Beyond pain relief: the thrombosis threat of celecoxib.

Background: There are still some points of controversy regarding the adverse events associated with celecoxib use, particularly in terms of thrombosis. Objectives: To explore the relationship between celecoxib and thrombosis in the real world and to investigate the causality that exists. Design: We conducted pharmacovigilance analysis on spontaneously reported adverse events to evaluate the association between celecoxib and thrombotic events. In addition, Mendelian randomization studies of drug targets were used to explore the causal relationship between them. Methods: This study used the data from the United States Food and Drug Administration Adverse Event Reporting System (FAERS), the Japanese Adverse Drug Event Report database, and the Canada Vigilance Adverse Reaction (CVAR) for pharmacovigilance analysis. Among these, the Report Odds Ratio, Proportional Reporting Ratio, Information Component, and Empirical Bayesian Geometric Mean were used to determine the strength of adverse event signals. In addition, the Weibull shape parameter test was used in this study to investigate the trend of adverse events. Mendelian randomization was used to explore the causal link between celecoxib and deep vein thrombosis. Results: Pharmacovigilance signals indicated that celecoxib was associated with an increased risk of thrombosis, with deep vein thrombosis demonstrating positive signals in all three populations. In addition, Mendelian randomization analyses provided evidence to support a causal relationship between celecoxib and deep vein thrombosis and clarified that carbonic anhydrase 2, a target protein of celecoxib, is causally linked to deep vein thrombosis. Conclusion: The use of celecoxib leads to an increased risk of thrombosis and suggests a causal relationship.