Valvular heart diseaseObserved and Predicted Reduction of Ischemic Cardiovascular Events in the Simvastatin and Ezetimibe in Aortic Stenosis Trial
Section snippets
Methods
The SEAS study design and main outcome have been published.1, 2 In short, men and women (45 to 85 years of age) with asymptomatic mild-to-moderate AS (Doppler measured JV ≥2.5 and ≤4.0 m/s) and the absence of heart conditions requiring therapy at baseline were included. Patients with known coronary, cerebral, or peripheral arterial disease, diabetes mellitus, endocrine disorders, or active liver disease or patients taking/deemed to require lipid-lowering therapy to decrease atherosclerotic
Results
A total of 1,570 patients in the SEAS trial who had complete data for baseline JV, baseline and 1-year low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and apolipoprotein B measurements, and no ICEs during the first year were included in the main analyses. A special analysis with time-varying covariates was also performed in those 1,763 patients who had a valid baseline assessment of peak aortic JV measured at the core laboratory. Patient baseline characteristics were
Discussion
The present analysis demonstrates that ICE risk decreases in SEAS were greater in patients with less severe AS, as reflected by lower baseline JV, and were associated with changes in LCs. In contrast, ICE risk was not related to LC changes in patients with more severe AS. ICE risk decreases were also well predicted by changes in all LCs in patients with less severe AS. Compared to the CTT meta-analysis,3 a decrease in ICE risk of approximately 43% was predicted for an average decrease in
Acknowledgment
Thomas Musliner, MD, Jean-Louis Marchal, PhD, Joanne Tomassini, PhD, and Nigel Dodd, MSc, are gratefully acknowledged for contributing helpful comments, assistance in writing this report, and/or statistical support.
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2014, AtherosclerosisCitation Excerpt :These agents are contraindicated in patients with serum TG levels >400 mg/dL [109,115,116]. In the SEAS trial, despite a 53% reduction in LDL-C, ezetimibe 10 mg plus simvastatin 40 mg did not reduce the primary composite endpoint of major aortic-valve-related events (AVE) and ischemic cardiovascular events (ICE) significantly more than placebo (35.3% vs 38.2%, respectively; P = 0.59) during 4.4 years of therapy in patients (n = 1873) with mild-to-moderate AS, and without known CHD [34]. For the secondary endpoints, there was no significant difference in AVE (aortic valve replacement, death from cardiovascular causes, hospitalization for heart failure) (P = 0.73); however ICE (cardiovascular death, non-fatal acute myocardial infarction, coronary artery bypass grafting, percutaneous coronary intervention, hospitalization for unstable angina pectoris, non-hemorrhagic stroke) was significantly reduced (22%; P = 0.02) by ezetimibe plus simvastatin vs placebo.
This work was supported by Merck/Schering-Plough Pharmaceuticals, Inc., North Wales, Pennsylvania.