Do selective COX-2 inhibitors increase the risk of cerebrovascular events? A meta-analysis of randomized controlled trials.
OBJECTIVE
To evaluate the risk of cerebrovascular events (CVEs) associated with selective cyclooxygenase-2 inhibitors (coxibs).


METHODS
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).


CONCLUSIONS
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.
Chen
L-C
LC
School of Pharmacy and Pharmaceutical Sciences, University of Manchester, Oxford Road, Manchester, M13 9PL, UK.
Ashcroft
D M
DM
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects*; D006801:Humans; D009288:Naproxen / Q000009:adverse effects; D016032:Randomized Controlled Trials as Topic; D012306:Risk; D020521:Stroke / Q000139:chemically induced*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D009288:Naproxen