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.)

Background— Retrospective studies have suggested that patients with a low transvalvular gradient in the presence of an aortic valve area <1.0 cm 2 and normal ejection fraction may represent a subgroup with an advanced stage of aortic valve disease, reduced stroke volume, and poor prognosis requiring early surgery. We therefore evaluated the outcome of patients with low-gradient “severe” stenosis (defined as aortic valve area <1.0 cm 2 and mean gradient ≤40 mm Hg) in the prospective Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study. Methods and Results— Outcome in patients with low-gradient “severe” aortic stenosis was compared with outcome in patients with moderate stenosis (aortic valve area 1.0 to 1.5 cm 2 ; mean gradient 25 to 40 mm Hg). The primary end point of aortic valve events included death from cardiovascular causes, aortic valve replacement, and heart failure due to aortic stenosis. Secondary end points were major cardiovascular events and cardiovascular death. In 1525 asymptomatic patients (mean age, 67±10 years; ejection fraction, ≥55%), baseline echocardiography revealed low-gradient severe stenosis in 435 patients (29%) and moderate stenosis in 184 (12%). Left ventricular mass was lower in patients with low-gradient severe stenosis than in those with moderate stenosis (182±64 versus 212±68 g; P <0.01). During 46 months of follow-up, aortic valve events occurred in 48.5% versus 44.6%, respectively ( P =0.37; major cardiovascular events, 50.9% versus 48.5%, P =0.58; cardiovascular death, 7.8% versus 4.9%, P =0.19). Low-gradient severe stenosis patients with reduced stroke volume index (≤35 mL/m 2 ; n=223) had aortic valve events comparable to those in patients with normal stroke volume index (46.2% versus 50.9%; P =0.53). Conclusions— Patients with low-gradient “severe” aortic stenosis and normal ejection fraction have an outcome similar to that in patients with moderate stenosis.