Lipid Lowering on Progression of Mild to Moderate Aortic Stenosis: Meta-analysis of the Randomized Placebo-Controlled Clinical Trials on 2344 Patients

Background: Aortic stenosis (AS) is believed to develop through an inflammatory similar to the atherosclerosis process. Based on findings from animal studies and uncontrolled clinical studies, lipid-lowering therapy with a statin is postulated to slow this process. Randomized trials, however, reported neutral results. This meta-analysis of randomized lipid trials on patients with AS examined the effects of treatment on AS progression and clinical outcomes. Methods: Echocardiographic measures of AS (aortic valve jet velocity, peak and mean valve gradients, and aortic valve area) were pooled and clinical outcomes were evaluated in 4 randomized placebo controlled trials (N = 2344). Results: Although active treatment with statin therapy was associated with highly significant 50% reduction in low-density lipoprotein cholesterol levels, there were no statistical differences between active and placebo groups in any of the echocardiographic indicators of AS severity: annual increase in AS velocity was 0.16 +/- 0.28 m/sec, and mean gradient was 2.8 +/- 3.0 mm Hg. Each trial reported no differences in clinical outcomes between the 2 treatment groups. Substantial events rates (6.6% aortic valve surgery and 1.2% cardiovascular deaths per year in SEAS with follow-up of 4.4 years and 5.8% aortic valve surgery and 0.7% cardiovascular deaths per year in ASTRONOMER over 3.5 years) were observed in these patients despite the relatively mild disease. Conclusion: The current data do not support the hypothesis that statin therapy reduces AS progression. Patients with mild to moderate AS may require closer follow-up because despite the less severe disease in these trials, event rates remain substantial.