Pfizer Releases Statement on Cardiovascular Safety of Celecoxib (Celebrex)
On December 17, 2004, Pfizer Inc released new information regarding the cardiovascular safety of celecoxib based on interim analyses of results from two long-term cancer trials, the Adenoma Prevention with Celecoxib (APC) trail and the Prevention of Spontaneous Adenomatous Polyps (PreSAP) trial. Interim review by the APC trials independent Data Safety and Monitoring Board (DSMB) of patients completing two years of therapy with celecoxib (combined 400mg and 800 mg per day groups) revealed an approximately 2.5 fold increase in major fatal and non-fatal cardiovascular events compared to patients receiving placebo. Based on this review, dosing of celecoxib was halted for this trial. An identical review by the same DSMB of the interim data from the PreSAP trial showed no increase in cardiovascular events among patients completing two years of therapy with celecoxib (400 mg per day only). Celecoxib dosing continues for this trial. Approximately 2,400 subjects were evaluated in these interim analyses. Other details about characteristics of the study participants (age, cardiovascular risk factors, concomitant aspirin use, etc) were not included in the release. A recent interim analysis by the DSMB of a third study of patients at high-risk for Alzheimers disease, including 750 subjects receiving celecoxib at a dose of 400 mg per day, did not result in recommendations to alter the conduct of the study. In addition, Pfizer announced plans to sponsor a clinical trial to assess celecoxib in OA patients at high-risk for cardiovascular disease.
Editorial Comment: These results are confusing and difficult to interpret. Celebrex has been on the market for about 6 years. Although it is a COX-2 drug, like Vioxx, and has the theoretical capacity for cardiovascular complications, the experience with the drug to date in vast numbers of patients has not disclosed an increased risk of cardiovascular complications. Some of the patients in the APC trial (see above) were on higher than approved doses of the drug which may, in part, explain the discrepancy in results between this trial and the PreSCP, the Alzheimers, and all the past studies that did not disclose an increase cardiovascular risk with Celebrex.