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Title: Simvastatin-Ezetimibe Combination Does Not Slow Progression of Aortic Valve Disease

"Simvastatin-Ezetimibe Combination Does Not Slow Progression of Aortic Valve Disease"

NEW YORK -- July 21, 2008 -- The combination of simvastatin and ezetimibe in patients with mild to moderate aortic stenosis appears to reduce the risk of coronary artery disease (CAD) events but not the rate of progression of aortic valve disease. The Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study was a large-scale randomised trial to assess the effects of lowering low-density lipoprotein (LDL) cholesterol in patients with aortic stenosis. The study was initiated and designed by academic researchers in Scandinavia and was conducted at 173 clinical centres in Norway, Denmark, Sweden, Finland, Germany, United Kingdom, and Ireland. The study included 1,873 patients with mild to moderate aortic stenosis without symptoms who were not considered to have a clear indication for treatment with cholesterol-lowering drugs. Patients were randomly assigned to receive either simvastatin 40 mg QD and ezetimibe 10 mg QD or matching placebo. The first patient was included in 2001, and the study was completed when the last patient included had been followed for 4 years (March 2008). The primary endpoint of the SEAS study was major cardiovascular events. The secondary endpoints were aortic valve disease events and atherosclerotic disease events. Subsidiary outcomes included echocardiographic evidence of aortic stenosis progression and safety. Compared with placebo, the combination of simvastatin and ezetimibe reduced LDL cholesterol by an average of 61%, corresponding to a reduction of about 2 mmol/L (76 mg/dL), and this effect was sustained throughout the study. Of the patients, 688 had 1 or more primary endpoint events. No significant difference was observed between the treatment groups for the combined primary endpoint (333 patients with an event on LDL-lowering treatment vs 355 on placebo; hazard ratio (HR) = 0.96; 95% confidence interval (CI) 0.83-1.12). There was also no significant difference for the secondary endpoint of aortic valve disease events alone (308 vs 326; HR, 0.97; 95% CI, 0.83-1.14). The combination of simvastatin and ezetimibe did, however, produce a 22% reduction in the secondary endpoint of atherosclerotic events alone (148 vs 187; 95% CI, 3% to 37%; [P = .02).

The study therapy was generally well tolerated, with no significant differences between the treatment groups in the proportion of patients who stopped taking the study treatment. In the subsidiary safety analyses, a total of 158 patients were recorded with a serious adverse event attributed to cancer.

More adverse events were observed among patients assigned to simvastatin and ezetimibe (9.9%) compared with patients assigned to placebo (7.0%), including slightly more cancer deaths (4.1% vs 2.5%). These apparent differences were not related to any particular type of cancer and did not become significantly larger with more prolonged treatment.

In conclusion, the SEAS study has found that intensive LDL-cholesterol lowering with the combination of simvastatin and ezetimibe in patients with mild to moderate aortic stenosis does appear to reduce the risk of CAD events (as has been shown for many other types of patients in previous trials) but not the rate of progression of aortic valve disease.

SOURCE: CNW Group Ltd

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