Do selective COX-2 inhibitors increase the risk of cerebrovascular events? A meta-analysis of randomized controlled trials


Dr Darren Ashcroft, School of Pharmacy and Pharmaceutical Sciences, University of Manchester, Oxford Road, Manchester, M13 9PL, UK. Tel.: +44 161 275 4299; fax: +44 161 275 2416; e-mail:


Objectives:  To evaluate the risk of cerebrovascular events (CVEs) associated with selective cyclooxygenase-2 inhibitors (coxibs).

Method:  Systematic review and meta-analysis of randomized controlled trials (RCTs). A fixed-effect model was used to estimate the odds ratios (ORs) for risk of CVE associated with coxibs compared against placebo, non-selective non-steroidal anti-inflammatory drugs (NSAIDs) and other coxibs.

Results:  Forty trials (88 116 patients) were included in the meta-analysis. The overall pooled OR for CVE for any coxib against placebo was 1·03 (95% CI: 0·71, 1·50). Comparing individual coxibs against placebo, we found that celecoxib, rofecoxib, etoricoxib and lumiracoxib were associated with higher CVE risks and valdecoxib was associated with a lower CVE risk, although there were no significant differences detected. There was also no significant difference in risk of CVE when comparing coxibs against any non-selective NSAIDs; the corresponding pooled OR was 0·86 (95% CI: 0·64, 1·16).

Conclusion:  On the basis of a detailed analysis of available RCTs, there does not appear to be any significant difference in risk of CVEs associated with coxibs when compared against placebo or non-selective NSAIDs. It is likely that the increased risk of thrombotic vascular events associated with coxibs is largely attributable to an increased risk of myocardial infarction, rather than CVEs.