Inhibition of microsomal triglyceride transfer protein alone or with ezetimibe in patients with moderate hypercholesterolemia

Background Many patients with coronary heart disease do not achieve recommended LDL-cholesterol levels, due to either intolerance or inadequate response to available lipid- lowering therapy. Microsomal triglyceride transfer protein (MTP) inhibitors might provide an alternative way to lower LDL- cholesterol levels. We tested the safety and LDL- cholesterol- lowering efficacy of an MTP inhibitor, AEGR- 733 ( Aegerion Pharmaceuticals Inc., Bridgewater, NJ), alone and in combination with ezetimibe. Methods We performed a multicenter, double- blind, 12- week trial, which included 84 patients with hypercholesterolemia. Patients were randomly assigned ezetimibe 10 mg daily ( n = 29); AEGR- 733 5.0 mg daily for the first 4 weeks, 7.5 mg daily for the second 4 weeks and 10 mg daily for the last 4 weeks ( n = 28); or ezetimibe 10 mg daily and AEGR- 733 administered with the dose titration described above ( n = 28). Results Ezetimibe monotherapy led to a 20 - 22% decrease in LDLcholesterol concentrations. AEGR- 733 monotherapy led to a dosedependent decrease in LDL- cholesterol concentration: 19% at 5.0 mg, 26% at 7.5 mg and 30% at 10 mg. Combined therapy produced similar but larger dose- dependent decreases ( 35%, 38% and 46%, respectively). The number of patients who discontinued study drugs owing to adverse events was five with ezetimibe alone, nine with AEGR- 733 alone, and four with combined ezetimibe and AEGR- 733. Discontinuations from AEGR- 733 were due primarily to mild transaminase elevations. Conclusions Inhibition of LDL production with low- dose AEGR- 733, either alone or in combination with ezetimibe, could be an effective therapeutic option for patients unable to reach target LDL- cholesterol levels.