Abstract / Summary
Abstract Background Hyperuricaemia is a potentially modifiable risk factor for cardiovascular disease. Xanthine oxidase inhibition via allopurinol may reduce oxidative stress and improve vascular function, however its role in cerebrovascular disease is unclear. Given the overlap in pathophysiology, allopurinol may mitigate secondary injury following stroke. Methods A systematic review was conducted in accordance with PRISMA guidelines and prospectively registered with PROSPERO. We searched PubMed, Scopus, and CENTRAL from inception to 1st January 2026 for studies evaluating uric acid-lowering therapies in adult stroke populations. Eligible studies evaluated clinical, biochemical, vascular, or neuroimaging outcomes. Meta-analysis was not performed due to heterogeneity. Risk of bias and certainty were assessed using study-specific validated tools. Results Six eligible trials, all evaluating allopurinol in predominantly ischaemic stroke populations, were included. Allopurinol dose (100–600 mg/day), treatment duration (6-104 weeks), and timing (< 24 hours to several years post-stroke) varied substantially. No consistent benefit was observed for neurological impairment, recurrence, or mortality. Early treatment was associated with dose-dependent reductions in endothelial activation, while other studies demonstrated improvements in vascular measures potentially independent of urate reduction. Subacute and chronic trials found no effect on cerebrovascular reactivity or white matter hyperintensity progression. Conclusions Xanthine oxidase inhibition with allopurinol demonstrates heterogeneous biological and vascular effects following stroke, without consistent clinical benefit. Any therapeutic signal appears concentrated in studies evaluating earlier treatment initiation, without definitive conclusions regarding optimal timing or dose. Current evidence does not support routine allopurinol use following stroke but may indicate a plausible early therapeutic window for further investigation.