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
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.