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

Abstract

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.