Use of first- and second-generation cyclooxygenase-2 selective nonsteroidal antiinflammatory drugs and risk of acute myocardial infarction

Background: The cardiovascular safety of cyclooxygenase (COX)-2-selective nonsteroidal antiinflammatory drugs (NSAIDs) has come under scrutiny after the withdrawal of rofecoxib and halting of the Adenoma Prevention with Celecoxib trial. Whether the newer second-generation COX-2 inhibitors (etoricoxib, valdecoxib) also increase the cardiovascular risk is unknown. Methods and Results: We performed a nested case-control study in a cohort of 486 378 persons registered within the United Kingdom General Practice Research Database with at least 1 prescription of an NSAID between June 1, 2000, and October 31, 2004. A total of 3643 cases with acute myocardial infarction ( AMI) were matched to 13 918 controls on age, sex, year of cohort entry, and general practice. Rate ratios (RRs) of AMI associated with use of COX-2-selective and -nonselective NSAIDs were calculated. Current use of etoricoxib was associated with a 2.09-fold (95% confidence interval [CI], 1.10 to 3.97) risk of AMI compared with no use of NSAIDs during the prior year. Current use of rofecoxib (RR = 1.29; 95% CI, 1.02 to 1.63), celecoxib (RR = 1.56; 95% CI, 1.22 to 2.00), and diclofenac (RR = 1.37; 95% CI, 1.17 to 1.59) also significantly increased the AMI risk. For current use of valdecoxib, the RR was 4.60 (95% CI, 0.61 to 34.51). RRs appeared to increase with higher daily doses of COX-2 inhibitors and were also increased in patients without major cardiovascular risk factors. Conclusions: Our study supports the hypothesis that the elevated risk of AMI is a class effect of COX-2 inhibitors. The increase in risk appears to be dose dependent, but further data are needed to verify this observation.