A meta-analysis 1 included 138 randomised trials involving a comparison of a selective COX 2 inhibitor versus placebo or versus a traditional NSAID (or both), with a total of 145 373 subjects.
In placebo comparisons, allocation to a selective COX 2 inhibitor was associated with a 42% relative increase in the incidence of serious vascular events (1.2%/year v 0.9%/year; rate ratio 1.42, 95% confidence interval 1.13 to 1.78; p=0.003). There was no significant heterogeneity among the different selective COX 2 inhibitors. The increase was chiefly attributable to an increased risk of myocardial infarction (0.6%/year v 0.3%/year; rate ratio 1.86, 95% CI 1.33 to 2.59; p=0.0003), with little apparent difference in other vascular outcomes.
Overall, the incidence of serious vascular events was similar between a selective COX 2 inhibitor and any traditional NSAID (1.0%/year v 0.9%/year; rate ratio 1.16, 95% CI 0.97 to 1.38; p=0.1). Statistical heterogeneity (p=0.001) was found between trials of a selective COX 2 inhibitor versus naproxen (rate ratio 1.57, 95% CI 1.21 to 2.03) and of a selective COX 2 inhibitor versus non-naproxen NSAIDs (rate ratio 0.88, 95% CI 0.69 to 1.12). The summary rate ratio for vascular events, compared with placebo, was 0.92 (0.67 to 1.26) for naproxen, 1.51 (0.96 to 2.37) for ibuprofen, and 1.63 (1.12 to 2.37) for diclofenac.
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