New Vytorin heart study ushers in more bad news for Merck, Schering

The SEAS study found that Merck/Schering-Plough’s Vytorin, in patients with mild to moderate aortic stenosis reduces the risk of coronary artery disease events, but not the rate of progression of aortic valve disease. The study also found slightly higher rates of cancer with the Vytorin arm.

The SEAS (Simvastatin and Ezetimibe in Aortic Stenosis) study is the first large-scale, randomized trial to assess the effects of lowering LDL-cholesterol in patients with aortic stenosis.

The study was initiated and designed by academic researchers in Scandinavia, and carried out at 173 clinical centres in Norway, Denmark, Sweden, Finland, Germany, U.K. and Ireland. It 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, according to researchers.

The investigators observed no significant difference between Vytorin (simvastatin/ezetimibe) and placebo in the study which was designed to determine whether the drug can lessen the need for surgical replacement of aortic valves, reduce cardiac death and events, including heart attacks.

Vytorin cut cholesterol levels by 61 percent compared with a placebo. Still, 333 patients getting the drug suffered a complication, compared with 355 on placebo, almost identical rates, the study found.

The investigators reported that a combination of simvastatin and ezetimibe did produce a statistically significant 22 percent proportional reduction in the secondary endpoint of atherosclerotic events alone: 148 (15.7 percent) in the simvastatin plus ezetimibe group versus 187 (20.1 percent) in the placebo group.

The SEAS researchers also found that 158 patients developed cancer–9.9 percent of which were receiving Vytorin and 7 percent of which were receiving placebo. Deaths from cancer were also slightly higher in those given Vytorin (4.1 vs. 2.5 percent), the study found. The “apparent differences were not related to any particular type of cancer and did not become significantly larger with more prolonged treatment,” the researchers wrote.

The investigators also noted that the SHARP and IMPROVE-IT studies involve about four times as many cancers as in the SEAS study; and the analysis of SHARP and IMPROVE-IT did not support the suggestion of an increase in cancer that was raised by the subsidiary analyses of the relatively small numbers of cancers in the SEAS study.

The first patient was enrolled in 2001, and completed when the last patient had been followed for four years in March.

The SEAS study was funded by the pharmaceutical companies Merck Sharp & Dohme and Schering-Plough who market the drugs being tested.

Bloomberg reported that Vytorin prescriptions have dropped by about a third since January when an ENCHANCE found it worked no better than Zocor alone in reducing plaque buildup in the heart’s main artery. The newest study, originally slated for presentation at a medical meeting in November, looked at narrowing of the heart's aortic valve, in patients on Vytorin.