FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Previous Volume 358:1431-1443 April 3, 2008 Number 14 Next

	Full Text PDF PDA Full Text PowerPoint Slide Set CME Exam Supplementary Material Editorial by Brown, B. G. Editorial by Drazen, J. M. Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited E-mail When Letters Appear Related Article PubMed Citation

ABSTRACT

Background Ezetimibe, a cholesterol-absorption inhibitor, reduces levels of low-density lipoprotein (LDL) cholesterol when added to statin treatment. However, the effect of ezetimibe on the progression of atherosclerosis remains unknown.

Methods We conducted a double-blind, randomized, 24-month trial comparing the effects of daily therapy with 80 mg of simvastatin either with placebo or with 10 mg of ezetimibe in 720 patients with familial hypercholesterolemia. Patients underwent B-mode ultrasonography to assess the intima–media thickness of the walls of the carotid and femoral arteries. The primary outcome measure was the change in the mean carotid-artery intima–media thickness, which was defined as the average of the means of the far-wall intima–media thickness of the right and left common carotid arteries, carotid bulbs, and internal carotid arteries.

Results The primary outcome, the mean (±SE) change in the carotid-artery intima–media thickness, was 0.0058±0.0037 mm in the simvastatin-only group and 0.0111±0.0038 mm in the simvastatin-plus-ezetimibe (combined-therapy) group (P=0.29). Secondary outcomes (consisting of other variables regarding the intima–media thickness of the carotid and femoral arteries) did not differ significantly between the two groups. At the end of the study, the mean (±SD) LDL cholesterol level was 192.7±60.3 mg per deciliter (4.98±1.56 mmol per liter) in the simvastatin group and 141.3±52.6 mg per deciliter (3.65±1.36 mmol per liter) in the combined-therapy group (a between-group difference of 16.5%, P<0.01). The differences between the two groups in reductions in levels of triglycerides and C-reactive protein were 6.6% and 25.7%, respectively, with greater reductions in the combined-therapy group (P<0.01 for both comparisons). Side-effect and safety profiles were similar in the two groups.

Conclusions In patients with familial hypercholesterolemia, combined therapy with ezetimibe and simvastatin did not result in a significant difference in changes in intima–media thickness, as compared with simvastatin alone, despite decreases in levels of LDL cholesterol and C-reactive protein. (ClinicalTrials.gov number, NCT00552097 [ClinicalTrials.gov] .)

Source Information

From the Academic Medical Center, Amsterdam (J.J.P.K., F.A., E.S.G.S., A.H.Z., M.D.T., R.D., E.G.); the University Medical Center, Utrecht (M.L.B., F.L.J.V.); Radboud University Nijmegen Medical Center, Nijmegen (A.F.H.S.); and Erasmus Medical Center, Rotterdam (E.J.G.S.) — all in the Netherlands; the Metabolic and Atherosclerosis Research Center, Cincinnati (E.A.S.); Department of Medicine, Montreal University, Montreal (D.G.); Schering-Plough Research Institute, Kenilworth, NJ (E.P.V.); and Cape Heart Center, Cape Town, South Africa (A.D.M.).

This article (10.1056/NEJMoa0800742) was published at www.nejm.org on March 30, 2008.

Address reprint requests to Dr. Kastelein at the Department of Vascular Medicine, Academic Medical Center, Meibergdreef 9, P.O. Box 22660, 1100 DD Amsterdam, the Netherlands, or at j.j.kastelein{at}amc.uva.nl.

Full Text of this Article

This article has been cited by other articles:

• Jackevicius, C. A., Tu, J. V., Ross, J. S., Ko, D. T., Krumholz, H. M. (2008). Use of Ezetimibe in the United States and Canada. NEJM 358: 1819-1828 [Abstract] [Full Text]