FDA unable to rule out vytorin-cancer link

By Jimmy Downs

The Food and Drug Administration in Aug 21, 2008 issued a statement saying that it had informed health professionals of a link between use of a combination of Simvastatin and Ezetimibe or simply vytorin and increased risk of a variety of cancers in the Aortic Stenosis (SEAS) trial.

Vytorin is an experimental drug indicated to lower cholesterol.  And the drug makers Merck and Schering-Plough Pharmaceuticals are hoping that the combo may reduce cardiovascular adverse events in patients with aortic stenosis.

AT the time the FDA learned of the vytorin-cancer link, the trial had not been complete yet even though part of the 5-year study had indicated the drug did not reduce cardiovascular risk and a higher percentage of patients receiving the drug were diagnosed with and died from a variety of cancers compared to those treated with a placebo, according to the FDA statement.

On Dec 22, 2009, the FDA again posted a statement on its website that it is unlikely that vytorin, the cholesterol lowering drug, causes cancer; but the association cannot be ruled out.

According to the FDA, the SEAs trial involved 1,873 patients with aortic stenosis - a condition in which patients have narrowed aorta, the main blood vessel leaving the heart. 

In the trial, patients were given a combo of 10 mg ezetimibe and 40 mg simvastatin or a placebo for four years to determine if lowering LDL-cholesterol lowering with vytorin would reduce the number of major cardiovascular adverse events.

The vytorin did not result in a lower overall cardiovascular risk, the FDA cited the trial report as saying.

On the other hand, the agency revealed that "During the trial, investigators reported an increased number of cancers and cancer-related deaths in patients using Vytorin compared to placebo. Cancer was reported in 105 patients (11.1%) in the Vytorin group and in 70 patients (7.5%) in the placebo group. The number of deaths from cancer was also higher in the Vytorin group, with 39 deaths compared to 23 deaths in the placebo group."

Another trial called SHARP using a lower dose of vytorin, to be extract, a combo of 20 mg of simvastatin and 10 mg of ezetimibe and another trial known as IMPROVE-IT which compared vytorin in a dose used in SEAS did not show an increased risk of developing cancer associated with the weak version of vytorin.

This finding may give the public an impression that the dose may make a difference.  Is it possible that researchers did not find a link between vytorin use and increased cancer risk because the SHARP trial used a lower dose of simvastatin?

There is a statistically insignificant association between use of the weak vytorin and cancer deaths.  

"There was an increase in the number of cancer-related deaths, with 97 deaths in the Vytorin groups compared to 72 deaths in the control groups, but this finding was not statistically significant," the FDA states.

Both SHARP and IMPROVE-IT are ongoing and will be completed in 2010 and 2012, respectively.

The FDA listed quite a few findings from various sources to justify its assertion that it is unlikely that vytorin causes cancer. One reason is that "Preclinical (animal) studies did not find that ezetimibe was associated with an increased incidence of cancer."

The food and drug agency did not elaborate the conditions in which the animal studies were conducted.