Risk of ischemic stroke in benzbromarone versus allopurinol users: a real-world cohort study using TriNetX

To investigate whether benzbromarone or allopurinol use is associated with the risk of ischemic stroke among individuals aged 20-84 years with hyperuricemia or gout.

We conducted a retrospective cohort study utilizing 2006 to 2024 records from the TriNetX network. Individuals aged 20-84 years who used benzbromarone or allopurinol were included. To form the benzbromarone and allopurinol groups, individuals were matched 1:1 based on demographic and clinical comorbidities. The unadjusted risk ratio was estimated using the Compare Outcomes module in TriNetX. Additionally, a Cox proportional hazards regression model was applied to the unmatched cohort to estimate the adjusted hazard ratio, controlling for demographic and clinical comorbidities.

After matching, each group included 26,510 individuals. Over a maximum 15-year follow-up period, the cumulative incidence of ischemic stroke was 1.375% in the benzbromarone group and 1.179% in the allopurinol group. The unadjusted risk ratio was 1.166 (95% CI: 1.003-1.355). The adjusted hazard ratio from the Cox model was 1.296 (95% CI: 1.129-1.488; P = 0.0002), indicating a statistically significant increased risk of ischemic stroke associated with benzbromarone use compared to allopurinol.

Benzbromarone use was associated with a higher long-term risk of ischemic stroke compared to allopurinol among individuals aged 20-84 years with hyperuricemia or gout. Key Points What is known: • Benzbromarone and allopurinol are two commonly prescribed urate-lowering therapies for hyperuricemia and gout. • The association between these medications and the risk of ischemic stroke remains uncertain. What is new here: • In this study, benzbromarone use was associated with a significantly higher risk of ischemic stroke compared to allopurinol use. • The adjusted hazard ratio for ischemic stroke was 1.296 (95% CI: 1.129-1.488, P = 0.0002) for benzbromarone versus allopurinol. Translational impact: • These findings suggest that benzbromarone may carry a higher long-term ischemic stroke risk than allopurinol, which could inform clinical decision-making in urate-lowering therapy selection.