The Role of Xanthine Oxidase Inhibitors in Patients with History of Stroke: A Systematic Review

Background: Xanthine oxidase inhibitors are commonly used to lower uric acid levels in patients with gout. Due to their effects on endothelial function, they have also been investigated for possible benefits for patients with cardiovascular disease. Objective: To assess the efficacy and safety of xanthine oxidase inhibitors in the treatment of patients with history of stroke. Methods: MEDLINE (1946-June 2017) and EMBASE (1947-June 2017) were queried using the search terms: “allopurinol” OR “febuxostat” OR “xanthine oxidase inhibitor” OR “xanthine oxidase/ antagonists and inhibitors” AND “stroke” OR “cerebral infarction” OR “cerebrovascular accident”. Studies appropriate to the objective were evaluated, including five randomized, placebo-controlled, double-blind trials investigating the effect of allopurinol in patients with history of stroke. No articles evaluating the use of febuxostat in this setting were identified. Results: In patients with history of stroke, treatment with allopurinol resulted in improvements in several markers of endothelial function, inflammatory markers, and scores on the Modified Rankin Scale. Study durations ranged from 6 weeks to 1 year, and studies used varying doses of allopurinol. Allopurinol was well tolerated in most studies, with some reports of gastrointestinal adverse effects, headache and rash. Conclusion: Based on the reviewed literature, allopurinol appears to be a promising therapy to improve vascular function and reduce disability in patients who have had a stroke. The benefits seen are in combination with current standard of care treatments with aspirin and lipid-lowering therapy. Larger trials are necessary to better understand the role of allopurinol in patients with history of stroke. Keywords: Allopurinol, stroke, cerebrovascular disease, vascular endothelium, febuxostat, secondary prevention, uric acid.