Allopurinol therapy improves vascular endothelial function in subjects at risk for cardiovascular diseases: a meta‐analysis of randomized controlled trials

Summary Aims The effect of allopurinol on flow‐mediated dilation (FMD), an index of endothelial function in humans, remains inconsistent. We performed a meta‐analysis to determine whether allopurinol therapy could improve FMD. Methods Human intervention studies were identified by systematic searches of Medline, Embase, Cochrane's library, and references of related reviews and studies. A random‐effect model was applied to estimate the pooled results. Results Ten randomized controlled trials with 594 subjects at risk of cardiovascular risks were included. Results of the meta‐analysis indicated that allopurinol therapy significantly improved FMD in these subjects as compared with control groups (WMD=1.67%, 95% CI: 0.83% ~ 2.50%, P<.001; I2=86%), with no evidence of significant heterogeneity if only double‐blinded studies were included (WMD=1.36%, 95% CI: 0.89% ~ 1.83%, P<.001; I2=21%). Results of metaregression and subgroup analyses suggested that the benefit of allopurinol to FMD seemed to be not related to its uric acid (UA)‐lowering action. Moreover, allopurinol therapy may be associated with more remarkable improvement of FMD in subjects with lower serum UA (<7 mg/dL: WMD=2.62%, 95% CI: 1.10% ~ 4.14%), compared to those with higher UA (≥7 mg/dL: WMD=0.87%, 95% CI: 0.37% ~ 1.38%; P for subgroup difference=.03). Conclusions Allopurinol therapy is associated with significantly improved endothelial function in subjects at risk of CVD risks, and the beneficial effects of allopurinol seemed to be more remarkable in patients with normal UA at baseline.