TY - JOUR
T1 - Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis
AU - Rossebø, Anne B
AU - Pedersen, Terje R
AU - Boman, Kurt
AU - Brudi, Philippe
AU - Chambers, John B
AU - Egstrup, Kenneth
AU - Gerdts, Eva
AU - Gohlke-Bärwolf, Christa
AU - Holme, Ingar
AU - Kesäniemi, Y Antero
AU - Malbecq, William
AU - Nienaber, Christoph A
AU - Ray, Simon
AU - Skjaerpe, Terje
AU - Wachtell, Kristian
AU - Willenheimer, Ronnie
AU - Schmidt, SEAS Investigator, Erik Berg
AU - Espersen, SEAS Investigator, Geert
AU - SEAS Investigators
N1 - 2008 Massachusetts Medical Society
PY - 2008
Y1 - 2008
N2 - 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.)
AB - 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.)
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Alanine Transaminase
KW - Anticholesteremic Agents
KW - Aortic Valve Stenosis
KW - Aspartate Aminotransferases
KW - Azetidines
KW - Cardiovascular Diseases
KW - Cholesterol, LDL
KW - Coronary Artery Bypass
KW - Disease Progression
KW - Double-Blind Method
KW - Drug Therapy, Combination
KW - Female
KW - Follow-Up Studies
KW - Heart Valve Prosthesis Implantation
KW - Humans
KW - Kaplan-Meiers Estimate
KW - Male
KW - Neoplasms
KW - Simvastatin
KW - Treatment Outcome
U2 - 10.1056/NEJMoa0804602
DO - 10.1056/NEJMoa0804602
M3 - Journal article
SN - 0028-4793
VL - 359
SP - 1343
EP - 1356
JO - The New England Journal of Medicine
JF - The New England Journal of Medicine
ER -