Selectivity of NSAIDs for COX-2 and cardiovascular outcome

Nonsteroidal anti-inflammatory drugs (NSAIDs) with increased selectivity for the cyclooxygenase-2 (COX-2) isoform reduce gastrotoxicity but may increase adverse cardiovascular events.

We searched the literature for studies that reported the odds ratio (OR) for such events following exposure to NSAIDs.

For studies comparing NSAID use with no use, increased COX-2 selectivity was significantly related to cardiovascular risk (log OR) amongst observational studies (R = -0.34, P < 0.001) and randomized controlled trials (RCTs) (R = -0.56, P < 0.001). For studies comparing NSAIDs, difference in selectivity was related to risk for observational studies (R = -0.28, P = 0.005) but not for RCTs (R = -0.23, P = 0.15).

Although increased COX-2 selectivity may reduce gastrotoxicity, this may be at the cost of increasing cardiovascular risk.