Cardiovascular thromboembolic events associated with febuxostat: investigation of cases from the FDA adverse event reporting system database.

OBJECTIVE

Uloric (Febuxostat) has been linked with cardiovascular thromboembolic events in gout patients. However, no post-marketing data analysis has investigated these drug-associated adverse event reports. The study objective was to identify febuxostat-associated cardiovascular thromboembolic event reports in the US using the Food and Drug Administration adverse event reporting system (AERS) database.

METHODS

Reports listing uloric and febuxostat as the suspect drug and cardiovascular thromboembolic events (combined in a single term based on adverse event reports of myocardial infarction, stroke, among others) as the adverse event were extracted from the drug's approval date through the fourth quarter of 2011. Bayesian statistics within the neural network architecture was implemented to identify potential signals of febuxostat-associated cardiovascular thromboembolic events. A potential signal for the drug-adverse event combination reports is generated when the lower limit of the 95% two-sided confidence interval of the information component (IC), denoted by IC025 is greater than zero.

RESULTS

Twenty-one combination reports of febuxostat-associated cardiovascular thromboembolic events were identified in gout patients in the US. The mean age of combination cases was 64 years. Potential signals (IC025 = 4.09) was generated for combination reports of febuxostat-associated cardiovascular thromboembolic events.

CONCLUSION

AERS indicated potential signals of febuxostat-associated cardiovascular thromboembolic events. AERS is not capable of establishing the causal link and detecting the true frequency of an adverse event associated with a drug. The positive IC value found in this study merits continued surveillance and assessment of cardiovascular thromboembolic events associated with Febuxostat.