Vytorin Comes Under Fire Yet Again

It was one step forward and one step back for Merck and Schering-Plough's beleaguered cholesterol drug Vytorin, as the New England Journal of Medicine published an analysis suggesting that recent reports of increased cancer risk with the drug were probably a statistical anomaly—then editorialized that patients and physicians should still be cautious.

Presented at the European Society of Cardiologist's meeting on Tuesday (and originally released in July), the SEAS (Simvastatin and Ezetimibe in Aortic Stenosis) study was performed to determine whether Vytorin could be used to treat aortic stenosis or partial blockage in the heart's aortic valve. (Statins have had a mixed record with heart valve disease.) A group of 1,873 patients were given either intensive cholesterol lowering treatment with the combination of simvastatin and ezetimibe, or they were given a placebo for four years.

The data showed that the combination drug reduced LDL-cholesterol by an average of 61 percent (thereby reducing the risk of coronary artery disease events), but didn't do much to reduce aortic valve disease events.

What caused a ruckus was the spike in cancer for patients taking the combination treatment. Of the 175 patients who had a serious adverse event attributed to cancer, 105 of them were taking the medication versus 70 on the placebo. However, the study investigators said that it could have been a fluke.

"The observed differences in cancer in the SEAS study are based on small numbers, and could have occurred as a result of chance," stated lead investigator Terje R. Pederson in a presentation. To assess the data, the SEAS data were given to the Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU) of Oxford University, an independent academic group. The group was also provided with unblended data from two ongoing Vytorin studies, IMPROVE-IT and SHARP, which included a total of more than 20,000 patients.

The group's analysis confirmed that Vytorin did not cause additional cancer cases, and that there were no significant trends in regard to location of the cancer or timing of onset. But when investigators looked at deaths by cancer, the Vyrotin group had a slightly higher (and statistically insignificant) number of deaths: 97, versus 72 in the control groups (P=0.07).

And that, argues the journal in an editorial, means there is still cause for concern.

"The fact that the combined data from all three trials showed an increase in cancer mortality with ezetimibe should not be assumed to be a chance finding until further data are in," the New England Journal stated.

Some commotion has been made over whether or not Merck and Schering-Plough jumped the gun by releasing the data too soon. But the companies wanted to avoid the problems they had with the ENHANCE trial earlier this year, which stemmed partially from a delay in releasing results. A spokesperson told the Wall Street Journal they "wanted to inform regulatory agencies worldwide and to make the disclosure to investors. The criticism about the early timing makes us feel like we're damned if we do and we're damned if we don't."