The Effect of Xanthine Oxidase Inhibition Upon Ejection Fraction in Heart Failure Patients: La Plata Study

Abstract 

Background

Reactive oxygen species (ROS) have been linked to hypertrophy, remodeling and abnormal excitation-contraction coupling. Previous data demonstrated that an increase in oxidative stress is associated to the pathogenesis of congestive heart failure (CHF). We examined whether inhibition of the superoxide anion (·O₂⁻)-generating enzyme xanthine oxidase (XO) with oxypurinol may improve cardiac function in patients with CHF.

Methods and Results

A randomized, placebo-controlled, double-blind study on 60 patients (30/group) with New York Heart Association class II-III CHF, comparing 600-mg/day oxypurinol during 1 month with placebo, added to standard therapy. Effects on left ventricular ejection fraction (LVEF), serum uric acid (SUA) level, and 6-minute walking test were analyzed. SUA decreased by 16.0 ± 2.8 mg/L from baseline to Week 4 in the oxypurinol group relative to placebo (P < .01, n = 30 per group). LVEF showed an increase of 4.7 ± 2.6% from baseline to Week 4 in the oxypurinol group relative to placebo that did not reach statistical significance (P < .08). When patients with LVEF >40% at baseline were excluded, a statistically significant increase of 6.8 ± 2.8% from baseline to Week 4 was seen in the oxypurinol group relative to placebo (P < .02, n = 26 placebo, n = 21 oxypurinol). No treatment-related adverse effects or increase in walking capacity were detected.

Conclusion

Inhibition of XO by oxypurinol in patients with CHF decreases SUA and improves LVEF in patients with LVEF ≤40% after 1 month of treatment.

Key Words: Heart failure, Trials, Left ventricular ejection fraction, Xanthine oxidase inhibition, Uric acid