Efficacy and safety of ezetimibe coadministered with pravastatin in patients with primary hypercholesterolemia: a prospective, randomized, double-blind trial

Aims To evaluate the efficacy and safety of ezetimibe 10 mg administered with pravastatin in patients with primary hypercholesterolemia. Methods and results After dietary stabilization, 2-12 week screening/washout period, and 4-week, single-blind, placebo lead-in period, 538 patients with baseline LDL-C greater than or equal to3.8 to less than or equal to6.5 mmol/l and TG less than or equal to4.0 mmol/l were randomized to one of eight possible treatments administered daily for 12 weeks: ezetimibe 10 mg; pravastatin 10, 20, or 40 mg; ezetimibe 10 mg plus pravastatin 10, 20, or 40 mg; or placebo. The primary efficacy endpoint was percent reduction in LDL-C from baseline to study endpoint for ezetimibe 10 mg plus pravastatin (pooled doses) compared to pravastatin alone (pooled doses) and ezetimibe alone. The combined use of ezetimibe and pravastatin resulted in significant incremental reductions in LDL-C and TG compared to pooled pravastatin atone (p<0.01). Coadministration therapy reduced LDL-C by 34-41%, TG by 21-23%, and increased HDL-C by 7.8-8.4%, depending on the dose of pravastatin. The combined regimen was well tolerated, with a safety profile similar to pravastatin atone and placebo. Conclusions When coadministered with pravastatin, ezetimibe provided significant incremental reductions in LDL-C and TG and was welt tolerated with a safety profile similar to pravastatin alone. (C) 2003 The European Society of Cardiology. Published by Elsevier Science Ltd. All rights reserved.