Celecoxib and Cardiac Abnormalities: a Biostatistical Analysis of Adverse Side Effects

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Celecoxib is a member of the coxib class of inhibitors that selectively inhibits COX‐2 over COX‐1. The withdrawal of rofecoxib (Vioxx) and valdecoxib (Bextra) due to severe cardiovascular complications has highlighted the importance of both pharmacological and epidemiological post‐market surveillance of this class of drugs. Previous work in our laboratory has shown that celecoxib can cause arrhythmic Drosophila heartbeat and the arrhythmic beating of rat heart cells in culture. This occurs via a mechanism that is independent of COX‐2 inhibition. Also, celecoxib inhibits the delayed rectifier potassium channel (KV2) in Drosophila and in rat heart cells, and the hERG potassium channels expressed in HEK‐293 cells. Since drug inhibition of hERG channels leads to cardiac arrhythmia in humans, it is important to examine clinical implications of the inhibition of these channels by celecoxib. We reviewed quarterly reports of celecoxib‐associated adverse events submitted to the United States Food and Drug Administration's (FDA) Adverse Events Reporting System over an eight‐year period. Data mining algorithms were developed to ascertain the number of celecoxib users and non‐users and the number of individuals in each group experiencing dysfunction of cardiac rhythm. We found that there was a statistically significant increase (unpaired t‐test p < 0.00001) of reported adverse events for those taking celecoxib (N= 48,824; 6.250%) compared to those not taking the drug (N= 3,600,644; 4.281%).