A clinical trial of a widely used cholesterol drug has raised questions both about the medicine’s effectiveness and about the behavior of the pharmaceutical companies that conducted the study, cardiologists said Monday.
Merck and Schering-Plough, which make the drug, Zetia, and a pill that contains it, Vytorin, said Monday morning that Zetia had failed to benefit patients in a two-year trial that ended in April 2006.
Merck and Schering repeatedly missed their own deadlines for reporting the results, leading cardiologists around the world to wonder what the study would show. At the same time, millions of patients have continued taking Zetia and Vytorin.
The drug companies blamed the complexity of the data for the delay. Now, barely a month after news articles noted the delay and Congress pressured the companies to disclose the study’s findings, the results are out.
In a press release, Merck and Schering said that not only did Zetia fail to slow the accumulation of fatty plaque in the arteries, it actually seemed to contribute to plaque formation — although by such a small amount that the finding could have been a result of chance.
Dr. Steven E. Nissen, the chairman of cardiology at the Cleveland Clinic, said the results were “shocking.”
“This is as bad a result for the drug as anybody could have feared,” said Dr. Nissen, a widely published researcher and senior consulting editor to the Journal of the American College of Cardiology. Millions of patients may be taking a drug that does not benefit them, raising their risk of heart attacks and exposing them to potential side effects, he said. Patients should not be given prescriptions for Zetia unless all other cholesterol drugs have failed, he said.
Both companies’ shares fell Monday. Sales of the two drugs were $5 billion in 2007, and they are important contributors to Merck’s and Schering’s profits.
The House Energy and Commerce Committee, which is investigating the delay, said in a statement Monday that the negative results added to suspicions that the companies had deliberately sat on their findings from the study, which was known as Enhance.
“In light of today’s results, which were released nearly two years after the Enhance trial ended, it is easy to conclude that Merck and Schering-Plough intentionally sought to delay the release of this data,” Representative Bart Stupak, Democrat of Michigan, said in the statement. Mr. Stupak is chairman of the committee’s Subcommittee on Oversight and Investigations.
Dr. Harlan M. Krumholz, a cardiologist at Yale, said drug companies had a responsibility to release all their trial findings, positive or negative, as quickly as possible — even if the results might hurt sales.
“People may have been on this drug without the ability to know that there was additional data that may have thrown into question its effectiveness,” Dr. Krumholz said. “That’s extremely unfortunate, and that’s an understatement.”
Lee Davies, a spokesman for Schering, said the delay was unrelated to the negative findings and that the companies had not known the results until two weeks ago.
Dr. John Kastelein, a Dutch cardiologist who had conducted the Enhance trial for Merck and Schering, did not return calls or reply to an e-mail message seeking comment. Mr. Davies said that Dr. Kastelein would not comment until he formally presented the results at a cardiology conference in March.
In the trial, patients received either Zocor — an older cholesterol drug — or a combination of Zocor and Zetia, in the pill form known as Vytorin. About 60 percent of patients who take Zetia do so in the Vytorin form, which like Zetia is jointly marketed by Merck and Schering.
Worldwide, about one million prescriptions are written for Zetia and Vytorin each week, and about five million people are now taking the drugs worldwide.
The trial covered 720 patients and lasted two years. While it was relatively small, cardiologists have been eager to see its results because they have far less data on Zetia than on other cholesterol-lowering medicines.
