July 27, 2010
By Nalini M. Rajamannan, M.D. and Asher Kimchi, MD
Vancouver, B.C., Canada - Until now all of the prospective trials testing the role of statins in aortic valve disease have been negative for the treatment of calcific aortic stenosis. These trials include SALTIRE, SEAS and Astronomer. RAAVE is the first study to evaluate the use of statins for calcific aortic valve disease in an open label study treating only patients with elevated LDL with moderate to severe aortic stenosis. The results of these studies demonstrated opposing effects of statins on the valve. In an Study by Nalini M. Rajamannan, M.D et al from Chicago, IL, USA, presented at the International Academy of Cardiology, 15th World Congress on Heart Disease, Annual Scientific Sessions 2010 in Vancouver, B.C., Canada , results combining SALTIRE and RAAVE demonstrated a positive benefit of slowing progression of aortic stenosis. The hypothesis tested whether LDL lowering from statin therapy was associated with slowing of the progression of the change in the aortic valve area (AVA). The study used the LDL-Density-Radius Theory and combined specific data points from the SALTIRE and the RAAVE studies. The hypothesis tested whether LDL lowering from statin therapy was associated with slowing of the progression of the change in the aortic valve area (AVA). The study used the LDL-Density-Radius Theory and combined specific data points from the SALTIRE and the RAAVE studies.
Nalini M. Rajamannan, M.D.
SALTIRE was a double-blind, placebo-controlled trial, in which patients with calcific aortic stenosis were randomly assigned to receive either 80 mg of atorvastatin daily or a matched placebo for 25 months. RAAVE was an open-label, prospective study where patients with asymptomatic moderate to severe aortic stenosis were treated with and without 20 mg of rosuvastatin according to the National Cholesterol Education Program Adult Treatment Panel III guidelines for 18 months. Echocardiographic and serum lipids were measured at the start of each study and at study conclusion. The study performed a combined analysis of SALTIRE and RAAVE using datapoints from each trial for the LDL levels and the aortic valve area (AVA)s. Because of the LDL-Density-Radius theorem we evaluated the % change in LDL to the % change in AVA in all patients treated with statin therapy using a one way ANOVA.
In those patients who received statin therapy in the combined data for SALTIRE and RAAVE a greater degree of LDL cholesterol lowering seen as the % change in LDL significantly associated with a lower change for aortic valve area demonstrating a slowing of progression with statin therapy (p<0.001 and R2=0.27). In summary, these findings suggest that statin therapy may have a potential role in patients in the early stages of aortic stenosis to slow the progression to severe aortic stenosis and to delay the timing of the need for surgery, but the mixed data from the trials likely relates to differences in the degree of LDL lowering and the initial valve area. Future studies are necessary for patients who have more mild aortic stenosis to determine the potential impact of statin therapy.
Co-authors: Nalini M. Rajamannan, MD, Patricia Best, MD, Francesco Antonini-Canterin, MD, Luis M. Moura, MD