New research into a possible link between a cholesterol-reducing drug and cancer concluded there was no proof to establish a connection, but other doctors warned that it should be used more carefully.
In a paper published Tuesday by the New England Journal of Medicine, Terje Pedersen and colleagues found that cancer occurred more frequently in patients taking Vytorin, a combination of Merck's Zocor and Schering-Plough's Zetia, than in people on a placebo pill. But that study was too small to stand as proof of a real link.
In a larger analysis of data considering the possible link between Vytorin and cancer, also published in the New England Journal of Medicine, epidemiologists said there was no evidence implicating Vytorin, which millions of people take worldwide.
The two papers were also presented at a meeting of the European Society of Cardiology in Munich.
But not all doctors were convinced that Vytorin is risk-free.
"I think the jury is still out as to whether there's a cancer signal," said Dr. Gordon Tomaselli, chief of cardiology at Johns Hopkins Hospital, and spokesman for the American Heart Association. Tomaselli was not connected to the research.
The trial's preliminary results were announced ahead of schedule in July, when investigators discovered a higher incidence of cancer in patients on Vytorin.
At that point, Sir Richard Peto, a cancer epidemiologist, rushed to crunch numbers from Pedersen's study with two bigger Vytorin studies to see if the drug might be linked to cancer.
"I don't think there is any evidence of hazard here," Peto said. Peto's group at Oxford University is carrying out another trial on Vytorin funded by Merck & Co. and Schering-Plough Corp. They found that there was a lower incidence of cancer among people on Vytorin, but that the death rate was higher.
Pedersen's original trial aimed to determine whether Vytorin might help prevent problems with the heart valve. Vytorin lowers cholesterol, which doctors thought might also help reduce the risk of heart valve problems, which affect millions of people worldwide.
Problems occur when the valve becomes blocked or stiff, compromising its ability to pump oxygen-rich blood throughout the body.
In the trial, Vytorin was no better at reducing the risk of heart problems than were the fake pills people took.
They followed 1,873 patients in Europe and the United States. Patients were either given Vytorin or a placebo. Of patients on Vytorin, 105 developed cancer, compared with 70 among those on placebo.
Some doctors suggested that the hypothesis behind the trial was mistaken, and that heart valve problems can only be solved with surgery, not with medication.
But they said the drug is still useful for people who need their cholesterol lowered — if other drugs do not work.
"If I was on this medication and it was the only way to get my cholesterol down, I would not change my therapy based on this," said Dr. Douglas Weaver, president of the American College of Cardiology. The College has been asked by the U.S. Senate to account for the money it accepts from pharmaceutical companies, including Merck.
The New England Journal of Medicine editors had a staff statistician look at combined cancer deaths from all three Vytorin studies. They say the extra risk "should not be assumed to be a chance finding" until more information is in. Doctors and patients now are left with "uncertainty" about the safety and effectiveness of the drug, the journal's editors concluded.
With other options available for heart patients, some doctors said there was no obvious reason to take Vytorin. "There's no proof that this combination is working," said Dr. Christer Hoglund, a cardiologist at Sweden's Karolinska Institute.
"We don't know that this drug is bad, but we don't know that it's any good either."