Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis

Anne B. Rossebø, 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 Skjærpe, Kristian Wachtell, Ronnie Willenheimer

    Research output: Contribution to journalArticlepeer-review


    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 aorticvalve 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. ( number, NCT00092677.) Copyright © 2008 Massachusetts Medical Society. All rights reserved.
    Original languageEnglish
    Pages (from-to)1343-1356
    Number of pages13
    JournalNew England Journal Of Medicine
    Issue number13
    Publication statusPublished - 25 Sept 2008


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