Celebrex doubles the risk of MI, meta-analysis indicates
Last Updated: 2006-03-01 8:10:26 -0400 (Reuters Health)
LONDON (Agence de Presse Medicale for Reuters Health) - Pfizer's Celebrex (celecoxib) doubles the risk of a myocardial infarction compared with placebo and is consistent with a class effect for COX-2 inhibitors, according to research published on Wednesday in the journal of the UK's Royal Society of Medicine.
"Our evidence shows an increased risk of heart attack in patients taking celecoxib," said Professor Richard Beasley, of New Zealand's Medical Research Institute in Wellington and colleagues.
The meta-analysis of four studies (4,422 patients) comparing celecoxib with placebo found the odds ratio of MI compared to placebo was 2.26 (95% CI, 1.0 to 5.1).
A secondary meta-analysis that included a further two trials (total 12,780 patients) which added diclofenac, ibuprofen or paracetamol as comparators produced a "similar" MI odds ratio of 1.88 (95% CI, 1.15 to 3.08).
The authors say the results correspond with an earlier meta-analysis showing a 2.24 fold increase in the risk of heart attack associated with Vioxx (rofecoxib), as well as data showing an increased risk in other COX-2 inhibitors.
Although Merck and Co's Vioxx (rofecoxib) has been withdrawn worldwide, regulators have allowed Celebrex to remain on the market. The study authors say this may have been an error.
"This systematic review and meta analyses provide evidence of an increased risk of myocardial infarction associated with the use of celecoxib, consistent with a class effect of COX-2 inhibitors," they write. "This finding would suggest that the preferential risk/benefit assessment afforded celecoxib over other COX-2 inhibitors by the FDA may not be supported by the currently available data."
To be included in the analysis, trials had to be of at least 6 weeks' duration and to report data on cardiovascular thromboembolic events.
In the smaller analysis there were 29 MIs among the 2,574 patients on Celebrex (1.13%) compared to 6 among the 1447 (0.41%) in the placebo group.
In the larger study there were to 55 infarctions among 6,658 (0.83%) in the celecoxib group compared to 21 in 5,522 (0.38%) receiving control treatments.
The researcher's noted that neither of the meta-analyses showed a significant increase in composite cardiovascular events, cardiovascular deaths or stroke.
They said the lack of corresponding cerebrovascular events was a similar pattern to that shown by rofecoxib but was not shown by parecoxib or valdecoxib (Pfizer's Dynastat and Bextra).
"This finding suggests that the proposed mechanism whereby COX-2 inhibitors increase the cardiovascular risk, by shifting the functional balance of the vasoactive prostanoids, may preferentially apply to the pathogenesis of myocardial infarction rather than cerebrovascular events.
"This may be because myocardial infarction is predominantly due to thrombosis within the coronary arteries, whereas two-thirds of cerebrovascular events are due to thromboembolism from sources outside the brain."
Earlier this week, a study being published in the March issue of the American Journal of Medicine concluded that short-term use of Celebrex was not linked to a higher risk of heart attacks than traditional NSAIDS. (See Reuters Health report, "Large study documents short-term safety of celecoxib for osteoarthritis"; 2006-02-27 8:48:10.)
J R Soc Med 2006;99:132-140
