Intensive Lipid Lowering with Simvastatin and Ezetimibe in Aortic Stenosis.
Rossebo, Anne B. M.D.; Pedersen, Terje R. M.D., Ph.D.; Boman, Kurt M.D., Ph.D.; Brudi, Philippe M.D.; Chambers, John B. M.D.; Egstrup, Kenneth M.D., Ph.D.; Gerdts, Eva M.D., Ph.D.; Gohlke-Barwolf, Christa M.D.; Holme, Ingar Ph.D.; Kesaniemi, Antero Y. M.D., Ph.D.; Malbecq, William Ph.D.; Nienaber, Christoph A. M.D., Ph.D.; Ray, Simon M.D.; Skjaerpe, Terje M.D., Ph.D.; Wachtell, Kristian M.D., Ph.D.; Willenheimer, Ronnie M.D., Ph.D.; the SEAS Investigators *
[Article]
New England Journal of Medicine.
359(13):1343-1356, September 25, 2008.
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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.)
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