One hundred and thirty-eight RCTs (n=145,373) were included in the review.
Selective COX-2 inhibitors versus placebo.
Of the 121 trials, 216 vascular events occurred during 18,490 person-years of exposure to COX-2 inhibitors. COX-2 inhibitors were associated with a 42% relative increase in the incidence of a serious vascular event (RR 1.42, 95% CI: 1.13, 1.78); this was largely due to an increased risk of MI (RR 1.86, 95% CI: 1.33, 2.59). No significant heterogeneity was found between the different selective COX-2 inhibitors. No statistically significant differences between the groups were demonstrated for the incidence of stroke or vascular death.
When only long-term trials (1 year or more) were analysed (9 trials), little difference in the point estimate was shown (RR 1.45, 95% CI: 1.12, 1.89). There was a trend towards an increased incidence of serious vascular events with celecoxib. There were insufficient data to investigate the effect of dose on event rate for the other COX-2 inhibitors. No significant difference between RRs was shown when concomitant use of aspirin was considered.
Selective COX-2 inhibitor versus traditional NSAIDs.
There was no statistically significant difference in the rate of a serious vascular event between participants receiving COX-2 inhibitors and any NSAID (RR 1.16, 95% CI: 0.97, 1.38), based on 91 trials; significant heterogeneity was shown.
When compared with naproxen, selective COX-2 inhibitors were associated with an increase in the incidence of a serious vascular event (RR 1.57, 95% CI: 1.21, 2.03) and MI (RR 2.04, 95% CI: 1.41, 2.96). No significant difference in the incidence of stroke or vascular death was found. No statistically significant difference was found between any selective COX-2 inhibitor and non-naproxen NSAID on the incidence of a serious vascular event (RR 0.88, 95% CI: 0.69, 1.12), MI (RR 1.20, 95% CI 0.85, 1.68) or vascular death (RR 0.67, 95% CI: 0.43, 1.06). Selective COX-2 inhibitors were shown to significantly reduce the incidence of stroke in comparison with other non-naproxen NSAIDs (RR 0.62, 95% CI: 0.41, 0.95).
Traditional NSAIDs versus placebo.
Indirect comparisons demonstrated a non statistically significant increased risk of vascular events for ibuprofen, and a statistically significant increase in risk for diclofenac. A reduction in the incidence of vascular events was found for naproxen. No information on how many trials these comparisons were based was provided.