Effect of ezetimibe on low-density lipoprotein subtype distribution: results of a placebo-controlled, double-blind trial in patients treated by regular low-density lipoprotein apheresis and statins

Ezetimibe, a cholesterol absorption inhibitor, can be combined with statins to lower low-density lipoprotein (LDL) cholesterol. We have previously shown that ezetimibe can decrease LDL cholesterol by 16% even in patients treated by regular LDL apheresis and statins (Atherosclerosis. 2005;180:107-112). However, it is unclear whether ezetimibe decreases all LDL subfractions equally in patients with hypercholesterolemia. We therefore evaluated the effect of ezetimibe (5 weeks, 10 mg/d) on LDL subtype distribution in a placebo-controlled, double-blind randomized crossover study in 20 patients (age, 56 ± 9 years; body mass index, 27.5 ± 4 kg/m2) with severe hyperlipoproteinemia and coronary heart disease who are treated by statins and regular LDL apheresis. Both treatment periods (placebo and ezetimibe) were separated by a 5-week washout period. Low-density lipoprotein subtype distribution was determined at the end of each treatment period before apheresis by density gradient ultracentrifugation (LDL1, 1.020-1.024; LDL2, 1.025-1.029; LDL3, 1.030-1.034; LDL4, 1.035-1.040; LDL5, 1.041-1.047; LDL6, 1.048-1.057; LDL7, 1.058-1.066 g/mL). Overall, the LDL subtype distribution did not change significantly (large-buoyant LDL [LDL1 + LDL2], 17.2% ± 6.4% vs 16.3% ± 7.1%; intermediate LDL [LDL3 + LDL4], 49.3% ± 4.5% vs 48.2% ± 5.2%; small-dense LDL [LDL5 + LDL6 + LDL7], 33.5% ± 8.0% vs 35.5% ± 10% during placebo and ezetimibe treatments, respectively). With respect to the individual LDL subfractions, cholesterol was significantly (P < .05, Wilcoxon test) reduced by ezetimibe in LDL1 to LDL5 with a somewhat more pronounced reduction in larger LDL (mean ± SD, −20% ± 28%, −17% ± 32%, −14% ± 25%, −13% ± 27%, −11% ± 21%, −7% ± 21%, −4% ± 19%; median, −28%, −12%, −18%, −16%, −4%, −4%, −2% for LDL subfractions 1-7, respectively). We therefore conclude that ezetimibe decreases cholesterol in nearly all LDL subfractions. Although this was established in patients concomitantly treated with statins and apheresis, this may also hold true in other clinically relevant situations.