Ezetimibe: efficacy and safety in clinical trials

Abstract

Aims: To review clinical trials establishing the efficacy and safety of ezetimibe 10 mg once daily, as monotherapy and co-administered with statins, for the treatment of hypercholesterolemia. Methods and results: As monotherapy, ezetimibe produced reductions in low-density lipoprotein cholesterol (LDL-C) of approximately 18% ( \(P\ {<}\ 0{\cdot}01\) compared with placebo). As add-on therapy for patients who failed to meet target reductions with statin monotherapy, the addition of ezetimibe produced a 21·4% additional reduction in LDL-C compared with statin monotherapy ( \(P\ {<}\ 0{\cdot}001\) ). Addition of ezetimibe to statin therapy also significantly improved high-density lipoprotein cholesterol and triglyceride levels compared with statin monotherapy ( \(P\ {<}\ 0{\cdot}05\) , \(P\ {<}\ 0{\cdot}001\) , respectively). In four studies in which ezetimibe 10 mg was co-administered with simvastatin, atorvastatin, pravastatin, or lovastatin at different dosages, reductions in LDL-C levels with co-administration were significantly greater than those obtained with the corresponding statin monotherapy dose. Ezetimibe plus 10 mg of simvastatin or atorvastatin produced LDL-C reductions comparable to 80 mg of the respective statin monotherapy. In all the clinical trials, ezetimibe was well tolerated, with a safety profile comparable to that of statin monotherapy and to that of placebo. Drug-drug interactions have not been observed when ezetimibe is given concomitantly with statins, fenofibrate, oral contraceptives, or a number of other commonly administered drugs. Conclusion: In the phase II and phase III clinical trial development program, ezetimibe has been shown to be an effective and safe new option for treating hypercholesterolemia even in difficult-to-treat populations such as homozygous and heterozygous familial hypercholesterolemia and sitosterolemia.