Cyclooxygenase-2 inhibitors and cardiovascular risk in a nation-wide cohort study after the withdrawal of rofecoxib

The use of selective cyclooxygenase (COX)-2 inhibitors (coxibs) has been associated with an increased cardiovascular risk. The aim of the present study was to evaluate the association of coxib use and future risk of cardiovascular events in a population-based cohort followed after the warnings concerning the cardiovascular safety of this class of drugs were issued. A nation-wide, population-based cohort of 7 million subjects, integrating data from the Prescribed Drug, Patient, Cause of Death, Income, Educational and Emigration Registers, was followed from 1 July 2005 to 31 December 2008. Analyses were performed for different cardiovascular outcomes in the whole population after exclusion of individuals with prior cardiovascular diagnosis (incident primary cardiovascular events; sample size, n 6 991 645). Cox proportional hazard ratios (HRs) revealed no significant association of coxib use with risk for myocardial infarction, ischaemic stroke, or heart failure. In contrast to these findings, coxib use was associated with an increased risk for a first episode of atrial fibrillation [HR 1.16; 95 confidence interval (CI) 1.051.29]. A post hoc analysis for different coxibs revealed a significant association with incident atrial fibrillation for etoricoxib (HR 1.35; 95 CI 1.191.54) but not for celecoxib (HR 0.94; 95 CI 0.791.11). Whereas safety measures appear to have limited serious cardiovascular consequences of COX-2 inhibitors, the risk of developing atrial fibrillation may have been overlooked and may necessitate consideration and precautions.