Literature DB >> 18765433

Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis.

Anne B Rossebø1, Terje R Pedersen, Kurt Boman, Philippe Brudi, John B Chambers, Kenneth Egstrup, Eva Gerdts, Christa Gohlke-Bärwolf, Ingar Holme, Y Antero Kesäniemi, William Malbecq, Christoph A Nienaber, Simon Ray, Terje Skjaerpe, Kristian Wachtell, Ronnie Willenheimer.   

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.) 2008 Massachusetts Medical Society

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Year:  2008        PMID: 18765433     DOI: 10.1056/NEJMoa0804602

Source DB:  PubMed          Journal:  N Engl J Med        ISSN: 0028-4793            Impact factor:   91.245


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