Cardiovascular outcome trial · N Engl J Med 2008
SEAS trial
Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis.
The bottom line
In patients with mild-to-moderate asymptomatic aortic stenosis, simvastatin plus ezetimibe did not reduce the composite of aortic-valve and ischemic cardiovascular events, though it reduced ischemic events alone and was associated with more cancer cases.
No significant benefitUS status: US-approved
At a glance
- Medicine
- 40 mg of simvastatin plus 10 mg of ezetimibe daily
- Compared with
- placebo
- People
- 1,873
- Who took part
- 1873 patients with mild-to-moderate, asymptomatic aortic stenosis
- Design
- randomized, double-blind trial
- Follow-up
- median follow-up of 52.2 months
- Main question
- 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
Main result
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)
Other results
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. 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).
Safety
Cancer occurred more frequently in the simvastatin-ezetimibe group (105 vs. 70, P=0.01).
In the trial's own words
“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).”
Quoted from the abstract of N Engl J Med 2008, checked word for word against PubMed. PubMed 18765433 · Full paper (DOI)
How this medicine works, where it stands and what it costs: Ezetimibe (Zetia)
Common questions
What did the SEAS trial find?
In patients with mild-to-moderate asymptomatic aortic stenosis, simvastatin plus ezetimibe did not reduce the composite of aortic-valve and ischemic cardiovascular events, though it reduced ischemic events alone and was associated with more cancer cases.
Who was in SEAS?
1,873 people. 1873 patients with mild-to-moderate, asymptomatic aortic stenosis.
What was SEAS's main result?
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)
Related trials
- SHARP (2011)In patients with moderate-to-severe chronic kidney disease, lowering LDL cholesterol with simvastatin plus ezetimibe safely reduced major atherosclerotic events compared with placebo.
- IMPROVE-IT (2015)Adding ezetimibe to statin therapy after acute coronary syndrome modestly reduces cardiovascular events beyond statin alone, with similar safety.
- EWTOPIA 75 (2019)In patients aged 75 or older with elevated LDL-C and no history of coronary disease, adding ezetimibe to usual care reduced cardiovascular events, though open-label design, early termination, and follow-up issues warrant cautious interpretation of the benefit's magnitude.
- RACING (2022)In patients with atherosclerotic cardiovascular disease, moderate-intensity rosuvastatin plus ezetimibe was non-inferior to high-intensity rosuvastatin alone for 3-year cardiovascular outcomes, achieved more patients with LDL under 70 mg/dL, and caused less drug intolerance-related discontinuation or dose reduction.
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