In the absence of evidence that the cholesterol fighter Vytorin works better than a cheaper drug known as a statin, patients should turn back to using statins and other proven drugs, an expert panel said on Sunday.
The panel’s recommendations followed the presentation of a controversial study known as Enhance that found the combination drug made by Merck & Co and Schering-Plough Corp failed to show it worked any better than a cheaper generic statin in patients with an inherited form of heart disease.
Doctors had embraced the drug because it does such a great job of lowering low-density lipoprotein, or LDL, the so-called bad cholesterol.
“Our strongest recommendation is that people need to go back to statins,” said Dr. Harlan Krumholz of Yale University, who spoke on behalf of the panel at the American College of Cardiology meeting in Chicago.
Vytorin combines the statin Zocor, known generically as simvastatin, with another cholesterol medicine, Zetia or ezetimibe, and is marketed by a joint venture of Merck and Schering-Plough. Put together, Vytorin and Zetia have annual sales of about $5 billion.
Krumholz said the Enhance study’s findings should change the way cardiologists treat patients, switching patients to higher doses of statins and trying other proven drugs to reduce their cholesterol.
“We know statins are good drugs and we know they reduce risks. We believe in general to get to a $5 billion-a-year drug, there was a lot of premature use of ezetimibe before the statin option had been exhausted,” Krumholz told a media briefing after the panel.
The Enhance study shook many doctors’ assumptions about the notion that any means of lowering LDL would bring about benefits. Zetia and statins lower cholesterol in different ways, and some doctors at the meeting said the way you lower cholesterol may be important, too.
Panel member Dr. Rick Nishimura of the Mayo Clinic said the outcome of Enhance “reminds us to look at the trial endpoint and how (drugs) affect patients and not to just look at the numbers,” he said.
Several of the panelists said at the briefing that the results also call into question the use of so-called surrogate endpoints such as LDL, instead of a study with hard evidence that shows a drug helps patients, such as reducing heart attacks and strokes.
Krumholz also said the study makes it clear how little doctors know about the ezetimibe or even whether it is safe because the drug was approved without testing in a large group of patients over a long period to see if it raises heart attack and stroke risks.
“We do not know. This is a new drug with a novel mechanism- first in class. We do not have outcomes studies,” he said. Such a study, called Improve-It, is under way, but results won’t come until 2012.
Panelist Dr. Joseph Messer, a cardiologist from Chicago, said the panel’s recommendations reflect a consensus.
“We all believe in the LDL hypothesis and we all believe in the primary responsibility as a physician to do no harm,” he told reporters. “Since we do not know whether that harm could come from this drug, I think it is incumbent upon us to use it in a very conservative manner,” he said.
Schering-Plough strongly objected to the suggestion that the drug was harmful.
“We were very disappointed in the ACC panel. We had expected a balanced discussion and we really didn’t think the panel today served patients well,” Dr. Robert Spiegel, chief medical officer of Schering-Plough told Reuters.
“We were particularly concerned because we know of no safety concerns that should be raised after the Enhance trial. But we do know a lot about the value of LDL-lowering and that is what we had hoped the scientific discussion would address,” Spiegel said.
By Julie Steenhuysen