Santé Magazine
Salute Magazine
Новости Здоровья
On Sunday, March 30, a panel of four cardiologists voiced their recommendations for using the controversial cholesterol drug Vytorin. The drug, a joint venture between drug makers Merck and Schering-Plough, combines the active ingredients of Zocor (simvastatin) with Zetia (ezetimibe) into a single pill. Zocor is a statin, which blocks the liver from making cholesterol, while Zetia works by blocking the intestine from absorbing cholesterol in food.
The panel, comprised of Dr. Harlan M. Krumholz (Yale), Rick Nishimura (Mayo Clinic), Patric O'Gara (Brigham and Women’s Hospital), and Joseph Messer (private practice), spoke to approximately 5,000 attendees of the annual meeting of the American College of Cardiologists. The topic was the full study results of a two-year clinical trial, known as Enhance, first summarized in a press release issued on January 14. The study, which involved 720 patients with a family history of unusually high cholesterol, revealed that higher-priced Vytorin fared no better than the less expensive Zocor. Despite reducing cholesterol levels, Vytorin failed to slow, and may have even sped up, the accumulation of fatty deposits in arteries, which is closely correlated with heart attacks and stroke.
LDL or “bad” cholesterol is known as a risk factor for heart disease. It has been the general consensus among doctors that lowering LDL cholesterol would reduce the risk of heart attacks and strokes. However, proving that a drug actually cuts those risks requires what is known as “outcomes trials,” which are multiyear studies involving at least 10,000 patients. Statins such as Lipitor and Zocor have been proven in outcomes trials to reduce the risk of heart disease. But no outcomes trials exist for Vytorin and Zetia.
As a result, doctors prescribing the medicines are doing so without hard evidence that they help patients, said Dr. Steven Nissen, chairman of cardiology at the Cleveland Clinic. “We’ve got a drug that has no clinical outcome trials. I advise my colleagues essentially to use this drug only as a last resort.”
The opinions from the panel, based on the Enhance trial were, not in favor of prescribing Vytorin in the majority of cases. While endorsing it as a strong study, the panel strongly recommended that people need to go back to statins, with Dr. Krumholz further stating that, “We really think there’s just a small group of patients who cannot get to target cholesterol on statins.” He recommended that doctors maximize the doses of statins and then try adding other drugs such as niacin or fibrates in an attempt to lower LDL cholesterol levels. Statins include drugs like Lipitor and simvastatin, the generic version of Zocor. They have proven benefits and can be cheaper, the panel said.
The New England Journal of Medicine also published the study online along with two editorials which made recommendations similar to those made by the panel. One of the journal papers was co-authored by Dr. Krumholz, in which he recalled the history of torcetrapib, a drug developed by Pfizer that increased blood levels of HDL cholesterol, the “good” kind that prevents plaque formation. Tests of the drug were stopped in 2006 because the trial showed higher mortality rates among those taking it. “It was a new drug, the first in its class,” Dr. Krumholz said. “The laboratory results looked great, and it ended up hurting people.”
Dr. Krumholz said it’s not clear whether the same will be true of Vytorin. “The evidence we have on hand makes a benefit less likely,” he said. “We have a $5-billion-a-year market without outcomes data.”
At a press conference later in the day, chief medical officer and senior vice president at Schering-Plough, Robert J. Spiegel, M.D., said that the drug makers were “very disappointed in the ACC plenary presentation. We had expected a scientific panel discussion and the discussion we got did not serve science well.” Dr. Spiegel also said that he was particularly disturbed by Dr. Krumholz’ comparison of ezetimibe to torcetrapib saying, “There is absolutely no safety signal with our drug. We have over 10 million patient-years with this drug and no new safety issue has arisen. So we are very disturbed that this issue was raised. It does not come from data that we have tracked for the FDA.”
Dr. Douglas Weaver, the incoming president of the American College of Cardiology (ACC), says the recommendations released Sunday will probably have an immediate impact on clinical practice. The ACC was the host of the conference, which was attended by nearly half of the 30,000 cardiologists in the United States, many of which heard the recommendations firsthand.
“I do think that the drugs have been over utilized in this country,” said Dr. Weaver, who also added that the overuse was due, in part, to heavy marketing. As more doctors and patients focus on the results of the Enhance trial, use will decline. “Sometimes you have to tell people multiple times before they get the message,” he said.
Vytorin and Zetia are among the top selling drugs in the world, with about 5 million people worldwide taking the medicines. Four million of those users are Americans.
