New trial spells more trouble for Vytorin

LONDON In a clinical trial called Seas, Merck and Schering-Plough’s cholesterol drug Vytorin did not help people with heart-valve disease avoid further heart problems but did appear to increase their risk of cancer, according to published reports.

The scientists who reported on the trial cautioned against worrying over the cancer findings, saying that even well-designed clinical trials sometimes produce chance results. A review of two other, much larger trials did not find a similar risk, they said. But other cardiologists and epidemiologists said that the cancer risk could not be so easily dismissed.

The findings of the Seas trial will heighten concerns about Vytorin’s safety and effectiveness, said Steven Nissen, a former president of the American College of Cardiology and a longtime critic of Vytorin. Six months ago, a fourth clinical trial, called Enhance, also failed to show that the drug benefited patients, leading a panel of top cardiologists to recommend using Vytorin and one of its ingredients, Zetia only as a last resort.

In the Seas trial, which involved nearly 1,900 patients whose heart valves were partially blocked, participants were given either Vytorin or a placebo pill. Scientists had hoped that the trial would show that patients taking Vytorin would have a lower risk of needing valve replacement surgery or having heart failure. But the drug did not show those benefits.

However, patients taking Vytorin in the Seas trial did have a sharply higher risk of developing and dying from cancer. In the trial 102 patients taking Vytorin developed cancer, compared with 67 taking the placebo. Of those, 39 people taking Vytorin died from their cancer, compared with 23 taking placebo.

To evaluate the cancer findings, Richard Peto, professor of medical statistics and epidemiology at the University of Oxford, examined the interim results of two other clinical trials of Vytorin—called Sharp and Improve-It. The University of Oxford is leading the Sharp trial, which is sponsored by Merck and Schering-Plough but run independently by the university’s Clinical Trial Service Unit. Investigators by Harvard and Duke University are leading the Improve-It trial. Both Sharp and Improve-It are comparing Vytorin with Zocor alone.

Neither trial has been completed yet, but the two trials combined have about 20,000 patients, nearly 10 times as many as the Seas trial.

So far, about the same number of patients taking Vytorin in Sharp and Improve-It have developed cancer as those taking Zocor alone, Peto said on Monday. That fact strongly suggests that the finding in Seas is due to chance, Peto said.