Risk of cardiovascular events and celecoxib: A systematic review and meta-analysis

Medical Research Institute of New Zealand, Wellington, NZ.
Journal of the Royal Society of Medicine (Impact Factor: 2.12). 04/2006; 99(3):132-40. DOI: 10.1258/jrsm.99.3.132
Source: PubMed


To examine whether the increased risk of cardiovascular events with rofecoxib represents a class effect of cyclooxygenase-2 (COX-2) specific inhibitors.
Systematic review and meta-analysis of randomized double-blind clinical trials of celecoxib of at least 6 weeks' duration and presented data on serious cardiovascular thromboembolic events. Data sources included six bibliographic databases, the relevant files of the United States Food and Drug Administration, and pharmaceutical company websites.
Pooled fixed effects estimates of the odds ratios for risk of cardiovascular events with celecoxib compared with comparator treatment were calculated using the inverse variance weight method. The main outcome measure was myocardial infarction.
Four placebo-controlled trials with 4422 patients were included in the primary meta-analysis comparing celecoxib with placebo. The odds ratio of myocardial infarction with celecoxib compared to placebo was 2.26 (95%confidence interval 1.0 to 5.1). For composite cardiovascular events [odd ratio 1.38 (95% CI 0.91 to 2.10)], cardiovascular deaths [OR 1.06 (95% CI 0.38 to 2.95)] and stroke [OR 1.0(95% CI 0.51 to 1.84)] there was no significant increase in risk with celecoxib. The secondary meta-analysis which included a total of six studies (with placebo, diclofenac, ibuprofen, and paracetamol as comparators) of 12 780 patients, showed similar findings with a significant increased risk with celecoxib for myocardial infarction [OR 1.88 (95% CI 1.15 to 3.08)] but not other outcome measures.
The available data indicate an increased risk of myocardial infarction with celecoxib therapy, consistent with a class effect for COX-2 specific inhibitors.

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    • "The equipotent dose for the treatment of acute pain is 400 mg of celecoxib/50 mg of rofecoxib. This would explain the differences between COX-2/COX-1 selectivity, and the differences found in the incidence of cardiovascular adverse effects, which are greater for rofecoxib [19] [20]. The decision to withdraw this drug from the US market in September 2004 was based on a three year controlled clinical trial on the prevention of adenomatous polyposis, in which an increased relative risk of cardiovascular effects such as ischemia or myocardial infarction was found in patients who were on treatment for more than 18 months. "
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    • "The publications showed that celecoxib induced fewer gastrointestinal ulcers than its competitors, but it was later revealed that the trials ran for longer than 6 months, and analyses done according to the trial protocol showed no advantage of celecoxib [34]. Despite the fact that only 16 out of at least 27 trials of celecoxib were included in the relevant FDA reports [36], independent researchers who had access to FDA data nevertheless substantiated the cardiovascular harms of celecoxib [37]. "
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