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Published at www.nejm.org September 2, 2008 (10.1056/NEJMoa0804602)

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ABSTRACT

Background Hyperlipidemia has been suggested as a risk factor for stenosis of the aortic valve, but lipid-lowering studies have had conflicting results.

Methods We conducted a randomized, double-blind trial involving 1873 patients with mild-to-moderate, asymptomatic aortic stenosis. The patients received either 40 mg of simvastatin plus 10 mg of ezetimibe or placebo daily. The primary outcome was a composite of major cardiovascular events, including death from cardiovascular causes, aortic-valve replacement, nonfatal myocardial infarction, hospitalization for unstable angina pectoris, heart failure, coronary-artery bypass grafting, percutaneous coronary intervention, and nonhemorrhagic stroke. Secondary outcomes were events related to aortic-valve stenosis and ischemic cardiovascular events.

Results During a median follow-up of 52.2 months, the primary outcome occurred in 333 patients (35.3%) in the simvastatin–ezetimibe group and in 355 patients (38.2%) in the placebo group (hazard ratio in the simvastatin–ezetimibe group, 0.96; 95% confidence interval [CI], 0.83 to 1.12; P=0.59). Aortic-valve replacement was performed in 267 patients (28.3%) in the simvastatin–ezetimibe group and in 278 patients (29.9%) in the placebo group (hazard ratio, 1.00; 95% CI, 0.84 to 1.18; P=0.97). Fewer patients had ischemic cardiovascular events in the simvastatin–ezetimibe group (148 patients) than in the placebo group (187 patients) (hazard ratio, 0.78; 95% CI, 0.63 to 0.97; P=0.02), mainly because of the smaller number of patients who underwent coronary-artery bypass grafting. Cancer occurred more frequently in the simvastatin–ezetimibe group (105 vs. 70, P=0.01).

Conclusions Simvastatin and ezetimibe did not reduce the composite outcome of combined aortic-valve events and ischemic events in patients with aortic stenosis. Such therapy reduced the incidence of ischemic cardiovascular events but not events related to aortic-valve stenosis. (ClinicalTrials.gov number, NCT00092677 [ClinicalTrials.gov] .)

Source Information

The authors' affiliations are listed in the Appendix.

This article (10.1056/NEJMoa0804602) was published at www.nejm.org on September 2, 2008. It will appear in the September 25 issue of the Journal.

Address reprint requests to Dr. Rossebø at the Division of Cardiology, Aker University Hospital, Trondheimsveien 235, N-0514 Oslo, Norway, or at anne{at}rossebo.net.

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