No link found between ezetimibe and cancer incidence in meta-analysis

Data from three trials are insufficient to conclude that ezetimibe causes adverse effects on rates of cancer, according to researchers from Oxford University in the United Kingdom and Duke Clinical Research Institute at Duke University in North Carolina.

In August the FDA warned of a potential link between simvastatin plus ezetimibe based on data from the SEAS trial. The researchers conducted a meta-analysis comparing the incidence of cancer from the SEAS trial with an analysis of cancer data from the SHARP and IMPROVE-IT trials. All three trials examined the efficacy of ezetimibe plus simvastatin. The SEAS trial included 1,873 patients, the SHARP trial included 9,264 and the IMPROVE-IT trial included 11,353 patients.

Ezetimibe was associated with an increase in any new onset of cancer from several sites in the SEAS trial (101 patients in the active-treatment group vs. 65 controls). According to the researchers, no excess of cancer and no excess at a particular site were found in the SHARP and IMPROVE-IT trials combined (313 active-treatment vs. 326 controls; RR=0.96; P=.61).

Though most deaths from cancer occurred among patients assigned to ezetimibe, the number of excess deaths was not significant (97 active-treatment vs. 72 controls; P=.07). However, there were fewer cases of cancer, though the number of fewer cancers was not significant (216 active-treatment vs. 254 controls; P=.08).

“There was no evidence of a trend in the RR for incidence of or death from cancer with increasing duration of follow-up,” the researchers wrote.

Based on their findings, the researchers concluded that studies with longer follow-up are needed to better determine the balance of risks and benefits.

N Engl J Med. 2008;359:1357-1366.