Celebrex Cardiovascular Safety Supported In FDA/Kaiser Study
This article was originally published in The Pink Sheet Daily
Executive Summary
FDA releases data from COX-2 cardiovascular safety study that was included in a Sept. 30 internal memo to Office of Drug Safety Director Seligman. The study shows Celebrex patients have lower cardiovascular safety risk compared to remote NSAID users.
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An FDA/Kaiser Permanente retrospective study conducted on NSAIDs and COX-2s supports the cardiovascular safety of Pfizer's Celebrex (celecoxib). The study, led by FDA Office of Drug Safety Associate Director for Science David Graham, MD, found a trend decrease in cardiovascular events among Celebrex patients compared to patients with remote exposure (treatment ending 60 days or more prior to the study) to non-steroidal anti-inflammatory drugs. A total of 126 acute myocardial infarction events were observed in patients taking Celebrex, for a relative risk compared to remote NSAID use of 0.86. To put this into perspective, study results showed ibuprofen and naproxen had relative risks of 1.09 and 1.18, respectively. Merck's Vioxx (rofecoxib)had a 1.29 relative risk at the lower dose (25 mg) and showed a 3.15-fold increase in risk at the higher dose (50 mg) compared to remote NSAID use. The study also showed a 1.5-fold increase in risk for Vioxx compared to Celebrex at the 25 mg dose and a 3.7-fold increase at the 50 mg dose. The study data were included in an 1 internal memo from Graham to Office of Drug Safety Acting Director Paul Seligman, MD. The report concludes with Graham's suggestion that both doses of Vioxx should be withdrawn (see 2 (Also see "FDA Memo Discussed Pulling Vioxx Based On HMO Study" - Pink Sheet, 3 Nov, 2004.)). The FDA memo is dated Sept. 30, the same day Merck announced the voluntary worldwide withdrawal of Vioxx (3 (Also see "FDA Has One Month To Mull Approval Of Merck's Arcoxia Following Vioxx Withdrawal" - Pink Sheet, 30 Sep, 2004.)). FDA said the timing was coincidental. FDA posted the memo on its website Nov. 2, and in a cover page stated that "the report has not been fully evaluated by the FDA and may not reflect official views of the agency. However, in light of the recent market withdrawal of Vioxx, FDA has decided to publicly release the document at this time." Initial results of the study were first presented at the International Conference on Pharmacoepidemiology & Therapeutic Risk Management in August (4 (Also see "FDA/Kaiser Study Questions Merck's Vioxx Cardiovascular Safety" - Pink Sheet, 25 Aug, 2004.)). Since the Vioxx withdrawal, there have been questions as to whether the cardiovascular safety profile should be considered a class effect. FDA Acting Deputy Commissioner of Operations Janet Woodcock, MD, recently said no cardiovascular safety signal has been seen so far in Celebrex ("5 (Also see "Celebrex Database Clear Of Cardiovascular Signals, FDA’s Woodcock Says" - Pink Sheet, 29 Oct, 2004.)). A study of Pfizer's follow-on COX-2 inhibitor Bextra (valdecoxib)showed an increased cardiovascular risk when used following coronary artery bypass graft surgery (6 (Also see "Pfizer Sees Increased Cardiovascular Risk With Bextra After Bypass Surgery" - Pink Sheet, 15 Oct, 2004.)). - Lee Kalowski |