FDA Investigates Possible Vytorin-Cancer Link

THURSDAY Aug. 21, 2008 -- U.S. drug regulators said Thursday that they were investigating whether the cholesterol-lowering drug Vytorin might be linked to cancer.

The U.S. Food and Drug Administration said it has informed health-care professionals that the agency was investigating a report from the so-called Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) trial of a possible association between the use of Vytorin and an increased risk of a variety of cancers.

Vytorin is a combination drug made up of the compounds simvastatin and ezetimibe that's designed to reduce levels of LDL (bad) cholesterol and cut the risk of cardiovascular problems. It works by decreasing the production of cholesterol by the liver and inhibiting the absorption of cholesterol in the intestine.

In a statement released Thursday afternoon, the FDA said it had obtained preliminary results from the SEAS trial. The trial tested whether lowering LDL-cholesterol with Vytorin would reduce the risk of cardiovascular problems in people with narrowing of the aorta, the body's largest artery. The five-year trial did not show a reduced cardiovascular risk. But, a "larger percentage of patients treated with Vytorin were diagnosed with and died from all types of cancer combined, when compared to treatment with a placebo," the statement said.

However, the FDA said patients can continue to take the drug. But the agency urged health-care professionals to monitor their patients for possible side effects and report them to the agency. While one recent clinical trial indicated higher rates of cancer for patients taking the drug, the FDA said two studies currently under way have shown no increased risk, the Associated Press reported.

The agency said it expects to receive a final study from the SEAS trial in about three months. It will then take an estimated six months to review and evaluate the trial data.

Vytorin is made by the drug companies Merck & Co. and Schering-Plough Pharmaceuticals. It's a combination of Merck's Zocor (simvastatin), a statin, and Schering-Plough's Zetia. A report earlier this year found the drug failed to reduce the buildup of plague in arteries any better than the generic drug Zocor.

Following the FDA's announcement Thursday about the possible Vytorin-cancer link, several Congressional lawmakers issued a demand for data on the trial that suggested a potential connection, the AP said.

Merck and Schering-Plough said they would cooperate with the requests. The companies defended the drug, saying it is effective at reducing cholesterol -- the use for which it was approved, the AP reported.

Earlier this week, researchers who last year reported a possible link between cholesterol-lowering statin drugs and cancer now say that further analysis has disproved such an association.

"The bottom line is that there is no evidence from this work, the largest study published to date, that the cholesterol-lowering ability of statins increases the risk of cancer," said Dr. Richard H. Karas, director of preventive cardiology at Tufts Medical Center and leader of a group reporting the finding in the Journal of the American College of Cardiology.

A little more than a year ago, a report by Karas and his colleagues in the same journal described a slight increase in cancer risk among statin users -- about one extra case per 1,000 people. That finding came from 13 trials that gathered information on side effects reported by people who took the drugs.

The newer report had data from 15 controlled trials involving more than 437,000 person-years of follow-up. The analysis did find a relationship between low levels of LDL cholesterol -- the "bad" kind that clogs arteries and that statins attack -- and a higher incidence of cancer. However, the team concluded that statins, per se, "lack an effect on cancer risk across all levels of on-treatment LDL cholesterol."

An even larger study by Sir Richard Peto, the renowned British epidemiologist, reported at a meeting but not yet published in a medical journal, came to the same conclusion, Karas said.

An association between low levels of LDL cholesterol and cancer is no surprise, said Dr. Daniel Steinberg, professor emeritus of medicine at the University of California, San Diego. He wrote an editorial accompanying the report.

"The so-called J-shaped curve has been seen repeatedly when cholesterol has been measured," Steinberg said. "In such studies, persons with the lowest LDL cholesterol on entry show the highest death rate from cancer than those with higher LDL levels."

One possible mechanism is that cancer itself reduces LDL cholesterol levels, he said. "This is especially true of cancers involving the blood cell system, but it also occurs with cancer of the kidney and elsewhere," Steinberg said.

"Whatever the mechanism, the main point should be that studies of much larger numbers of people in statin trials find no excess of cancers," he said.

More information

There's more on statins at the American Heart Association.

Posted: August 2008


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