Valvular heart disease
Design and Baseline Characteristics of the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) Study

https://doi.org/10.1016/j.amjcard.2006.10.064Get rights and content

Aortic valve stenosis and atherosclerotic disease have several risk factors in common, in particular, hypercholesterolemia. Histologically, the diseased valves appear to have areas of inflammation much like atherosclerotic plaques. The effect of lipid-lowering therapy on the progression of aortic stenosis (AS) is unclear, and there are no randomized treatment trials evaluating cardiovascular morbidity and mortality in such patients. The Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) Study is a randomized, double-blind, placebo-controlled, multicenter study of a minimum 4 years’ duration investigating the effect of lipid lowering with ezetimibe/simvastatin 10/40 mg/day in patients with asymptomatic AS with peak transvalvular jet velocity 2.5 to 4.0 m/s. Primary efficacy variables include aortic valve surgery and ischemic vascular events, including cardiovascular mortality, and second, the effect on echocardiographically evaluated progression of AS. The SEAS Study randomly assigned 1,873 patients (age 68 ± 10 years, 39% women, mean transaortic maximum velocity 3.1 ± 0.5 m/s) from 173 sites. Other baseline characteristics were mean blood pressure of 145 ± 20/82 ± 10 mm Hg (51% hypertensive); 55% were current or previous smokers; and most were overweight (mean body mass index 26.9 kg/m2). At baseline, mean total cholesterol was 5.7 ± 1.0 mmol/L (222 mg/dl), low-density lipoprotein cholesterol was 3.6 ± 0.9 mmol/L (139 mg/dl), high-density lipoprotein cholesterol was 1.5 ± 0.4 mmol/L (58 mg/dl), and triglycerides were 1.4 ± 0.7 mmol/L (126 mg/dl). The SEAS Study is the largest randomized trial to date in patients with AS and will allow determination of the prognostic value of aggressive lipid lowering in such patients.

Section snippets

Study aim

The primary objective of the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) Study is to investigate whether intensive lipid lowering with E/S combination therapy will reduce the need for aortic valve replacement and the risk of cardiovascular morbidity and mortality.

Patient population and study design

The SEAS Study is a multicenter, double-blind, randomized, placebo-controlled study. Eligible patients had asymptomatic AS defined as aortic valve thickening using echocardiographic evaluation accompanied by a Doppler-measured

Discussion

Baseline characteristics of the SEAS Study population show that most traditional risk factors for cardiovascular disease are increased, as seen in other large population studies of AS.1, 3 Because of important exclusion criteria being necessary for ethical reasons, the study population may appear as a selected one. Few patients have signs of metabolic syndrome (probably because of exclusion of patients with diabetes), high-density lipoprotein cholesterol level is relatively high, and the

Acknowledgement

We acknowledge the work done by all Merck clinical research staff in facilitating the study and the clinical investigators and study site staff.

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This work was supported by the pharmaceutical company MSP Singapore Company, LLC, Singapore, a partnership between Merck & Co., Inc., and the Schering-Plough Corporation.

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