The Pharmaceutical Journal
Vol 276 No 7390 p256
4 March 2006

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Celecoxib doubles risk of MI

Treatment with celecoxib (Celebrex) doubles the risk of myocardial infarction compared with placebo, the authors of a meta-analysis suggest this week (Journal of the Royal Society of Medicine 2006;99:132).

The researchers conducted a systematic review and meta-analysis of randomised double-blind clinical trials of at least six weeks’ treatment with celecoxib and which presented data on serious cardiovascular thromboembolic events. Data from four trials involving 4,422 patients were examined.

The researchers calculated that the odds ratio of myocardial infarction in patients taking celecoxib, compared with those taking placebo, was 2.26 (95 per cent confidence interval 1.0–5.1).

“This meta-analysis provides evidence that the use of celecoxib, the most commonly prescribed cyclo-oxygenase-2 specific inhibitor, is associated with an increased risk of myocardial infarction. While this finding is limited by the small number of clinical trials of celecoxib that reported outcomes, it is consistent with a class effect of COX-2 specific inhibitors increasing the risk of myocardial infarction,” the authors say.

However, a spokesman for Pfizer, manufacturer of Celebrex, said that the authors’ conclusions were not applicable to the drug as used within its licensed indications. Celebrex is licensed for a maximum dose of 200mg for osteoarthritis or 400mg for rheumatoid arthritis, but the trials included patients on 800mg doses, he explained. The number of patients involved in the meta-analysis was relatively small, he added, and larger numbers of patients would need to be pooled to form reliable conclusions.

In addition, a study of the efficacy and gastro-intestinal safety of celecoxib, published last month, included a post-hoc analysis of cardiovascular event rates and found no statistical difference between the number of cardiovascular events reported for celecoxib and the comparator groups (American Journal of Medicine 2006;119:255). However, the authors acknowledge that the numbers of events were low and the study was not powered to detect such differences.

In response to the latest research, the Medicines and Healthcare products Regulatory Agency said: “This new study is based on data already assessed by regulatory agencies within Europe. The finding of the authors is entirely consistent with the conclusions of the former Committee on Safety of Medicines and the European Medicines Agency, who reviewed the cardiovascular safety of the selective COX-2 inhibitors in 2005.” Following the review, the CSM and EMEA issued updated advice on the use of selective COX-2 inhibitors.

They recommended that patients treated with COX-2 inhibitors who have established ischaemic heart disease or cerebrovascular disease should be switched to non-coxib treatment and that, for all other patients, treatment should be individully assessed for risks and benefits (PJ, 26 February 2005, p228).