Systematic review and meta-analysis of the risk of major cardiovascular events with etoricoxib therapy.

OBJECTIVE To determine the risk of thromboembolic cardiovascular events associated with the use of etoricoxib, a COX-2 inhibitor. DESIGN Systematic review and meta-analysis of placebo-controlled randomised double-blind clinical trials of etoricoxib that were of at least 6 weeks duration and presented data on cardiovascular thromboembolic events. DATA SOURCES Six databases including Medline and EMBASE. METHODS The main outcome measure was cardiovascular thromboembolic events. A secondary analysis was undertaken to identify the presence or absence of predefined features that allowed determination of major cardiovascular events in a clinical trial. RESULTS There were five studies with a total of 2,919 subjects included in the meta-analysis. There were 7 cardiovascular thromboembolic events in 1,441 patients (0.5%) treated with etoricoxib, and 1 event in 906 patients (0.1%) on placebo. A pooled fixed effect estimate of the absolute risk difference was 0.5% (95% CI 0.1-1.0). The odds ratio for the risk of cardiovascular events with etoricoxib was 1.49 (0.42-5.31). CONCLUSION The clinical trials of etoricoxib provide limited data on major cardiovascular thromboembolic events as they were neither designed nor powered to assess the potential cardiovascular risks with etoricoxib therapy. However, the limited data that were available provide weak evidence of an increased cardiovascular risk with etoricoxib consistent with a class effect for COX-2 inhibitors.