MOUNT VERNON — The results of a recent study named ENHANCE, a clinical trial of the statin (cholesterol-lowering) drug Vytorin, a combination of Zetia (ezetamide) and Zocor (simvastatin), is causing concern in patients and in the medical community.
Zetia and Vytorin are manufactured by the drug companies Merck and Schering-Plough, which sponsored the two-year study. Taken by millions of patients, the statin drugs generated sales of more than $5 billion in 2007. That may explain why the companies did not release the results for more than a year, and then only after pressure from Congress and media outlets. According to the New York Times, a U.S. House of Representatives investigation will take place.
Patients in the trial received either Zocor or Vytorin, and the results showed that Vytorin reduced LDL, bad cholesterol, levels better than Zocor alone, but did not reduce the formation of fatty artery plaque. The news alarmed patients and surprised doctors.
But there is criticism of the study.
The 720 European participants in the trial suffered from a rare genetic abnormality — Heterozygous Familial Hypercholesterolemia — that causes abnormally high LDL cholesterol levels of 318 and higher, three times the average — that puts them at high risk of heart attacks and strokes.
“That is much, much higher than what we see in the average patient,” said J. Pala, M.D., medical director of cardiology at Knox Community Hospital and Knox Cardiology Associates Inc. “In Knox County, it would be very rare for even a handful of people to have this.
“The study is not definitive because it’s only one study. It was not a clinical outcome study. It was an imaging study that measured the thickness of the carotid artery intima, using ultrasound. It did not show that Vytorin made a difference, but other studies are still being done and I need to review those before I make a decision about Vytorin.”
The manufacturers are conducting three larger trials but the results will not be available until 2011.
“I’m going to wait and see,” said Robert Rodstrom, M.D., of Mount Vernon, “until the final presentation in March at the American College of Cardiology conference, where the trial will be summarized in more detail.”
The college issued a statement “recommending that major clinical decisions not be made on the basis of the ENHANCE trial,” said Thomas Dayspring, M.D., of New Jersey. He added, “There’s no reason for patients to panic. Patients should not stop their medication. Zetia remains a reasonable option.”
The National Lipid Association also released a statement.
“The limitations of the ENHANCE study, in terms of its design and the patients studied, are such that physicians should not alter their prescribing policies at this time,” the statement read. “Current discussion regarding the ... study is not based upon published work subject to peer review and thus cannot yet be evaluated by the medical community. Given that other studies are currently in progress to examine cardiovascular endpoints, generalization and extrapolation of ENHANCE results to different populations with regard to clinical outcomes is premature.”
Randy Orsborn, P.A., also of Knox Cardiology, said their office received numerous calls from concerned patients.
“One study doesn't make a drug good or bad,” said Orsborn, “but people tend to over-react to one situation. We’ve been through this before, with other products. The drug is perfectly safe. It just didn’t help as it was predicted it would in this one setting. Vytorin is ... a reasonable option for patients who cannot tolerate statin drugs or can only tolerate a low dose of a statin.
“One has to be careful what one reads,” said Orsborn. “Our patients do great on this drug and it is safe. What they don’t tell you is all of the other health issues the patients in the study have or had. They had LDL levels higher than 300 ... that’s relatively unheard of in the normal population.”
Rodstrom said he prescribes other statin drugs, such as Zocor and Lipitor, which have proven to be beneficial.
“I’m going to use caution,” he said. “I think I would not start new patients [on Vytorin] for now. I’ll review the information, review the indications for each patient who is on it, and do periodical tests.”
“I will reserve its use only for certain groups of [high risk] people,” said Pala. “We know that statins reduce heart attacks, reduce strokes and save lives. The most important thing to me as a physician is does Vytorin reduce heart attacks and strokes more than statin drugs alone? That question remains unanswered.
“There should not be an overreaction to this, based on one clinical study,” said Pala.
