Abstract: Objective To provide reference for the rational clinical use of uric acid-lowering drugs given their potential cardiovascular risks using data from FAERS database. Methods The data on ADE with febuxostat, allopurinol, benzbromarone, probenecid, labrizine, and pregabalin as the main suspected drugs in FAERS database between First quarter 2004 and third quarter 2021 was extracted. The proportional reporting ratio method and Bayesian Confidence Propagation Neural Network were used for signal mining of cardiovascular risks. Univariate logistic regression was used to identify the risk factors in the process of drug administration while bioinformatics technology was used to predict potential mechanisms of cardiovascular risks. Results Febuxostat had a significant cardiovascular risk profile, mainly in the form of heart failure, ischemic heart disease and cardiac arrhythmias. Risk factor mining found that a patient's age, weight, dose administered, dosing period, and combination of drugs were all associated with cardiovascular risks of febuxostat. The potential mechanism of febuxostat cardiovascular risks involved neuroactive ligand-receptor interactions. ITGAM expression in the core target showed dose-dependent changes with febuxostat, which might be a potential target for cardiovascular risks of febuxostat. Conclusion Among the uric acid-lowering drugs, febuxostat has obvious cardiovascular risks, and the risk factors should be controlled during medication. The mechanism for cardiovascular risks may be related to the disruption of the neuroactive ligand-receptor interaction pathway of monocytes and the expression of ITGAM.

Key words: uric acid-lowering drugs, febuxostat, FAERS, cardiovascular risk