An investigative look: selective cholesterol absorption inhibitors--embarking on a new standard of care.

Abstract

Phase 2 and 3 clinical trials evaluating the selective cholesterol absorption inhibitor ezetimibe have demonstrated that the drug is safe and effective, both as monotherapy and in combination with several statins. Placebo-controlled phase 2 studies of 8 and 12 weeks' duration established that ezetimibe monotherapy achieved maximum cholesterol lowering at doses between 10 and 20 mg daily. Additional dose-scheduling studies demonstrated that evening dosing was only slightly more effective than morning dosing, and that the drug could be taken with or without food without any impairment in efficacy. These studies also showed that ezetimibe was well tolerated, with side effects no different from those seen with placebo. Short-term, early phase 2 studies evaluating the coadministration of ezetimibe and a number of different statins found that coadministration was safe, that ezetimibe did not alter the pharmacokinetics of the statins or vice versa, and that the reductions in low-density lipoprotein cholesterol were complementary, with the degree of cholesterol lowering seen with ezetimibe monotherapy maintained when it was given in combination with a statin. These studies indicate that combination therapy with ezetimibe and a starting dose of a statin produces a reduction in cholesterol levels equivalent to that seen with an 8-fold higher statin dose. Larger, long-term phase 3 trials confirmed the efficacy and safety of the 10-mg dose and also demonstrated that ezetimibe monotherapy is an excellent alternative for patients who cannot tolerate statins.