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Evidence summaries

Selective and Traditional Non-Steroidal Anti-Inflammatory Drugs and the Risk of Atherothrombosis

Selective COX 2 inhibitors are associated with a moderate increase in the risk of vascular events, as are high dose regimens of ibuprofen and diclofenac, but high dose naproxen is not associated with such an excess. Level of evidence: "A"

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.

    References

    • Kearney PM, Baigent C, Godwin J, Halls H, Emberson JR, Patrono C. Do selective cyclo-oxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis? Meta-analysis of randomised trials. BMJ 2006 Jun 3;332(7553):1302-8. [PubMed]

Primary/Secondary Keywords