CENTRO DE INVESTIGACIONES CARDIOVASCULARES "DR. HORACIO EUGENIO CINGOLANI"
Unidad Ejecutora - UE
The Effect of Xanthine Oxidase Inhibition Upon Ejection Fraction in Heart Failure Patients: La Plata Study.
CINGOLANI HE; PLASTINO JA; ESCUDERO EM; MANGAL B; BROWN J; PÉREZ NG
JOURNAL OF CARDIAC FAILURE
Año: 2006 vol. 12 p. 491 - 498
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: 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 one month to placebo, added to standard therapy. Effects on left ventricular ejection fraction (LVEF), serum uric acid (SUA) level and six-minute walking test were analyzed. Results: SUA decreased by 16.0±2.8mg/L from baseline to week four in the oxypurinol group relative to placebo (P<0.01, n=30 per group). LVEF showed an increase of 4.7±2.6% from baseline to week four in the oxypurinol group relative to placebo that did not reach statistical significance (P<0.08). When patients with LVEF>40% at baseline were excluded, a statistically significant increase of 6.8±2.8% from baseline to week four was seen in the oxypurinol group relative to placebo (P<0.02, n=26 placebo, n=21 oxypurinol). No treatment-related adverse effects or increase in walking capacity were detected. Conclusions: Inhibition of XO by oxypurinol in patients with CHF decreases SUA and improves LVEF in patients with LVEF£40% after one-month treatment.