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Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis

Rossebo, Anne B.; Pedersen, Terje R.; Boman, Kurt; Brudi, Philippe; Chambers, John B.; Egstrup, Kenneth; Gerdts, Eva; Gohlke-Barwolf, Christa; Holme, Ingar and Kesaniemi, Y. Antero, et al. (2008) In New England Journal of Medicine 359(13). p.1343-1356
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... (More)
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.). (Less)
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New England Journal of Medicine
volume
359
issue
13
pages
1343 - 1356
publisher
Massachusetts Medical Society
external identifiers
  • wos:000259440900005
  • scopus:52649120889
ISSN
0028-4793
DOI
10.1056/NEJMoa0804602
language
English
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yes
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11d61d1f-088e-4972-9e00-51461ef72484 (old id 1246857)
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2008-11-19 09:40:59
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2017-09-10 03:46:38
@article{11d61d1f-088e-4972-9e00-51461ef72484,
  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.).},
  author       = {Rossebo, Anne B. and Pedersen, Terje R. and Boman, Kurt and Brudi, Philippe and Chambers, John B. and Egstrup, Kenneth and Gerdts, Eva and Gohlke-Barwolf, Christa and Holme, Ingar and Kesaniemi, Y. Antero and Malbecq, William and Nienaber, Christoph A. and Ray, Simon and Skjaerpe, Terje and Wachtell, Kristian and Willenheimer, Ronnie},
  issn         = {0028-4793},
  language     = {eng},
  number       = {13},
  pages        = {1343--1356},
  publisher    = {Massachusetts Medical Society},
  series       = {New England Journal of Medicine},
  title        = {Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis},
  url          = {http://dx.doi.org/10.1056/NEJMoa0804602},
  volume       = {359},
  year         = {2008},
}