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Ezetimibe: efficacy and safety in clinical trials

C.M. Ballantyne*

Center for Cardiovascular Disease Prevention, Methodist DeBakey Heart Center, Baylor College of Medicine, Texas, U.S.A.

* Correspondance: Christie Ballantyne, MD, Section of Atherosclerosis and Lipoprotein Research, Baylor College of Medicine, 6565 Fannin Street, M.S. A-601, Suite A654B, Houston, Texas 77030, U.S.A.

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% ( 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 (). Addition of ezetimibe to statin therapy also significantly improved high-density lipoprotein cholesterol and triglyceride levels compared with statin monotherapy (, , 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.

Key Words: Cholesterol-lowering drugs • clinical trials • ezetimibe • low-density lipoprotein cholesterol • hyperlipidemia

References

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