Rosuvastatin slows hemodynamic progression of aortic stenosis
Last Updated: 2007-01-29 17:00:09 -0400 (Reuters Health)
NEW YORK (Reuters Health) - The progression of asymptomatic aortic stenosis is slowed by treatment with rosuvastatin (Crestor), according to results of the RAAVE (Rosuvastatin Affecting Aortic Valve Endothelium) study, reported in the Journal of the American College of Cardiology for February 6th.
The risk factors for calcific aortic stenosis are similar to those for coronary heart disease, senior author Dr. Nalini M. Rajamannan and her associates note. For that reason, they hypothesized that statin treatment may slow aortic valve calcification.
Dr. Rajamannan, from Northwestern University Feinberg School of Medicine in Chicago, and her team conducted a prospective study with 121 patients to determine if rosuvastatin treatment affects the hemodynamic progression of moderate to severe aortic stenosis.
The subjects had asymptomatic aortic stenosis and an aortic valve area between 1.0 and 1.5 cm (normal aortic valve area = 3-4 cm). Sixty patients with LDL cholesterol less than 130 mg/dL received no statins, the authors report, while the 61 patients with higher LDL cholesterol levels were treated with rosuvastatin at 20 mg/day.
After a mean of 73 weeks, Dr. Rajamannan's group compared outcomes between groups. Adverse changes in hemodynamic markers - decrease in aortic valve area, increase in peak aortic valve velocity, peak gradient and mean gradient -- were significantly greater in the untreated group.
For example, aortic valve area decreased by 0.10 cm/year in untreated patients versus 0.05 cm/year (p = 0.041) in those treated with rosuvastatin; peak aortic valve velocity increased by 0.24 m/s/year versus 0.04 m/s/year, respectively (p = 0.007).
Several serum markers improved significantly only in the treated group - total cholesterol, LDL cholesterol, triglycerides, and high-sensitivity C reactive protein.
The research team suggests that in addition to their lipid-lowering effects, statins affect aortic stenosis by inhibiting cellular proliferation. Statins also reduce activation of the osteogenic gene program in the aortic valve myofibroblast and modulate endothelial nitric oxide synthase to improve endothelial function.
In an accompanying editorial, Dr. Brian P. Griffin, from Cleveland Clinic in Ohio, points out that the result of the similar SALTIRE study indicated that statin therapy was of no benefit to patients with aortic stenosis and hyperlipidemia.
However, he adds that patients in the SALTIRE study had more advanced aortic stenosis and a greater degree of valve calcification than did those in the RAAVE study.
Dr. Griffin, as well as the RAAVE researchers, agree that more severe aortic stenosis probably does not respond to statin treatment. But for those with less advanced, asymptomatic aortic stenosis, Dr. Rajamannan's group concludes that "targeting this disease with medical therapy may be an important therapeutic strategy in the future."
J Am Coll Cardiol 2007;49:554-564.
