Massive meta analysis clarifies cardiovascular safety of celecoxib (Celebrex)

Main Category: Arthritis / Rheumatology
Article Date: 23 Nov 2005 - 3:00 PDT

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The COX-2 specific inhibitor celecoxib (Celebrex) is not associated with an increased risk of serious cardiovascular thrombotic events compared to placebo or NSAIDs, according to a meta-analysis of 41 clinical studies in 44,308 patients, reported at the American College of Rheumatology (ACR) 2005 Annual Scientific Meeting, San Diego, California (November 12-17th).

The meta analysis, reported by Dr Lee Simon, Associate Clinical Professor of Medicine at Harvard Medical School, evaluated the cardiovascular safety of celecoxib versus both placebo and nonselective (ns) NSAIDs.

Clinical trials included in the analysis lasted at least two weeks and included end points evaluating the incidence of heart attack, stroke and death and a composite sum of these three end points, explained Dr Simon, a former Division Director of the Arthritis, Analgesic & Ophthalmologic Drug Product Division at the Center for Drug Evaluation and Research, United States Food and Drug Administration.

The meta-analysis showed that patients taking celecoxib had no more risk for heart attack, stroke, or CV death combined than those given placebo or ns-NSAIDs.

There were no significant differences in the number of strokes among patients given celecoxib or placebo. However, there were significantly more strokes among patients taking ns-NSAIDs than those treated with celecoxib.

The number of heart attacks was numerically higher with celecoxib than with ns-NSAIDs. However, the difference was not statistically significant. When evaluated against people taking placebo, people taking celecoxib had no significant difference in the number of heart attacks.

"There were no cardiovascular signals that were any different to the active comparators. Celecoxib was no different to non selective drugs in terms of cardiovascular risk," he said. Comparators included placebo, naproxen, diclofenac, ibuprofen, loxoprofen, acetaminophen and ketoprofen.

Significantly fewer patients receiving celecoxib experienced hypertension or oedema compared with those receiving nonselective NSAIDs. Furthermore, the incidence of cardiac failure was numerically lower in the celecoxib group than in the nonselective NSAID group, he explained.

"In this large meta-analysis comprising studies of two weeks to three years duration involving patients with chronic conditions, celecoxib at doses of 200mg or more total daily dose was not associated with an increased risk of serious CV thromboembolic events compared with placebo or nonselective NSAIDs," Dr Simon concluded.

Dr Gail Cawkwell, Senior Medical Director, Arthritis, Pain and Musculoskeletal at Pfizer (the company that funded the meta analysis) said that the study was being prepared for publication in a peer reviewed journal, and the data had been shared with US and EU regulatory authorities.

"This analysis confirms once again that medicines like naproxen, ibuprofen and diclofenac have very similar rates of cardiovascular endpoints (combination of heart attack, stroke and cardiovascular deaths) compared to Celebrex. It is unfortunate that European labelling separates Celebrex from those medications. The US labelling reflects what has been shown by this meta analysis: that all these drugs have a similar cardiovascular safety profile, they all carry similar risks."

"All NSAIDs, selective and nonselective, carry similar levels of risk. We certainly feel there is a level playing field. Whatever risks people have been facing for decades with medicines such as ibuprofen, albeit unknowingly, are now a bit clearer, and that those risks are similar for a medicine like Celebrex."

There was further heartening news for celecoxib from an unrelated study reported at the ACR. The GAIT study (Abstract 622) compared the dietary supplements glucosamine and chondroitin sulphate (alone and in combination) against celecoxib in 1583 patients. Lead author Dr Daniel Clegg, University of Utah, said that there was no difference between placebo and the dietary supplements: only celecoxib reached the primary efficacy endpoint. Given concern over the cardiovascular safety of coxibs, Dr Clegg said that the FDA had asked for an interim safety analysis to see if there was any signal of cardiac problems in celecoxib- versus dietary-supplement treated patients. "There was no such signal, the treatment arms of the study had indistinguishable safety profiles," he said.

Reference

Simon LS, White WB, MacDonald TM, Pan S, Rosenstein RB, Gaffney M. Cardiovascular safety of celecoxib: A meta-analysis of 41 clinical studies in 44,300 patients. Abstract 1049, American College of Rheumatology annual meeting November 2005. Published in Arthritis and Rheumatism, Volume 52, No 9, 2005 page S406.

Written by: Ian Mason
ianmason@ntlworld.com