The Food and Drug Administration (FDA) has concluded that, at this time, there's no evidence that the combination lipid-lowering drug Vytorin (the cholesterol-lowering statin simvastatin plus the cholesterol absorption inhibitor ezetimibe) increases the risk of cancer or cancer-related death.

The FDA had issued a warning in August of last year that the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) trial had revealed a greater incidence of cancer in the treatment group than in the placebo group. Its most recent announcement comes on the heels of a follow-up analysis showing that the higher rate in the treatment group was likely the result of all cancers having been combined for analysis. "It is biologically less likely that a single drug increases the risk of a wide variety of cancer types," wrote the FDA (http://bit.ly/4uA1XC), which concluded that neither the combination drug nor ezetimibe (Zetia) alone increases cancer risk. Because the SEAS trial wasn't designed to look at cancer risk, the analysis "was performed after the fact and without statistical correction to account for multiple comparisons. Therefore, the true statistical significance of the cancer imbalance is unknown," said the FDA.

Further bolstering the FDA's conclusion are interim data from two ongoing, large-scale clinical trials involving the combination of simvastatin and ezetimibe, the Study of Heart and Renal Protection (SHARP) and the IMProved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT), although results from IMPROVE-IT, which isn't due to conclude until 2012, could ultimately shed more light on any association between use of the combination drug and cancer.

In March 2008 preliminary results of the Ezetimibe and Simvastatin in Hypercholesterolemia Enhances Atherosclerosis Regression (ENHANCE) trial showed the combination drug to be no more effective than simvastatin alone in reducing carotid artery-plaque formation (see Drug Watch, May 2009). Because the two ongoing trials are much larger than the ENHANCE trial, the FDA doesn't recommend any changes in use of the drugs at this time. Nurses should tell patients to continue using their prescribed cholesterol-lowering drugs. Nurses should also be alert to any changes in FDA guidance as the data from SHARP and especially IMPROVE-IT become known.