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J R Soc Med. 2006 July; 99(7): 336.
PMCID: PMC1484551

Miss, Mister, Doctor: Celecoxib

Caldwell et al. (March 2006, JRSM1) concluded that there was an increased risk of myocardial infarction with celecoxib. However, their meta-analysis was limited to preexisting data from six studies and no new information.

Other meta-analyses of case-controlled/cohort observational studies2 and clinical trials3 did not show increased risk of cardiovascular thromboembolic events with celecoxib compared with nonselective NSAIDs.

Based on their inclusion criteria, the authors could have included additional studies in their meta-analysis. Synopses of more than 50 celecoxib clinical studies including serious adverse events (SAE) and fatalities are available at the website [http://www.clinicalstudyresults.org].

The authors also queried differences in the reporting of cardiovascular events from the CLASS trial in a Food and Drug Administration briefing document4 and in a published paper.5 This is due to differences in analytical criteria. In the briefing documents, if the time of last dose of study medication was unavailable, time of last visit or laboratory test was utilized as a proxy. This analysis gave 13 cardiovascular deaths (celecoxib: 5, comparator NSAIDs: 8) occurring within 28 days ending treatment4. White et al. reported all cardiovascular deaths within 30 days of the end of treatment. Where the time that treatment was stopped was not available, it was assumed death occurred on study medication. This gave a total of 20 (celecoxib: 10, comparator NSAIDs: 10).5

The USA Food and Drug Administration and the European Medicines Agency, Europe, have conducted reviews of celecoxib safety, including data from all trials utilized by Caldwell et al. and concluded that celecoxib could continue to be marketed with appropriate warnings on cardiovascular risk. Only a properly powered, prospective clinical study can definitively assess the relative safety of nonselective NSAIDs and the COX-2 selective inhibitors. PRECISION (Prospective Randomized Evaluation of Celecoxib Integrated Safety versus Ibuprofen or Naproxen), a large clinical study meeting these requirements is currently in final stages of preparation.

Notes

Competing interests The authors are employees of Pfizer Inc.

References

1. Caldwell B, Aldington S, Weatherall M, Shirtcliffe P, Beasley R. Risk of cardiovascular events and celecoxib: a systematic review and meta-analysis. J R Soc Med 2006;99: 132-40 [PMC free article] [PubMed]
2. Hernandez-Diaz S, Varas-Lorenzo C, Garcia Rodriguez LA. Non-steroidal anti-inflammatory drugs and the risk of acute myocardial infarction. Basic Clin Pharmacol Toxicol 2006;98: 266-74 [PubMed]
3. Simon L, White W, MacDonald T, Pan S, Rosenstein R, Gaffney M. Cardiovascular safety of CELEBREX: a meta-analysis of 41 clinical studies in 44,308 patients. American College of Rheumatology (ACR) annual scientific meeting 12-17 November 2005. Atlanta: ACR, 2006
4. US Food and Drugs Administration CLASS Advisory Committee Briefing Document. [http://www.fda.gov/ohrms/dockets/ac/01/briefing/3677b1_01_searle.pdf] Accessed 15 May 2006
5. White WB, Faich G, Whelton A, et al. Comparison of thromboembolic events in patients treated with celecoxib, a cyclooxygenase-2 specific inhibitor, versus ibuprofen or diclofenac. Am J Cardiol 2002;89: 425-30 [PubMed]

Articles from Journal of the Royal Society of Medicine are provided here courtesy of Royal Society of Medicine Press