The effect of xanthine oxidase inhibition upon ejection fraction in heart failure patients: La Plata Study.
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.


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.


CONCLUSIONS
Inhibition of XO by oxypurinol in patients with CHF decreases SUA and improves LVEF in patients with LVEF < or = 40% after 1 month of treatment.
Cingolani
Horacio E
HE
Centro de Investigaciones Cardiovasculares, Consejo Nacional de Investigaciones Científicas y Técnicas, Universidad Nacional de La Plata, Argentina.
Plastino
Juan A
JA
Escudero
Eduardo M
EM
Mangal
Brian
B
Brown
Joanne
J
Pérez
Néstor G
NG
D000368:Aged; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology*; D006801:Humans; D008297:Male; D010117:Oxypurinol / Q000627:therapeutic use*; D010807:Physical Endurance; D013318:Stroke Volume / Q000187:drug effects*; D014527:Uric Acid / Q000097:blood; D016138:Walking; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; D014527:Uric Acid; D014969:Xanthine Oxidase; D010117:Oxypurinol