placebo. Mean VLDL-cholesterol fell by 18+/-71% (P<0.05) during ezetimibe and was not significantly changed by placebo (+19+/-70%). Furthermore, during ezetimibe less plasma volume was treated (3725+/-1560 versus 3870+/-1549 ml, P<0.05). Ezetimibe had no effect on pre- and postapheresis triglyceride, HDL-cholesterol and lipoprotein(a) levels. The effect of ezetimibe was independent of the statin dose. Dietary behaviour did not change and no side effects were observed. Thus, in patients with severe LDL-hypercholesterolemia and CHD the addition of ezetimibe to intensive lipid lowering therapy (statins and LDL-apheresis) resulted in a further, clinically significant decrease of LDL-cholesterol.