Merck & Co and Schering-Plough have been hurt again by the release of new data which shows that their cholesterol drug Vytorin failed to meet its primary goal of improving cardiovascular outcomes for patients with aortic stenosis compared to placebo.

The highly-anticipated data comes from the SEAS study which involved 1,873 patients with mild-to-moderate aortic stenosis, which involves partial blockage of the aortic valve in the heart. No significant difference was observed between Vytorin (ezetimibe/simvastatin) 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.

The data also showed that there was no significant difference between treatment groups for the secondary endpoint of aortic valve disease events alone, although patients who received Vytorin did have a statistically significant 22% reduction in atherosclerotic events alone, compared with placebo. Nevertheless, the study has given “a clear-cut answer whether lipid lowering will influence the cause of aortic stenosis” and we can conclude it does not," said principal investigator Terje Pedersen of Ulleval University Hospital in Oslo, Norway.

Another element that raised eyebrows about the study involved data which demonstrated that 39 patients who took Vytorin died of cancer, compared with 23 in the placebo group. However the researchers noted that “the observed differences in cancer in the SEAS study are based on small numbers and could have occurred as a result of chance”.

Furthermore, an independent analysis by the University of Oxford Clinical Trial Service Unit and Epidemiological Studies Unit proposed that the hypothesis-generating results of the SEAS trial of ezetimibe should be tested by reviewing the combined cancer results from two other trials of ezetimibe, SHARP and IMPROVE-IT.

The latter two studies contain about four times as many cancers as the SEAS trial but they do not confirm the hypothesis raised by the latter that treatment increases the overall risk of developing cancer. The independent observers added that the SEAS, SHARP and IMPROVE-IT trials “do not provide credible evidence of any adverse effect on cancer”.