In reply: I agree with Montgomery that cardiovascular disease (CVD) outcomes are required to determine the role of ezetimibe. The Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) trial (in which patients with aortic stenosis were treated for 52.2 months with statin plus ezetimibe or statin plus placebo) showed a 4.7% reduction in ischaemic CVD events in the ezetimibe group (P = 0.02; number needed to treat, 23), driven by a reduced need for coronary artery bypass grafting.1 In contrast to previous trials showing regression of atherosclerosis in response to statin therapy, baseline carotid intima media thickness (CIMT) levels in the ENHANCE (Ezetimibe and Simvastatin in Hypercholesterolemia Enhances Atherosclerosis Regression) trial were normal, due to previous statin therapy. This is likely to account for the lack of change in CIMT with ezetimibe treatment in the ENHANCE trial.2 As no placebo group was included, neither lack of benefit nor harm from ezetimibe therapy can be inferred.2
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- 4. Gómez-Garre D, Muñoz-Pacheco P, González-Rubio ML, et al. Ezetimibe reduces plaque inflammation in a rabbit model of atherosclerosis and inhibits monocyte migration in addition to its lipid-lowering effect. Br J Pharmacol 2009; 156: 1218-1227.
- 5. Dietrich T, Hucko T, Bourayou R, et al. High resolution magnetic resonance imaging in atherosclerotic mice treated with ezetimibe. Int J Cardiovasc Imaging 2009; 25: 827-836.
- 6. Villines TC, Stanek EJ, Devine PJ, et al. The ARBITER 6-HALTS Trial (Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol 6 — HDL and LDL Treatment Strategies in Atherosclerosis). Final results and the impact of medication adherence, dose, and treatment duration. J Am Coll Cardiol 2010; 55: 2721-2726.
Ian Hamilton-Craig has served on lipid advisory boards for Merck Sharp and Dohme, Solvay/Abbott and AstraZeneca, and has received speaker fees and reimbursement for travel/accommodation expenses to attend scientific meetings from these companies. He has also received honoraria from these companies and from Novartis, Pfizer, Schering Plough and Servier for presentations at postgraduate scientific meetings.